Therapeutic options for the management of severe COVID-19: A rheumatology perspective

array:23 ["pii" => "S2173574320301337" "issn" => "21735743" "doi" => "10.1016/j.reumae.2020.05.002" "estado" => "S300" "fechaPublicacion" => "2021-10-01" "aid" => "1425" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología" "copyrightAnyo" => "2020" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Reumatol Clin. 2021;17:431-6" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S1699258X2030108X" "issn" => "1699258X" "doi" => "10.1016/j.reuma.2020.05.002" "estado" => "S300" "fechaPublicacion" => "2021-10-01" "aid" => "1425" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Reumatol Clin. 2021;17:431-6" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "es" => array:12 [ "idiomaDefecto" => true "cabecera" => "Artículo especial" "titulo" => "Opciones terapéuticas en el manejo de la COVID-19 grave: una perspectiva de Reumatología" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "431" "paginaFinal" => "436" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Therapeutic Options for the Management of Severe COVID-19: A Rheumatology Perspective" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Claudia Mendoza-Pinto, Mario García-Carrasco, Pamela Munguía Realpozo, Socorro Méndez-Martínez" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Claudia" "apellidos" => "Mendoza-Pinto" ] 1 => array:2 [ "nombre" => "Mario" "apellidos" => "García-Carrasco" ] 2 => array:2 [ "nombre" => "Pamela" "apellidos" => "Munguía Realpozo" ] 3 => array:2 [ "nombre" => "Socorro" "apellidos" => "Méndez-Martínez" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2173574320301337" "doi" => "10.1016/j.reumae.2020.05.002" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574320301337?idApp=UINPBA00004M" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1699258X2030108X?idApp=UINPBA00004M" "url" => "/1699258X/0000001700000008/v1_202109290644/S1699258X2030108X/v1_202109290644/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2173574320300678" "issn" => "21735743" "doi" => "10.1016/j.reumae.2020.06.003" "estado" => "S300" "fechaPublicacion" => "2021-10-01" "aid" => "1395" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología" "documento" => "simple-article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Reumatol Clin. 2021;17:437-9" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "Brief Report" "titulo" => "Psoriasis induced by biological therapy" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "437" "paginaFinal" => "439" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Psoriasis inducida por terapia biológica" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 451 "Ancho" => 1250 "Tamanyo" => 96477 ] ] "descripcion" => array:1 [ "en" => "Images of palmoplantar psoriasis in a patient under treatment with anti-TNF." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Lydia Montolio Chiva, Àngels Martínez Ferrer, Almudena Mateu Puchades, Cristina Campos Fernández, Javier Narváez Garcia, Juan José Alegre Sancho" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Lydia" "apellidos" => "Montolio Chiva" ] 1 => array:2 [ "nombre" => "Àngels" "apellidos" => "Martínez Ferrer" ] 2 => array:2 [ "nombre" => "Almudena" "apellidos" => "Mateu Puchades" ] 3 => array:2 [ "nombre" => "Cristina" "apellidos" => "Campos Fernández" ] 4 => array:2 [ "nombre" => "Javier" "apellidos" => "Narváez Garcia" ] 5 => array:2 [ "nombre" => "Juan José" "apellidos" => "Alegre Sancho" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S1699258X2030019X" "doi" => "10.1016/j.reuma.2019.12.005" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1699258X2030019X?idApp=UINPBA00004M" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574320300678?idApp=UINPBA00004M" "url" => "/21735743/0000001700000008/v1_202110061021/S2173574320300678/v1_202110061021/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "Special Article" "titulo" => "Therapeutic options for the management of severe COVID-19: A rheumatology perspective" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "431" "paginaFinal" => "436" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Claudia Mendoza-Pinto, Mario García-Carrasco, Pamela Munguía Realpozo, Socorro Méndez-Martínez" "autores" => array:4 [ 0 => array:3 [ "nombre" => "Claudia" "apellidos" => "Mendoza-Pinto" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 1 => array:4 [ "nombre" => "Mario" "apellidos" => "García-Carrasco" "email" => array:1 [ 0 => "mgc30591@yahoo.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 2 => array:3 [ "nombre" => "Pamela" "apellidos" => "Munguía Realpozo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Socorro" "apellidos" => "Méndez-Martínez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Unidad de Investigación de Enfermedades Autoinmunes Sistémicas, Hospital de Especialidades, UMAE-Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Puebla, Mexico" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Reumatología e Inmunología, Facultad de Medicina, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Coordinación de Investigación en Salud, Delegación Puebla, Instituto Mexicano del Seguro Social, Puebla, Mexico" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Opciones terapéuticas en el manejo de la COVID-19 grave: una perspectiva de Reumatología" ] ] "textoCompleto" => "IntroductionThe degree of disease severity with COVID-19 varies and can become fulminant or fatal. The World Health Organization (WHO) estimates that severe disease can occur in about 13.8% of cases and 6.1% are critical.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> When cases are fulminant, patients may develop sepsis, acute respiratory failure syndrome (ARDS) or multiple organ failure, which are not exclusive to coronaviruses. Cytokine release syndrome (CRS) refers to an uncontrolled and exaggerated release of pro-inflammatory mediators into the activated immune system.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> This disturbance may be present in various clinical entities, including the rheumatology setting, Still's disease, systemic juvenile idiopathic arthritis, systemic lupus erythematosus and catastrophic antiphospholipid syndrome (APS). CRS is involved in the immunopathogenesis of many pathological processes, such as ARDS, sepsis, Macrophage activation syndrome (MAS), etc., several of which are described in severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and also in the new COVID-19 infection.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> While treatment directed against the virus is desired, treatment of the systemic response is possibly the most important aspect of patient care and should be viewed aggressively. Finally, patients with COVID-19 who develop a severe condition may have a procoagulant pattern.<a class="elsevierStyleCrossRef" href="#bib0020">4</a> Therefore, this review synthesizes the evidence related to therapies with an anti-inflammatory role that can play a relevant role in the management of patients with severe COVID-19, briefly mentioning the role of antithrombotic therapy in the treatment of complicated patients.GlucocorticoidsGlucocorticoids (GC) are some of the most widely used anti-inflammatory agents; they are commonly prescribed in the treatment of patients with COVID-19 (72% in the ICU).<a class="elsevierStyleCrossRef" href="#bib0025">5</a> However, as mentioned in the Chinese COVID-19 guidelines,<a class="elsevierStyleCrossRef" href="#bib0030">6</a> physicians must be careful in the use of GCs because of their uncertain benefits in the context of viral respiratory infection. Several studies have reported inferior results in SARS patients treated with GC,<a class="elsevierStyleCrossRef" href="#bib0035">7</a> due to delayed purging of the virus. Other concerns with GCs are short-term and long-term adverse effects.Antimalarials (chloroquine and hydroxychloroquine)Recent publications have drawn attention to the possible beneficial effect of hydroxychloroquine (HCQ) and chloroquine (CLQ) in the treatment of patients infected with the new SARS-CoV-2 coronavirus. It has been observed that the growth of several different viruses (including SARS coronavirus) can be inhibited in cell cultures by both CLQ and HCQ. In addition, these drugs are weak bases that can affect acidic vesicles and inhibit several enzymes. This characteristic enables inhibiting of viral entry into cells when endocytosis is pH dependent. They also inhibit the enzyme glycosyltransferase (inhibition of virus glycosylation), post-transcriptional viral modifications and replication of some viral families. As it is known that COVID-19 infection can on occasion lead to severe pictures with SARS, which can be due in part to the increase of proinflammatory cytokines such as interleukin 6 (IL-6) and tumour necrosis factor-alpha (TNF-α). CLQ is highly effective in combination with remdesivir in controlling SARS-CoV-2<a class="elsevierStyleCrossRef" href="#bib0040">8</a> in vitro. There is now already some evidence in humans. In an open observational study conducted in France, they evaluated the role of HCQ in combination with azithromycin on respiratory viral load in 20 patients with COVID-19 compared with 16 controls.<a class="elsevierStyleCrossRef" href="#bib0045">9</a> A significant reduction in viral load was shown (70% at day 7) compared to the controls. When azithromycin was added, more efficient elimination of the virus was found (100% reduction). Gao et al. described results in 100 patients in China where they demonstrated the superiority of CLQ over the control treatment in inhibiting exacerbation of pneumonia, improving lung imaging findings, promoting negative virus conversion, and shortening the course of the disease.<a class="elsevierStyleCrossRef" href="#bib0050">10</a> However, the details of this study are not known in depth. A recent study reported the results of a retrospective analysis of 368 hospitalized patients with confirmed SARS-CoV-2 infection (U.S. Veterans Health Administration) of evaluation of exposure to HCQ alone or in combination with azithromycin.<a class="elsevierStyleCrossRef" href="#bib0055">11</a> The mortality rates in the HCQ alone, combined HQC, and no HQC groups were 27.8%, 22.1%, and 11.4%, respectively. Ventilation rates in the HCQ, combined HCQ and no HCQ groups were 13.3%, 6.9% and 14.1%, respectively. In this study, no evidence was found that the use of HCQ alone or combined reduces the risk of mechanical ventilation in hospitalized patients with COVID-19 and that patients receiving HCQ alone had the highest mortality rate. These findings highlight the importance of waiting for the results of the prospective randomized studies that are underway before widely adopting these drugs. There are currently about 14 clinical trials registered to prove the benefit of antimalarials. Although antimalarials are relatively safe drugs, it should be remembered that their most frequent effects are gastrointestinal, pruritus, and dermal changes in 10% of patients. The most serious effects are of low incidence, such as cardiomyotoxicity, neuromyopathy, and irreversible retinopathy (large doses and long term).Tocilizumab, inleukin-6 inhibitorThere has recently been much interest in the possibility of using tocilizumab, a humanized antibody targeting the IL-6 receptor, on the grounds of preventing or treating the cytokine storm that has been observed in patients that progress to cardiovascular collapse, multiorgan dysfunction, and death.<a class="elsevierStyleCrossRef" href="#bib0060">12</a> Inflammatory cytokines and chemokines, including IL-6, IL-1β, induced protein 10, and monocyte chemotactic protein-1, have been found to be significantly elevated in Covid-19 patients, and are more often elevated in severe patients than in non-severe patients.<a class="elsevierStyleCrossRef" href="#bib0065">13</a> In patients with COVID-19, with elevated inflammatory cytokines, post mortem pathology revealed tissue necrosis and infiltrations of macrophages and monocytes in the lung, heart and gastrointestinal mucosa,<a class="elsevierStyleCrossRef" href="#bib0070">14</a> which suggests an uncontrolled immune response.Studies have shown that ARDS occurs in some SARS patients despite a reduced viral load, suggesting that an exuberant immune response rather than viral virulence is possibly responsible for the pathology at tissue level. Therefore, antiviral therapy alone may not be sufficient.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> As previously mentioned, IL-6 is one of the cytokines that plays a role in the pathogenesis in patients with severe COVID-19; it has also been suggested as a biomarker of severe disease,<a class="elsevierStyleCrossRef" href="#bib0080">16</a> and therefore blockade may be a promising strategy for COVID-19-induced CRS.IL-6 is essential for the generation of T-helper 17 (Th17) lymphocytes in the interaction between T-lymphocytes and dendritic cells.<a class="elsevierStyleCrossRef" href="#bib0085">17</a> Therefore elevated IL-6 may explain the excessive Th17 activation observed in patients with COVID-19, as reported by Xu et al.<a class="elsevierStyleCrossRef" href="#bib0070">14</a> Although no data are available on IL-6 blockade in CRS induced by viral infection, animal studies of SARS-CoV have shown that they inhibit nuclear factor kappa-B, an essential transcription factor of IL-6, increasing animal survival with reduced levels of IL-6.<a class="elsevierStyleCrossRef" href="#bib0090">18</a> Tocilizumab, which blocks IL-6, binds to the IL-6 receptor in both soluble and membrane-bound forms to inhibit IL-6-mediated signals. This drug has been approved by the Food and Drug Administration for the treatment of CRS associated with CAR T-cell therapy.Data on the use of this molecule in the treatment of SARS-CoV-2 infection are still preliminary but promising results have prompted the Chinese Health Commission to update its national guidelines, which include tocilizumab for the treatment of severe COVID-19.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> The Italian guidelines also support the use of tocilizumab (at a dose of 8 mg/kg, with a second dose 12 h after the first and a possible third after 24-36 h, depending on the clinical response), in the event of rapid clinical or radiological worsening, after excluding contraindications to its use (levels of transaminases >5 times the upper limit of normal, neutrophil count <50,000 cells/μl, presence of documented sepsis complicated by bacteria, diverticulitis/intestinal perforation, skin infection).<a class="elsevierStyleCrossRef" href="#bib0100">20</a>There are case reports of improvement in patients with severe COVID-19 after the administration of tocilizumab.<a class="elsevierStyleCrossRefs" href="#bib0105">21,22</a>Interleukin 1b inhibitors and protein kinase inhibitors JAK1/2 (roxulitinib)Several laboratory markers related to MAS/ haemaphagocytic lymphohistiocytosis (HLH) are elevated in severe COVID-19.<a class="elsevierStyleCrossRef" href="#bib0115">23</a> Therefore, treatments aimed at controlling MAS/HLH have been suggested for the management of severe COVID-19. The recombinant human IL-1 receptor antagonist, anakinra, has been used for the treatment of MAS/HLH associated with autoimmune rheumatic diseases.<a class="elsevierStyleCrossRef" href="#bib0120">24</a> Data from a reanalysis of a phase iii controlled trial found that anakinra was associated with significant improvement in the survival of patients with sepsis with concurrent MAS/HLH.<a class="elsevierStyleCrossRef" href="#bib0125">25</a>Small molecule inhibiting Janus kinases, such as the JAK1/2 inhibitor ruxolitinib,<a class="elsevierStyleCrossRef" href="#bib0130">26</a> are capable of blocking signals from IL-6, interferon γ (IFN-γ) and other cytokines involved in MAS/HLH. Therefore, this drug could have potential in the treatment of serious complications in patients with COVID-19. More recently, the use of anti-IFN-γ antibodies has been contemplated in the management of this serious complication.<a class="elsevierStyleCrossRef" href="#bib0135">27</a>Intravenous immunoglobulin and plasma from recovered patients (“convalescent plasma”)Individuals with a weakened immune system appear to be at greater risk of developing complications associated with COVID-19. Immunotherapy using IgG in combination with antiviral drugs could be used to treat or prevent SARS-CoV-2 infection and strengthen our immune system against this virus.<a class="elsevierStyleCrossRefs" href="#bib0140">28,29</a> They have also have been administered as anti-infective agents against viruses, bacteria and fungi in experimental models and in humans.<a class="elsevierStyleCrossRef" href="#bib0150">30</a> IVIGs can modulate the immune response by several mechanisms, including blocking various pro-inflammatory cytokines, Fc receptors, and leukocyte adhesion molecules, suppressing Th1 and Th17 cell subtypes, and neutralizing pathogenic autoantibodies.<a class="elsevierStyleCrossRef" href="#bib0155">31</a> IVIGs can also expand regulatory T lymphocytes.<a class="elsevierStyleCrossRef" href="#bib0160">32</a> However, IVIGs have adverse reactions. During the SARS outbreak in 2003, IVIG was used extensively in Singapore. However, some critically ill patients developed venous thromboembolism (VTE) including pulmonary embolism despite the use of prophylactic low molecular weight heparin.<a class="elsevierStyleCrossRef" href="#bib0165">33</a> This is due to the increased viscosity in hypercoagulable states of SARS patients.Convalescent plasma samples have been used to treat SARS in Hong Kong and China and may be valuable because, unlike standard IVIG preparations, they have high levels of anti-SARS-CoV antibodies.<a class="elsevierStyleCrossRef" href="#bib0170">34</a> Pyrc et al. showed that human serum from adult humans inhibited infection by HCov-NL63.<a class="elsevierStyleCrossRef" href="#bib0140">28</a> Furthermore, they described that IVIGs can also neutralize HCoV-NL63. Boukhvalova et al.<a class="elsevierStyleCrossRef" href="#bib0175">35</a> demonstrated that, in contrast, the commercially available therapeutic polyclonal IgG products, IVIG obtained from donors with antibodies at high titres against respiratory syncytial virus (RSV), have great potential in improving RSV outcomes in immunocompromised subjects, not only controlling viral replication, but also reducing damage to the lung parenchyma and the epithelial lining of the respiratory tract. The use of convalescent plasma or serum was also suggested by the WHO under the Blood Regulators Network should vaccines and antiviral drugs not be available in an emerging virus. In the current pandemic, there are reports that convalescent plasma has been used in China to treat patients with COVID-19.<a class="elsevierStyleCrossRef" href="#bib0180">36</a> In a pilot study of 10 patients with severe COVID-19, investigators collected convalescent plasma with neutralizing antibody titres at a dilution of 1:640 or more.<a class="elsevierStyleCrossRef" href="#bib0185">37</a> The convalescent plasma transfusion resulted in no serious adverse events in the receivers. All 10 patients had improvement of symptoms (e.g., fever, cough, shortness of breath, and precordial pain) within 1-3 days of the transfusion; they also showed radiological improvement in lung lesions. Similarly, an undetectable viral load was found in most of them.IgG immunotherapy could be used to neutralize the virus causing COVID-19. The efficiency of IgG could be improved if these immune IgG antibodies were collected from patients who had recovered from COVID-19 in the same city, or surrounding areas, as donor subjects who have dealt with the virus.Plasma interchangeTherapeutic apheresis encompasses a large number of techniques the main basis of which is to process a patient's blood through an extracorporeal device with the aim of eliminating antibodies and preformed immunocomplexes to prevent tissue damage, eliminating inflammation mediators as a complement and cytokines that could contribute to damage, and providing deficiency factors.<a class="elsevierStyleCrossRef" href="#bib0190">38</a> Among the different types of apheresis, some of the most used are therapeutic plasma exchange (PE) and immunoadsorption. Therapeutic PE is a technique for purifying extracorporeal blood, through which plasma is removed. A variable volume of plasma is removed from the patient and replaced with replacement solutions that maintain volume and oncotic pressure. The term "plasmapheresis" should be reserved for situations in which only plasma removal without replenishment is performed, such as plasma donation by apheresis for transfusion or subsequent industrial plasma fractionation. This procedure extracts less plasma (around 600 ml), without replenishment solution, in less time and with simpler separation techniques than those used in PE. The host response to infection has been described and involves a complex interaction of cytokine storm, inflammation, endothelial dysfunction, and pathological coagulation. Plasma exchange is a pathway that offers benefit at multiple levels by removing inflammatory cytokines, stabilizing endothelial membranes, and restarting the hypercoagulable state.Busund et al.<a class="elsevierStyleCrossRef" href="#bib0195">39</a> showed a trend towards improving mortality with therapeutic PE as an adjuvant treatment in adults with sepsis and multiple organ failure in a controlled clinical trial, while a meta-analysis by Rimmer also showed benefit in adult patient mortality.<a class="elsevierStyleCrossRef" href="#bib0200">40</a> Addressing this information, Patel et al.<a class="elsevierStyleCrossRef" href="#bib0205">41</a> used therapeutic PE during the 2009 A (H1N1) influenza epidemic in 3 paediatric patients with a fulminant condition similar to the current pandemic. All 3 patients developed ARDS with haemodynamic compromise that continued to deteriorate despite rescue treatment for ARDS including inhaled nitric oxide and extracorporeal venous membrane oxygenation. All 3 patients made a full recovery from their disease after receiving rescue PE. Recently, 3 patients were described with COVID-19 in Wuhan, China,<a class="elsevierStyleCrossRef" href="#bib0210">42</a> characterized by deep inflammation and treated with blood purification therapies, including PE and adsorption. A potent effect on cytokine storm management and pathogenic antibodies was shown. Of these 3 patients, 2 maintained a stable state and could be discharged from the Intensive Care Unit, while one developed disseminated intravascular coagulation (DIC) and died.Antithrombotic therapySevere COVID-19 can often present a marked elevation of D-dimer, thrombocytopenia and coagulation disturbances that are considered to be regulated by various inflammatory cytokines<a class="elsevierStyleCrossRefs" href="#bib0215">43,44</a> and that correlate with mortality. Another biomarker that has been found to be elevated in patients with severe COVID-19 is ferritin,<a class="elsevierStyleCrossRef" href="#bib0060">12</a> which is also impaired in other severe conditions, including APS in its most severe form, catastrophic APS.<a class="elsevierStyleCrossRef" href="#bib0225">45</a> Recently, a group from China described 3 cases with COVID-19 and antiphospholipid antibodies.<a class="elsevierStyleCrossRef" href="#bib0230">46</a> Recent statements by the International Society on Thrombosis and Haemostasis (ISTH) and the American Society of Hematology (ASH) suggest that all patients hospitalized with COVID-19 should receive thromboprophylaxis or full-dose therapeutic anticoagulation. The efficacy of anticoagulation therapy in patients with COVID-19 was recently evaluated retrospectively. Lower mortality at 28 days was found in patients who used heparin (40%) compared to those who did not (64.2%), mainly in those with sepsis-induced coagulopathy or with a markedly elevated D-dimer.<a class="elsevierStyleCrossRef" href="#bib0235">47</a><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> summarizes the antithrombotic recommendations for patients with COVID-19.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>ConclusionsCOVID-19 is a viral infection with potentially serious complications that can increase the risk of death in infected patients. Several of these disturbances are secondary to an uncontrolled immune response where a cytokine storm plays a similarly important role in preventing the thrombotic complications to which these patients are exposed. Although antiviral treatment and respiratory support therapies are essential in the treatment of severe cases, it is necessary to assess the risk-benefit of therapies aimed at controlling the immune response to decrease the mortality rate.FundingThis research study has received no specific support from public sector agencies, the commercial sector, or non-profit entities.Conflict of interestsThe authors have no conflict of interests to declare" "textoCompletoSecciones" => array:1 [ "secciones" => array:16 [ 0 => array:3 [ "identificador" => "xres1584153" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1425603" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1584154" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1425602" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Glucocorticoids" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Antimalarials (chloroquine and hydroxychloroquine)" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Tocilizumab, inleukin-6 inhibitor" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Interleukin 1b inhibitors and protein kinase inhibitors JAK1/2 (roxulitinib)" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Intravenous immunoglobulin and plasma from recovered patients (“convalescent plasma”)" ] 10 => array:2 [ "identificador" => "sec0035" "titulo" => "Plasma interchange" ] 11 => array:2 [ "identificador" => "sec0040" "titulo" => "Antithrombotic therapy" ] 12 => array:2 [ "identificador" => "sec0045" "titulo" => "Conclusions" ] 13 => array:2 [ "identificador" => "sec0055" "titulo" => "Funding" ] 14 => array:2 [ "identificador" => "sec0050" "titulo" => "Conflict of interests" ] 15 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-04-28" "fechaAceptado" => "2020-05-08" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1425603" "palabras" => array:3 [ 0 => "COVID-19" 1 => "Coronavirus" 2 => "Cytokine release syndrome" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1425602" "palabras" => array:3 [ 0 => "COVID-19" 1 => "Coronavirus" 2 => "Síndrome de liberación de citocinas" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "The novel SARS-CoV-2 human coronavirus in Wuhan, China, has triggered a worldwide respiratory disease outbreak (COVID-19). Acute respiratory distress syndrome (ARDS), multiorgan dysfunction and thrombotic events are among the leading causes of death in critically ill patients with COVID-19. The elevated inflammatory cytokines suggest that a “cytokine storm”, also known as cytokine release syndrome (CRS), may play a major role in the pathology of COVID-19. In addition to anti-viral therapy and supportive treatment in critically ill patients, unique medications for this condition are also under investigation. Here we reviewed therapeutic options, including the antibody therapy that might be an immediate strategy for SARS-CoV-2 therapy." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "El inicio del nuevo coronavirus humano del síndrome respiratorio agudo grave (SARS-Cov-2) en Wuhan, China, ha desencadenado un brote respiratorio mundial (COVID-19). El síndrome de insuficiencia respiratoria agua (SIRA), el fallo multiorgánico y eventos trombóticos están entre las causas que llevan a la muerte en pacientes críticamente enfermos con COVID-19. Las citocinas inflamatorias elevadas sugieren que una “tormenta de citocinas”, también conocida como síndrome de liberación de citocinas (SLC), puede jugar un papel principal en la patología de COVID-19. Adicionalmente al tratamiento anti-viral y la terapia de apoyo respiratorio en pacientes críticamente enfermos, están en investigación medicamentos únicos para esta condición. En esta revisión sintetizamos la evidencia más actual de opciones terapéuticas, incluyendo anticuerpos anti-citocinas como una estrategia intermedia para la terapia de SARS-Cov-2." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Mendoza-Pinto C, García-Carrasco M, Munguía Realpozo P, Méndez-Martínez S. Opciones terapéuticas en el manejo de la COVID-19 grave: una perspectiva de Reumatología. Reumatol Clin. 2021;17:431–436." ] ] "multimedia" => array:1 [ 0 => array:9 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Source: Bikdeli et al.<a class="elsevierStyleCrossRef" href="#bib0240">48</a>" "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "DOA: direct oral anticoagulants; DIC: disseminated intravascular coagulation; LMWH: low molecular weight heparin; INR: international normalized ratio; VTE: venous thromboembolism." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Patients with mild COVID-19 (outpatient) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">For outpatients with COVID-19, increased mobility should be encouraged. Although indiscriminate use of pharmacological VTE prophylaxis should not be pursued, assessment for the risk of VTE and of bleeding is reasonable. Pharmacologic prophylaxis could be considered after risk assessment on an individual case basis for patients who have elevated risk VTE, without high bleeding risk \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">There is no known risk of developing severe COVID-19 due to taking antithrombotic agents (i.e., antiplatelet agents or anticoagulants). If patients were taking antithrombotic agents for prior known thrombotic disease, they should continue their antithrombotic therapy as recommended \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">For patients on vitamin K antagonists who do not have recent stable INRs, and are unable to undergo INR testing, it is reasonable to transition the treatment DOACs if there are no contraindications and no problems with drug availability. If DOACs are not approved or available, LMWH (enoxaparin 40 mg/day) can be considered \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Patients with moderate or severe COVID-19 without DIC hospitalised \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Hospitalized patients with COVID-19 should undergo risk stratification for VTE prophylaxis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">For hospitalized patients with COVID-19 and not in DIC, prophylactic doses of anticoagulation should be administered to prevent VTE (enoxaparin 40 mg/day or dalteparin 5000 U daily; subcutaneous heparin 5000 U twice daily may be considered for patients with kidney failure [e.g., creatinine clearance <30 ml/min]). If pharmacological prophylaxis is contraindicated, it is reasonable to consider intermittent pneumatic compression \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">For hospitalised patients with COVID-19 and not in DIC, there are insufficient data to consider routine therapeutic or parenteral therapeutic doses with LMWH (e.g., enoxaparin 1 mg/kg/day, or enoxaparin 40 mg twice a day) or unfractionated heparin (with an activated PTT target of 50−70) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Routine screening for VTE is not recommended (e.g., bilateral lower extremity ultrasound) for hospitalized patients with COVID-19 with elevated D-dimer \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Patients with moderate to severe COVID-19 hospitalised and suspected DIC \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">For patients with moderate to severe COVID-19 and in DIC but without overt bleeding, prophylactic anticoagulation should be administered \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">For hospitalized patients with COVID-19 with suspected or confirmed DIC with no overt bleeding, there are insufficient data to consider routine therapeutic-dose parenteral anticoagulation at therapeutic doses with LMWH or unfractionated heparin \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">For patients with moderate or severe COVID-19 on chronic therapeutic anticoagulation, who develop suspected or confirmed DIC without overt bleeding, it is reasonable to consider the indication for anticoagulation and to weigh with risk of bleeding when making clinical decisions regarding dose adjustments or discontinuation. It is recommended to reduce the intensity of anticoagulation in this clinical circumstance, unless the risk of thrombosis is considered to be exceedingly high \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">For patients with moderate or severe COVID-19 and an indication for dual antiplatelet therapy (e.g., percutaneous coronary intervention in the past 3 months or recent myocardial infarction) and with suspected or confirmed DIC with no overt bleeding, in the absence of evidence, decisions for antiplatelet therapy need to be individualized. In general, it is reasonable to continue dual antiplatelet therapy (aspirin plus a P2Y receptor inhibitor such as clopidogrel) if platelet count is >50,000, reduce to a single therapy if platelet count is 25,000 and 50,000, and discontinue if platelet count is <25,000. However, these guidelines may be revised depending on the individualized relative risk of thrombotic complications vs. bleeding \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">For patients who were admitted and are now being discharged for COVID-19 and now discharged, routine screening for VTE risk is reasonable for consideration of pharmaceutical prophylaxis for up to 45 days post-discharge. Pharmacological prophylaxis should be considered if there is elevated risk for thrombotic events, without bleeding risk. Ambulation and physical activity should be encouraged \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Patients without COVID-19 who have previously known thrombotic disease \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">There is no known risk of developing COVID-19 due to the administration of antithrombotic agents. Patients should continue treatment with antithrombotic agent as recommended \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">To minimize risks associated with health care worker and patient in-person interactions, follow-up with e.visits and telemedicine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Patients without COVID-19 who develop new thrombotic disease \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">To minimize the risks associated with health care worker and patient in-person interactions, in-home treatment or early discharge should be prioritized with electronic or telemedicine follow-up \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Patients without COVID-19 but with comorbid conditions (e.g., prior history of VTE, active cancer, major lung disease) who are homebound \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Recommendations include increased mobility, and risk assessment for the risk of VTE and risk of bleeding is reasonable \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Administration of pharmacological prophylaxis could be considered after risk assessment on an individual case basis based on their risk for thrombosis and bleeding risk \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2713338.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Summary of the consensus on recommendations for antithrombotic therapy during the COVID-19 pandemic." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:48 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Aylward, Bruce (WHO); Liang W (PRC). Report of the WHO-China JointMission on Coronavirus Disease 2019 (COVID-19). WHO-China Jt Mis-sion Coronavirus Dis 2019 [Internet]. 2020;2019(February):16–24. Available from: <a target="_blank" href="https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf">https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf</a>." ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Current concepts in the diagnosis and management of cytokine release syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.W. Lee" 1 => "R. Gardner" 2 => "D.L. Porter" 3 => "C.U. Louis" 4 => "N. Ahmed" 5 => "M. Jensen" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Blood." "fecha" => "2014" "volumen" => "124" "paginaInicial" => "188" "paginaFinal" => "195" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China [published online ahead of print, 2020 Mar 13]" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Wu" 1 => "X. Chen" 2 => "Y. Cai" 3 => "J. Xia" 4 => "X. Zhou" 5 => "S. Xu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/jamainternmed.2020.0994.4" "Revista" => array:3 [ "tituloSerie" => "JAMA Intern Med" "fecha" => "2020" "paginaInicial" => "e200994" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Incidence of thrombotic complications in critically ill ICU patients with COVID-19" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F.A. Klok" 1 => "M. Kruip" 2 => "N.J.M. van der Meer" 3 => "M.S. Arbous" 4 => "D.A.M.P.J. Gommers" 5 => "K.M. Kant" ] ] ] ] ] "host" => array:2 [ 0 => array:1 [ "Revista" => array:2 [ "tituloSerie" => "Thromb Res [Internet]" "fecha" => "2020" ] ] 1 => array:1 [ "WWW" => array:1 [ "link" => "https://linkinghub.elsevier.com/retrieve/pii/S0049384820301201" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Wang" 1 => "B. Hu" 2 => "C. Hu" 3 => "F. Zhu" 4 => "X. Liu" 5 => "J. Zhang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/jama.2020.1585" "Revista" => array:6 [ "tituloSerie" => "JAMA" "fecha" => "2020" "volumen" => "323" "paginaInicial" => "1061" "paginaFinal" => "1069" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32031570" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Y.-H. Jin" 1 => "L. Cai" 2 => "Z.-S. Cheng" 3 => "Z.-S. Cheng" 4 => "T. Deng" 5 => "Y.-P. Fan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s40779-020-0233-6" "Revista" => array:5 [ "tituloSerie" => "Mil Med Res" "fecha" => "2020" "volumen" => "7" "paginaInicial" => "4" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32029004" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "C.D. Russell" 1 => "J.E. Millar" 2 => "J.K. Baillie" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(20)30317-2" "Revista" => array:5 [ "tituloSerie" => "Lancet [Internet]" "fecha" => "2020" "volumen" => "395" "paginaInicial" => "473" "paginaFinal" => "475" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Wang" 1 => "R. Cao" 2 => "L. Zhang" 3 => "X. Yang" 4 => "J. Liu" 5 => "M. Xu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/s41422-020-0282-0" "Revista" => array:6 [ "tituloSerie" => "Cell research" "fecha" => "2020" "volumen" => "30" "paginaInicial" => "269" "paginaFinal" => "271" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32020029" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Gautret" 1 => "J.-C. Lagier" 2 => "P. Parola" 3 => "V.T. Hoang" 4 => "L. Meddeb" 5 => "M. Mailhe" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:2 [ "tituloSerie" => "Int J Antimicrob Agents" "fecha" => "2020" ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J. Gao" 1 => "Z. Tian" 2 => "X. Yang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.5582/bst.2020.01047" "Revista" => array:6 [ "tituloSerie" => "Biosci Trends" "fecha" => "2020" "volumen" => "14" "paginaInicial" => "72" "paginaFinal" => "73" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32074550" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Outcomes of hydroxychloroquine usage  in United States veterans hospitalized with Covid-19" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Magagnoli" 1 => "S. Narendran" 2 => "F. Pereira" 3 => "T. Cummings" 4 => "J.W. Hardin" 5 => "S.S. Sutton" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:2 [ "tituloSerie" => "medRxiv [Internet]" "fecha" => "2020" ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Chen" 1 => "M. Zhou" 2 => "X. Dong" 3 => "J. Qu" 4 => "F. Gong" 5 => "Y. Han" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(20)30211-7" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2020" "volumen" => "395" "paginaInicial" => "507" "paginaFinal" => "513" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32007143" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Characteristics of lymphocyte subsets and cytokines in peripheral blood of 123 hospitalized patients with 2019 novel coronavirus pneumonia (NCP)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Wan" 1 => "Q. Yi" 2 => "S. Fan" 3 => "J. Lv" 4 => "X. Zhang" 5 => "L. Guo" ] ] ] ] ] "host" => array:2 [ 0 => array:1 [ "Revista" => array:2 [ "tituloSerie" => "medRxiv [Internet]" "fecha" => "2020" ] ] 1 => array:1 [ "WWW" => array:1 [ "link" => "http://medrxiv.org/content/early/2020/02/12/2020.02.10.20021832.abstract" ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pathological findings of COVID-19 associated with acute respiratory distress syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Z. Xu" 1 => "L. Shi" 2 => "Y. Wang" 3 => "J. Zhang" 4 => "L. Huang" 5 => "C. Zhang" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Lancet Resp Med" "fecha" => "2020" "volumen" => "8" "paginaInicial" => "420" "paginaFinal" => "422" ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.S.M. Peiris" 1 => "C.M. Chu" 2 => "V.C.C. Cheng" 3 => "K.S. Chan" 4 => "I.F.N. Hung" 5 => "L.L.M. Poon" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/s0140-6736(03)13412-5" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2003" "volumen" => "361" "paginaInicial" => "1767" "paginaFinal" => "1772" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12781535" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID-19" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Y. Gao" 1 => "T. Li" 2 => "M. Han" 3 => "X. Li" 4 => "D. Wu" 5 => "Y. Xu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/jmv.25770" "Revista" => array:2 [ "tituloSerie" => "J Med Virol." "fecha" => "2020" ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Immunotherapeutic implications of IL-6 blockade for cytokine storm" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "T. Tanaka" 1 => "M. Narazaki" 2 => "T. Kishimoto" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2217/imt-2016-0020" "Revista" => array:6 [ "tituloSerie" => "Immunotherapy" "fecha" => "2016" "volumen" => "8" "paginaInicial" => "959" "paginaFinal" => "970" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27381687" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0090" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inhibition of NF-kappaB-mediated inflammation in severe acute respiratory syndrome coronavirus-infected mice increases survival" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.L. DeDiego" 1 => "J.L. Nieto-Torres" 2 => "J.A. Regla-Nava" 3 => "J.M. Jimenez-Guardeno" 4 => "R. Fernandez-Delgado" 5 => "C. Fett" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/JVI.02576-13" "Revista" => array:6 [ "tituloSerie" => "J Virol" "fecha" => "2014" "volumen" => "88" "paginaInicial" => "913" "paginaFinal" => "924" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24198408" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0095" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnosis and treatment protocol for novel coronavirus pneumonia.Trial Version 7 (Released by National Health Commission & National Administra-tion of Traditional Chinese Medicine on March 3, 2020). Diagnosis and TreatmentProtocol for Novel Coronavirus Pneumonia (Trial Version 7)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "National Health Commission & State Administration of Traditional Chinese Medicine" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/CM9.0000000000000819" "Revista" => array:6 [ "tituloSerie" => "Chin Med J (Engl)" "fecha" => "2020" "volumen" => "133" "numero" => "9" "paginaInicial" => "1087" "paginaFinal" => "1095" ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0100" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "SIMIT Società Italiana di Malattie Infettive e Tropicali. Linee guida sulla gestione terapeutica e di supporto per pazienti con infezione da coronavirus COVID-19. Edizione 2.0, 12 marzo 2020. [Internet]. Available from: <a target="_blank" href="http://www.simit.org/medias/1569-covid19-vademecum-13-03-202.pdf">http://www.simit.org/medias/1569-covid19-vademecum-13-03-202.pdf</a>." ] ] ] 20 => array:3 [ "identificador" => "bib0105" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tocilizumab, an anti-IL6 receptor antibody, to treat Covid-19-related respiratory failure: a case report" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.-M. Michot" 1 => "L. Albiges" 2 => "N. Chaput" 3 => "V. Saada" 4 => "F. Pommeret" 5 => "F. Griscelli" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.annonc.2020.03.300" "Revista" => array:3 [ "tituloSerie" => "Ann Oncol" "fecha" => "2020" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33736838" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0110" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "B. Liu" 1 => "M. Li" 2 => "Z. Zhou" 3 => "X. Guan" 4 => "Y. Xiang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaut.2020.102452" "Revista" => array:2 [ "tituloSerie" => "J Autoimmun" "fecha" => "2020" ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0115" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in china: summary of a report of 72314 cases from the Chinese center for disease control and prevention" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Z. Wu" 1 => "J.M. McGoogan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/jama.2020.2648" "Revista" => array:6 [ "tituloSerie" => "JAMA" "fecha" => "2020" "volumen" => "323" "paginaInicial" => "1239" "paginaFinal" => "1242" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32091533" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Benefit of anakinra in treating pediatric secondary hemophagocytic lymphohistiocytosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E.M. Eloseily" 1 => "P. Weiser" 2 => "C.B. Crayne" 3 => "H. Haines" 4 => "M.L. Mannion" 5 => "M.L. Stoll" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/art.41103" "Revista" => array:6 [ "tituloSerie" => "Arthritis Rheumatol" "fecha" => "2020" "volumen" => "72" "paginaInicial" => "326" "paginaFinal" => "334" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31513353" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0125" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Interleukin-1 receptor blockade is associated with reduced mortality in sepsis patients with features of macrophage activation syndrome: reanalysis of a prior phase III trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B. Shakoory" 1 => "J.A. Carcillo" 2 => "W.W. Chatham" 3 => "R.L. Amdur" 4 => "H. Zhao" 5 => "C.A. Dinarello" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/CCM.0000000000001402" "Revista" => array:6 [ "tituloSerie" => "Crit Care Med" "fecha" => "2016" "volumen" => "44" "paginaInicial" => "275" "paginaFinal" => "281" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26584195" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0130" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Therapeutic effect of JAK1/2 blockade on the manifestations of hemophagocytic lymphohistiocytosis in mice" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "S. Maschalidi" 1 => "F.E. Sepulveda" 2 => "A. Garrigue" 3 => "A. Fischer" 4 => "G. de Saint Basile" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2016-02-700013" "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2016" "volumen" => "128" "paginaInicial" => "60" "paginaFinal" => "71" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27222478" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0135" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "An animal model of hemophagocytic lymphohistiocytosis (HLH): CD8+T cells and interferon gamma are essential for the disorder" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M.B. Jordan" 1 => "D. Hildeman" 2 => "J. Kappler" 3 => "P. Marrack" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2003-10-3413" "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2004" "volumen" => "104" "paginaInicial" => "735" "paginaFinal" => "743" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15069016" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0140" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inhibition of human coronavirus NL63 infection at early stages of the replication cycle" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. Pyrc" 1 => "B.J. Bosch" 2 => "B. Berkhout" 3 => "M.F. Jebbink" 4 => "R. Dijkman" 5 => "P. Rottier" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1128/AAC.01598-05" "Revista" => array:6 [ "tituloSerie" => "Antimicrob Agents Chemother" "fecha" => "2006" "volumen" => "50" "paginaInicial" => "2000" "paginaFinal" => "2008" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16723558" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0145" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Coronavirus associated fulminant myocarditis successfully treated with intravenous immunoglobulin and extracorporeal membrane oxygenation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "S. Rao" 1 => "W. Sasser" 2 => "F. Diaz" 3 => "N. Sharma" 4 => "J. Alten" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1378/chest.1992018" "Revista" => array:4 [ "tituloSerie" => "Chest [Internet]" "fecha" => "2014" "volumen" => "146" "paginaInicial" => "336A" ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0150" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "IVIG-mediated protection against necrotizing pneumonia caused by MRSA" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B.A. Diep" 1 => "V.T.M. Le" 2 => "C. Badiou" 3 => "H.N. Le" 4 => "M.G. Pinheiro" 5 => "A.H. Duong" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1126/scitranslmed.aaf0746" "Revista" => array:4 [ "tituloSerie" => "Sci Transl Med" "fecha" => "2016" "volumen" => "8" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26843188" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0155" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Intravenous immunoglobulin exerts reciprocal regulation of Th1/Th17 cells and regulatory T cells in Guillain-Barre syndrome patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.S. Maddur" 1 => "M. Rabin" 2 => "P. Hegde" 3 => "F. Bolgert" 4 => "M. Guy" 5 => "J.-M. Vallat" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s12026-014-8580-6" "Revista" => array:6 [ "tituloSerie" => "Immunol Res" "fecha" => "2014" "volumen" => "60" "paginaInicial" => "320" "paginaFinal" => "329" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25391612" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0160" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Intravenous immunoglobulin expands regulatory T cells via induction of cyclooxygenase-2-dependent prostaglandin E2 in human dendritic cells" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Trinath" 1 => "P. Hegde" 2 => "M. Sharma" 3 => "M.S. Maddur" 4 => "M. Rabin" 5 => "J.-M. Vallat" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1182/blood-2012-11-468264" "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2013" "volumen" => "122" "paginaInicial" => "1419" "paginaFinal" => "1427" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23847198" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0165" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Acute respiratory distress syndrome in critically ill patients with severe acute respiratory syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T.W.K. Lew" 1 => "T.-K. Kwek" 2 => "D. Tai" 3 => "A. Earnest" 4 => "S. Loo" 5 => "K. Singh" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/jama.290.3.374" "Revista" => array:6 [ "tituloSerie" => "JAMA" "fecha" => "2003" "volumen" => "290" "paginaInicial" => "374" "paginaFinal" => "380" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12865379" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0170" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Deployment of convalescent plasma for the prevention and treatment of COVID-19" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E.M. Bloch" 1 => "S. Shoham" 2 => "A. Casadevall" 3 => "B.S. Sachais" 4 => "B. Shaz" 5 => "J.L. Winters" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1172/JCI138745" "Revista" => array:3 [ "tituloSerie" => "J Clin Invest" "fecha" => "2020" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18431517" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0175" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treatment with novel RSV Ig RI-002 controls viral replication and reduces pulmonary damage in immunocompromised Sigmodon hispidus" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M. Boukhvalova" 1 => "J.C.G. Blanco" 2 => "A.R. Falsey" 3 => "J. Mond" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/bmt.2015.212" "Revista" => array:6 [ "tituloSerie" => "Bone Marrow Transplant" "fecha" => "2016" "volumen" => "51" "paginaInicial" => "119" "paginaFinal" => "126" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26367224" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0180" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Xinhua. China puts 245 COVID-19 patients on convalescent plasma therapy [Internet]. Available from: <a target="_blank" href="http://www.xinhuanet.com/english/2020-02/28/c_138828177.htm">http://www.xinhuanet.com/english/2020-02/28/c_138828177.htm</a>." ] ] ] 36 => array:3 [ "identificador" => "bib0185" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The feasibility of convalescent plasma therapy in severe COVID-19 patients: a pilot study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. Duan" 1 => "B. Liu" 2 => "C. Li" 3 => "H. Zhang" 4 => "T. Yu" 5 => "J. Qu" ] ] ] ] ] "host" => array:2 [ 0 => array:2 [ "doi" => "10.1101/2020.03.16.20036145" "Revista" => array:2 [ "tituloSerie" => "medRxiv [Internet]" "fecha" => "2020" ] ] 1 => array:1 [ "WWW" => array:1 [ "link" => "http://medrxiv.org/content/early/2020/03/23/2020.03.16.20036145.Abstract" ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0190" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Guidelines on the use of therapeutic apheresis in clinical practice-evidence-based approach from the writing committee of the american society for apheresis: the seventh special issue" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Schwartz" 1 => "A. Padmanabhan" 2 => "N. Aqui" 3 => "R.A. Balogun" 4 => "L. Connelly-Smith" 5 => "M. Delaney" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/jca.21470" "Revista" => array:6 [ "tituloSerie" => "J Clin Apher" "fecha" => "2016" "volumen" => "31" "paginaInicial" => "149" "paginaFinal" => "162" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27322218" "web" => "Medline" ] ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0195" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Plasmapheresis in severe sepsis and septic shock: a prospective, randomised, controlled trial" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "R. Busund" 1 => "V. Koukline" 2 => "U. Utrobin" 3 => "E. Nedashkovsky" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00134-002-1410-7" "Revista" => array:6 [ "tituloSerie" => "Intensive Care Med" "fecha" => "2002" "volumen" => "28" "paginaInicial" => "1434" "paginaFinal" => "1439" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12373468" "web" => "Medline" ] ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0200" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The efficacy and safety of plasma exchange in patients with sepsis and septic shock: a systematic review and meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E. Rimmer" 1 => "B.L. Houston" 2 => "A. Kumar" 3 => "A.M. Abou-Setta" 4 => "C. Friesen" 5 => "J.C. Marshall" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s13054-014-0699-2" "Revista" => array:5 [ "tituloSerie" => "Crit Care" "fecha" => "2014" "volumen" => "18" "paginaInicial" => "699" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25527094" "web" => "Medline" ] ] ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0205" "etiqueta" => "41" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Use of therapeutic plasma exchange as a rescue therapy in 2009 pH1N1 influenza A—an associated respiratory failure and hemodynamic shock" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "P. Patel" 1 => "V. Nandwani" 2 => "J. Vanchiere" 3 => "S.A. Conrad" 4 => "L.K. Scott" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/PCC.0b013e3181e2a569" "Revista" => array:6 [ "tituloSerie" => "Pediatr Crit Care Med" "fecha" => "2011" "volumen" => "12" "paginaInicial" => "e87" "paginaFinal" => "e89" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20453703" "web" => "Medline" ] ] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0210" "etiqueta" => "42" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Potential effect of blood purification therapy in reducing cytokine storm as a late complication of critically ill COVID-19" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Ma" 1 => "P. Xia" 2 => "Y. Zhou" 3 => "Z. Liu" 4 => "X. Zhou" 5 => "J. Wang" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Clin Immunol" "fecha" => "2020" "volumen" => "214" ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0215" "etiqueta" => "43" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "S. Yin" 1 => "M. Huang" 2 => "D. Li" 3 => "N. Tang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s11239-020-02105-8. r" "Revista" => array:4 [ "tituloSerie" => "J Thromb Thrombolysis [Internet]" "fecha" => "2020" "paginaInicial" => "3" "paginaFinal" => "6" ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib0220" "etiqueta" => "44" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: a meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "G. Lippi" 1 => "M. Plebani" 2 => "B.M. Henry" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cca.2020.03.022" "Revista" => array:6 [ "tituloSerie" => "Clin Chim Acta" "fecha" => "2020" "volumen" => "506" "paginaInicial" => "145" "paginaFinal" => "148" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32178975" "web" => "Medline" ] ] ] ] ] ] ] ] 44 => array:3 [ "identificador" => "bib0225" "etiqueta" => "45" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ferritin in the antiphospholipid syndrome and its catastrophic variant (cAPS)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Agmon-Levin" 1 => "C. Rosario" 2 => "B.-S.P. Katz" 3 => "G. Zandman-Goddard" 4 => "P. Meroni" 5 => "R. Cervera" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1177/0961203313504633" "Revista" => array:6 [ "tituloSerie" => "Lupus" "fecha" => "2013" "volumen" => "22" "paginaInicial" => "1327" "paginaFinal" => "1335" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24036580" "web" => "Medline" ] ] ] ] ] ] ] ] 45 => array:3 [ "identificador" => "bib0230" "etiqueta" => "46" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Coagulopathy and antiphospholipid antibodies in patients with covid-19" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Y. Zhang" 1 => "M. Xiao" 2 => "S. Zhang" 3 => "P. Xia" 4 => "W. Cao" 5 => "W. Jiang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMc2007575" "Revista" => array:5 [ "tituloSerie" => "N Engl J Med" "fecha" => "2020" "volumen" => "382" "paginaInicial" => "e38" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32268022" "web" => "Medline" ] ] ] ] ] ] ] ] 46 => array:3 [ "identificador" => "bib0235" "etiqueta" => "47" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "N. Tang" 1 => "H. Bai" 2 => "X. Chen" 3 => "J. Gong" 4 => "D. Li" 5 => "Z. Sun" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/jth.14817" "Revista" => array:6 [ "tituloSerie" => "J Thromb Haemost" "fecha" => "2020" "volumen" => "18" "paginaInicial" => "1094" "paginaFinal" => "1099" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32220112" "web" => "Medline" ] ] ] ] ] ] ] ] 47 => array:3 [ "identificador" => "bib0240" "etiqueta" => "48" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up [published online ahead of print, 2020 Apr 15]" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B. Bikdeli" 1 => "M.V. Madhavan" 2 => "D. Jimenez" 3 => "T. Chuich" 4 => "I. Dreyfus" 5 => "E. Driggin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jacc.2020.04.031" "Revista" => array:3 [ "tituloSerie" => "J Am Coll Cardiol" "fecha" => "2020" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27151352" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735743/0000001700000008/v1_202110061021/S2173574320301337/v1_202110061021/en/main.assets" "Apartado" => array:4 [ "identificador" => "5793" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Special article" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21735743/0000001700000008/v1_202110061021/S2173574320301337/v1_202110061021/en/main.pdf?idApp=UINPBA00004M&text.app=https://reumatologiaclinica.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574320301337?idApp=UINPBA00004M"]

Statistics

Special Article

Therapeutic options for the management of severe COVID-19: A rheumatology perspective

Opciones terapéuticas en el manejo de la COVID-19 grave: una perspectiva de Reumatología

Claudia Mendoza-Pintoa,b, Mario García-Carrascoa,b,

Corresponding author

mgc30591@yahoo.com

Corresponding author.

, Pamela Munguía Realpozob, Socorro Méndez-Martínezc

a Unidad de Investigación de Enfermedades Autoinmunes Sistémicas, Hospital de Especialidades, UMAE-Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Puebla, Mexico

b Departamento de Reumatología e Inmunología, Facultad de Medicina, Benemérita Universidad Autónoma de Puebla, Puebla, Mexico

c Coordinación de Investigación en Salud, Delegación Puebla, Instituto Mexicano del Seguro Social, Puebla, Mexico

Read

8331

Times
was read the article

1611

Total PDF

6720

Total HTML

Share statistics

 array:23 [
  "pii" => "S2173574320301337"
  "issn" => "21735743"
  "doi" => "10.1016/j.reumae.2020.05.002"
  "estado" => "S300"
  "fechaPublicacion" => "2021-10-01"
  "aid" => "1425"
  "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46; and Sociedad Espa&#241;ola de Reumatolog&#237;a y Colegio Mexicano de Reumatolog&#237;a"
  "copyrightAnyo" => "2020"
  "documento" => "article"
  "crossmark" => 1
  "subdocumento" => "fla"
  "cita" => "Reumatol Clin. 2021;17:431-6"
  "abierto" => array:3 [
    "ES" => false
    "ES2" => false
    "LATM" => false
  ]
  "gratuito" => false
  "lecturas" => array:1 [
    "total" => 0
  ]
  "Traduccion" => array:1 [
    "es" => array:19 [
      "pii" => "S1699258X2030108X"
      "issn" => "1699258X"
      "doi" => "10.1016/j.reuma.2020.05.002"
      "estado" => "S300"
      "fechaPublicacion" => "2021-10-01"
      "aid" => "1425"
      "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46; and Sociedad Espa&#241;ola de Reumatolog&#237;a y Colegio Mexicano de Reumatolog&#237;a"
      "documento" => "article"
      "crossmark" => 1
      "subdocumento" => "fla"
      "cita" => "Reumatol Clin. 2021;17:431-6"
      "abierto" => array:3 [
        "ES" => true
        "ES2" => true
        "LATM" => true
      ]
      "gratuito" => true
      "lecturas" => array:1 [
        "total" => 0
      ]
      "es" => array:12 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">Art&#237;culo especial</span>"
        "titulo" => "Opciones terap&#233;uticas en el manejo de la COVID-19 grave&#58; una perspectiva de Reumatolog&#237;a"
        "tienePdf" => "es"
        "tieneTextoCompleto" => "es"
        "tieneResumen" => array:2 [
          0 => "es"
          1 => "en"
        ]
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "431"
            "paginaFinal" => "436"
          ]
        ]
        "titulosAlternativos" => array:1 [
          "en" => array:1 [
            "titulo" => "Therapeutic Options for the Management of Severe COVID-19&#58; A Rheumatology Perspective"
          ]
        ]
        "contieneResumen" => array:2 [
          "es" => true
          "en" => true
        ]
        "contieneTextoCompleto" => array:1 [
          "es" => true
        ]
        "contienePdf" => array:1 [
          "es" => true
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "Claudia Mendoza-Pinto, Mario Garc&#237;a-Carrasco, Pamela Mungu&#237;a Realpozo, Socorro M&#233;ndez-Mart&#237;nez"
            "autores" => array:4 [
              0 => array:2 [
                "nombre" => "Claudia"
                "apellidos" => "Mendoza-Pinto"
              ]
              1 => array:2 [
                "nombre" => "Mario"
                "apellidos" => "Garc&#237;a-Carrasco"
              ]
              2 => array:2 [
                "nombre" => "Pamela"
                "apellidos" => "Mungu&#237;a Realpozo"
              ]
              3 => array:2 [
                "nombre" => "Socorro"
                "apellidos" => "M&#233;ndez-Mart&#237;nez"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "es"
      "Traduccion" => array:1 [
        "en" => array:9 [
          "pii" => "S2173574320301337"
          "doi" => "10.1016/j.reumae.2020.05.002"
          "estado" => "S300"
          "subdocumento" => ""
          "abierto" => array:3 [
            "ES" => false
            "ES2" => false
            "LATM" => false
          ]
          "gratuito" => false
          "lecturas" => array:1 [
            "total" => 0
          ]
          "idiomaDefecto" => "en"
          "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574320301337?idApp=UINPBA00004M"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1699258X2030108X?idApp=UINPBA00004M"
      "url" => "/1699258X/0000001700000008/v1_202109290644/S1699258X2030108X/v1_202109290644/es/main.assets"
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S2173574320300678"
    "issn" => "21735743"
    "doi" => "10.1016/j.reumae.2020.06.003"
    "estado" => "S300"
    "fechaPublicacion" => "2021-10-01"
    "aid" => "1395"
    "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46; and Sociedad Espa&#241;ola de Reumatolog&#237;a y Colegio Mexicano de Reumatolog&#237;a"
    "documento" => "simple-article"
    "crossmark" => 1
    "subdocumento" => "crp"
    "cita" => "Reumatol Clin. 2021;17:437-9"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Brief Report</span>"
      "titulo" => "Psoriasis induced by biological therapy"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "437"
          "paginaFinal" => "439"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Psoriasis inducida por terapia biol&#243;gica"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0005"
          "etiqueta" => "Fig&#46; 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 451
              "Ancho" => 1250
              "Tamanyo" => 96477
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Images of palmoplantar psoriasis in a patient under treatment with anti-TNF&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Lydia Montolio Chiva, &#192;ngels Mart&#237;nez Ferrer, Almudena Mateu Puchades, Cristina Campos Fern&#225;ndez, Javier Narv&#225;ez Garcia, Juan Jos&#233; Alegre Sancho"
          "autores" => array:6 [
            0 => array:2 [
              "nombre" => "Lydia"
              "apellidos" => "Montolio Chiva"
            ]
            1 => array:2 [
              "nombre" => "&#192;ngels"
              "apellidos" => "Mart&#237;nez Ferrer"
            ]
            2 => array:2 [
              "nombre" => "Almudena"
              "apellidos" => "Mateu Puchades"
            ]
            3 => array:2 [
              "nombre" => "Cristina"
              "apellidos" => "Campos Fern&#225;ndez"
            ]
            4 => array:2 [
              "nombre" => "Javier"
              "apellidos" => "Narv&#225;ez Garcia"
            ]
            5 => array:2 [
              "nombre" => "Juan Jos&#233;"
              "apellidos" => "Alegre Sancho"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S1699258X2030019X"
        "doi" => "10.1016/j.reuma.2019.12.005"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1699258X2030019X?idApp=UINPBA00004M"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574320300678?idApp=UINPBA00004M"
    "url" => "/21735743/0000001700000008/v1_202110061021/S2173574320300678/v1_202110061021/en/main.assets"
  ]
  "en" => array:19 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Special Article</span>"
    "titulo" => "Therapeutic options for the management of severe COVID-19&#58; A rheumatology perspective"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "431"
        "paginaFinal" => "436"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Claudia Mendoza-Pinto, Mario Garc&#237;a-Carrasco, Pamela Mungu&#237;a Realpozo, Socorro M&#233;ndez-Mart&#237;nez"
        "autores" => array:4 [
          0 => array:3 [
            "nombre" => "Claudia"
            "apellidos" => "Mendoza-Pinto"
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          1 => array:4 [
            "nombre" => "Mario"
            "apellidos" => "Garc&#237;a-Carrasco"
            "email" => array:1 [
              0 => "mgc30591@yahoo.com"
            ]
            "referencia" => array:3 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
              2 => array:2 [
                "etiqueta" => "&#42;"
                "identificador" => "cor0005"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "Pamela"
            "apellidos" => "Mungu&#237;a Realpozo"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "Socorro"
            "apellidos" => "M&#233;ndez-Mart&#237;nez"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:3 [
          0 => array:3 [
            "entidad" => "Unidad de Investigaci&#243;n de Enfermedades Autoinmunes Sist&#233;micas&#44; Hospital de Especialidades&#44; UMAE-Centro de Investigaci&#243;n Biom&#233;dica de Oriente&#44; Instituto Mexicano del Seguro Social&#44; Puebla&#44; Mexico"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Departamento de Reumatolog&#237;a e Inmunolog&#237;a&#44; Facultad de Medicina&#44; Benem&#233;rita Universidad Aut&#243;noma de Puebla&#44; Puebla&#44; Mexico"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Coordinaci&#243;n de Investigaci&#243;n en Salud&#44; Delegaci&#243;n Puebla&#44; Instituto Mexicano del Seguro Social&#44; Puebla&#44; Mexico"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Opciones terap&#233;uticas en el manejo de la COVID-19 grave&#58; una perspectiva de Reumatolog&#237;a"
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The degree of disease severity with COVID-19 varies and can become fulminant or fatal&#46; The World Health Organization &#40;WHO&#41; estimates that severe disease can occur in about 13&#46;8&#37; of cases and 6&#46;1&#37; are critical&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> When cases are fulminant&#44; patients may develop sepsis&#44; acute respiratory failure syndrome &#40;ARDS&#41; or multiple organ failure&#44; which are not exclusive to coronaviruses&#46; Cytokine release syndrome &#40;CRS&#41; refers to an uncontrolled and exaggerated release of pro-inflammatory mediators into the activated immune system&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> This disturbance may be present in various clinical entities&#44; including the rheumatology setting&#44; Still&#39;s disease&#44; systemic juvenile idiopathic arthritis&#44; systemic lupus erythematosus and catastrophic antiphospholipid syndrome &#40;APS&#41;&#46; CRS is involved in the immunopathogenesis of many pathological processes&#44; such as ARDS&#44; sepsis&#44; Macrophage activation syndrome &#40;MAS&#41;&#44; etc&#46;&#44; several of which are described in severe acute respiratory syndrome &#40;SARS&#41;&#44; Middle East respiratory syndrome &#40;MERS&#41; and also in the new COVID-19 infection&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> While treatment directed against the virus is desired&#44; treatment of the systemic response is possibly the most important aspect of patient care and should be viewed aggressively&#46; Finally&#44; patients with COVID-19 who develop a severe condition may have a procoagulant pattern&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Therefore&#44; this review synthesizes the evidence related to therapies with an anti-inflammatory role that can play a relevant role in the management of patients with severe COVID-19&#44; briefly mentioning the role of antithrombotic therapy in the treatment of complicated patients&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Glucocorticoids</span><p id="par0010" class="elsevierStylePara elsevierViewall">Glucocorticoids &#40;GC&#41; are some of the most widely used anti-inflammatory agents&#59; they are commonly prescribed in the treatment of patients with COVID-19 &#40;72&#37; in the ICU&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> However&#44; as mentioned in the Chinese COVID-19 guidelines&#44;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> physicians must be careful in the use of GCs because of their uncertain benefits in the context of viral respiratory infection&#46; Several studies have reported inferior results in SARS patients treated with GC&#44;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> due to delayed purging of the virus&#46; Other concerns with GCs are short-term and long-term adverse effects&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antimalarials &#40;chloroquine and hydroxychloroquine&#41;</span><p id="par0015" class="elsevierStylePara elsevierViewall">Recent publications have drawn attention to the possible beneficial effect of hydroxychloroquine &#40;HCQ&#41; and chloroquine &#40;CLQ&#41; in the treatment of patients infected with the new SARS-CoV-2 coronavirus&#46; It has been observed that the growth of several different viruses &#40;including SARS coronavirus&#41; can be inhibited in cell cultures by both CLQ and HCQ&#46; In addition&#44; these drugs are weak bases that can affect acidic vesicles and inhibit several enzymes&#46; This characteristic enables inhibiting of viral entry into cells when endocytosis is pH dependent&#46; They also inhibit the enzyme glycosyltransferase &#40;inhibition of virus glycosylation&#41;&#44; post-transcriptional viral modifications and replication of some viral families&#46; As it is known that COVID-19 infection can on occasion lead to severe pictures with SARS&#44; which can be due in part to the increase of proinflammatory cytokines such as interleukin 6 &#40;IL-6&#41; and tumour necrosis factor-alpha &#40;TNF-&#945;&#41;&#46; CLQ is highly effective in combination with remdesivir in controlling SARS-CoV-2<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> in vitro&#46; There is now already some evidence in humans&#46; In an open observational study conducted in France&#44; they evaluated the role of HCQ in combination with azithromycin on respiratory viral load in 20 patients with COVID-19 compared with 16 controls&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> A significant reduction in viral load was shown &#40;70&#37; at day 7&#41; compared to the controls&#46; When azithromycin was added&#44; more efficient elimination of the virus was found &#40;100&#37; reduction&#41;&#46; Gao et al&#46; described results in 100 patients in China where they demonstrated the superiority of CLQ over the control treatment in inhibiting exacerbation of pneumonia&#44; improving lung imaging findings&#44; promoting negative virus conversion&#44; and shortening the course of the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> However&#44; the details of this study are not known in depth&#46; A recent study reported the results of a retrospective analysis of 368 hospitalized patients with confirmed SARS-CoV-2 infection &#40;U&#46;S&#46; Veterans Health Administration&#41; of evaluation of exposure to HCQ alone or in combination with azithromycin&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> The mortality rates in the HCQ alone&#44; combined HQC&#44; and no HQC groups were 27&#46;8&#37;&#44; 22&#46;1&#37;&#44; and 11&#46;4&#37;&#44; respectively&#46; Ventilation rates in the HCQ&#44; combined HCQ and no HCQ groups were 13&#46;3&#37;&#44; 6&#46;9&#37; and 14&#46;1&#37;&#44; respectively&#46; In this study&#44; no evidence was found that the use of HCQ alone or combined reduces the risk of mechanical ventilation in hospitalized patients with COVID-19 and that patients receiving HCQ alone had the highest mortality rate&#46; These findings highlight the importance of waiting for the results of the prospective randomized studies that are underway before widely adopting these drugs&#46; There are currently about 14 clinical trials registered to prove the benefit of antimalarials&#46; Although antimalarials are relatively safe drugs&#44; it should be remembered that their most frequent effects are gastrointestinal&#44; pruritus&#44; and dermal changes in 10&#37; of patients&#46; The most serious effects are of low incidence&#44; such as cardiomyotoxicity&#44; neuromyopathy&#44; and irreversible retinopathy &#40;large doses and long term&#41;&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Tocilizumab&#44; inleukin-6 inhibitor</span><p id="par0020" class="elsevierStylePara elsevierViewall">There has recently been much interest in the possibility of using tocilizumab&#44; a humanized antibody targeting the IL-6 receptor&#44; on the grounds of preventing or treating the cytokine storm that has been observed in patients that progress to cardiovascular collapse&#44; multiorgan dysfunction&#44; and death&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Inflammatory cytokines and chemokines&#44; including IL-6&#44; IL-1&#946;&#44; induced protein 10&#44; and monocyte chemotactic protein-1&#44; have been found to be significantly elevated in Covid-19 patients&#44; and are more often elevated in severe patients than in non-severe patients&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> In patients with COVID-19&#44; with elevated inflammatory cytokines&#44; post mortem pathology revealed tissue necrosis and infiltrations of macrophages and monocytes in the lung&#44; heart and gastrointestinal mucosa&#44;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> which suggests an uncontrolled immune response&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Studies have shown that ARDS occurs in some SARS patients despite a reduced viral load&#44; suggesting that an exuberant immune response rather than viral virulence is possibly responsible for the pathology at tissue level&#46; Therefore&#44; antiviral therapy alone may not be sufficient&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> As previously mentioned&#44; IL-6 is one of the cytokines that plays a role in the pathogenesis in patients with severe COVID-19&#59; it has also been suggested as a biomarker of severe disease&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> and therefore blockade may be a promising strategy for COVID-19-induced CRS&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">IL-6 is essential for the generation of T-helper 17 &#40;Th17&#41; lymphocytes in the interaction between T-lymphocytes and dendritic cells&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Therefore elevated IL-6 may explain the excessive Th17 activation observed in patients with COVID-19&#44; as reported by Xu et al&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Although no data are available on IL-6 blockade in CRS induced by viral infection&#44; animal studies of SARS-CoV have shown that they inhibit nuclear factor kappa-B&#44; an essential transcription factor of IL-6&#44; increasing animal survival with reduced levels of IL-6&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> Tocilizumab&#44; which blocks IL-6&#44; binds to the IL-6 receptor in both soluble and membrane-bound forms to inhibit IL-6-mediated signals&#46; This drug has been approved by the Food and Drug Administration for the treatment of CRS associated with CAR T-cell therapy&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Data on the use of this molecule in the treatment of SARS-CoV-2 infection are still preliminary but promising results have prompted the Chinese Health Commission to update its national guidelines&#44; which include tocilizumab for the treatment of severe COVID-19&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> The Italian guidelines also support the use of tocilizumab &#40;at a dose of 8&#8239;mg&#47;kg&#44; with a second dose 12&#8239;h after the first and a possible third after 24-36&#8239;h&#44; depending on the clinical response&#41;&#44; in the event of rapid clinical or radiological worsening&#44; after excluding contraindications to its use &#40;levels of transaminases &#62;5 times the upper limit of normal&#44; neutrophil count &#60;50&#44;000 cells&#47;&#956;l&#44; presence of documented sepsis complicated by bacteria&#44; diverticulitis&#47;intestinal perforation&#44; skin infection&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">There are case reports of improvement in patients with severe COVID-19 after the administration of tocilizumab&#46;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">21&#44;22</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Interleukin 1b inhibitors and protein kinase inhibitors JAK1&#47;2 &#40;roxulitinib&#41;</span><p id="par0045" class="elsevierStylePara elsevierViewall">Several laboratory markers related to MAS&#47; haemaphagocytic lymphohistiocytosis &#40;HLH&#41; are elevated in severe COVID-19&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> Therefore&#44; treatments aimed at controlling MAS&#47;HLH have been suggested for the management of severe COVID-19&#46; The recombinant human IL-1 receptor antagonist&#44; anakinra&#44; has been used for the treatment of MAS&#47;HLH associated with autoimmune rheumatic diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> Data from a reanalysis of a phase <span class="elsevierStyleSmallCaps">iii</span> controlled trial found that anakinra was associated with significant improvement in the survival of patients with sepsis with concurrent MAS&#47;HLH&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Small molecule inhibiting Janus kinases&#44; such as the JAK1&#47;2 inhibitor ruxolitinib&#44;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> are capable of blocking signals from IL-6&#44; interferon &#947; &#40;IFN-&#947;&#41; and other cytokines involved in MAS&#47;HLH&#46; Therefore&#44; this drug could have potential in the treatment of serious complications in patients with COVID-19&#46; More recently&#44; the use of anti-IFN-&#947; antibodies has been contemplated in the management of this serious complication&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Intravenous immunoglobulin and plasma from recovered patients &#40;&#8220;convalescent plasma&#8221;&#41;</span><p id="par0055" class="elsevierStylePara elsevierViewall">Individuals with a weakened immune system appear to be at greater risk of developing complications associated with COVID-19&#46; Immunotherapy using IgG in combination with antiviral drugs could be used to treat or prevent SARS-CoV-2 infection and strengthen our immune system against this virus&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28&#44;29</span></a> They have also have been administered as anti-infective agents against viruses&#44; bacteria and fungi in experimental models and in humans&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> IVIGs can modulate the immune response by several mechanisms&#44; including blocking various pro-inflammatory cytokines&#44; Fc receptors&#44; and leukocyte adhesion molecules&#44; suppressing Th1 and Th17 cell subtypes&#44; and neutralizing pathogenic autoantibodies&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> IVIGs can also expand regulatory T lymphocytes&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> However&#44; IVIGs have adverse reactions&#46; During the SARS outbreak in 2003&#44; IVIG was used extensively in Singapore&#46; However&#44; some critically ill patients developed venous thromboembolism &#40;VTE&#41; including pulmonary embolism despite the use of prophylactic low molecular weight heparin&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> This is due to the increased viscosity in hypercoagulable states of SARS patients&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Convalescent plasma samples have been used to treat SARS in Hong Kong and China and may be valuable because&#44; unlike standard IVIG preparations&#44; they have high levels of anti-SARS-CoV antibodies&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> Pyrc et al&#46; showed that human serum from adult humans inhibited infection by HCov-NL63&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> Furthermore&#44; they described that IVIGs can also neutralize HCoV-NL63&#46; Boukhvalova et al&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> demonstrated that&#44; in contrast&#44; the commercially available therapeutic polyclonal IgG products&#44; IVIG obtained from donors with antibodies at high titres against respiratory syncytial virus &#40;RSV&#41;&#44; have great potential in improving RSV outcomes in immunocompromised subjects&#44; not only controlling viral replication&#44; but also reducing damage to the lung parenchyma and the epithelial lining of the respiratory tract&#46; The use of convalescent plasma or serum was also suggested by the WHO under the Blood Regulators Network should vaccines and antiviral drugs not be available in an emerging virus&#46; In the current pandemic&#44; there are reports that convalescent plasma has been used in China to treat patients with COVID-19&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> In a pilot study of 10 patients with severe COVID-19&#44; investigators collected convalescent plasma with neutralizing antibody titres at a dilution of 1&#58;640 or more&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> The convalescent plasma transfusion resulted in no serious adverse events in the receivers&#46; All 10 patients had improvement of symptoms &#40;e&#46;g&#46;&#44; fever&#44; cough&#44; shortness of breath&#44; and precordial pain&#41; within 1-3 days of the transfusion&#59; they also showed radiological improvement in lung lesions&#46; Similarly&#44; an undetectable viral load was found in most of them&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">IgG immunotherapy could be used to neutralize the virus causing COVID-19&#46; The efficiency of IgG could be improved if these immune IgG antibodies were collected from patients who had recovered from COVID-19 in the same city&#44; or surrounding areas&#44; as donor subjects who have dealt with the virus&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Plasma interchange</span><p id="par0070" class="elsevierStylePara elsevierViewall">Therapeutic apheresis encompasses a large number of techniques the main basis of which is to process a patient&#39;s blood through an extracorporeal device with the aim of eliminating antibodies and preformed immunocomplexes to prevent tissue damage&#44; eliminating inflammation mediators as a complement and cytokines that could contribute to damage&#44; and providing deficiency factors&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> Among the different types of apheresis&#44; some of the most used are therapeutic plasma exchange &#40;PE&#41; and immunoadsorption&#46; Therapeutic PE is a technique for purifying extracorporeal blood&#44; through which plasma is removed&#46; A variable volume of plasma is removed from the patient and replaced with replacement solutions that maintain volume and oncotic pressure&#46; The term &#34;plasmapheresis&#34; should be reserved for situations in which only plasma removal without replenishment is performed&#44; such as plasma donation by apheresis for transfusion or subsequent industrial plasma fractionation&#46; This procedure extracts less plasma &#40;around 600&#8239;ml&#41;&#44; without replenishment solution&#44; in less time and with simpler separation techniques than those used in PE&#46; The host response to infection has been described and involves a complex interaction of cytokine storm&#44; inflammation&#44; endothelial dysfunction&#44; and pathological coagulation&#46; Plasma exchange is a pathway that offers benefit at multiple levels by removing inflammatory cytokines&#44; stabilizing endothelial membranes&#44; and restarting the hypercoagulable state&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Busund et al&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> showed a trend towards improving mortality with therapeutic PE as an adjuvant treatment in adults with sepsis and multiple organ failure in a controlled clinical trial&#44; while a meta-analysis by Rimmer also showed benefit in adult patient mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a> Addressing this information&#44; Patel et al&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> used therapeutic PE during the 2009 A &#40;H1N1&#41; influenza epidemic in 3 paediatric patients with a fulminant condition similar to the current pandemic&#46; All 3 patients developed ARDS with haemodynamic compromise that continued to deteriorate despite rescue treatment for ARDS including inhaled nitric oxide and extracorporeal venous membrane oxygenation&#46; All 3 patients made a full recovery from their disease after receiving rescue PE&#46; Recently&#44; 3 patients were described with COVID-19 in Wuhan&#44; China&#44;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> characterized by deep inflammation and treated with blood purification therapies&#44; including PE and adsorption&#46; A potent effect on cytokine storm management and pathogenic antibodies was shown&#46; Of these 3 patients&#44; 2 maintained a stable state and could be discharged from the Intensive Care Unit&#44; while one developed disseminated intravascular coagulation &#40;DIC&#41; and died&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Antithrombotic therapy</span><p id="par0080" class="elsevierStylePara elsevierViewall">Severe COVID-19 can often present a marked elevation of D-dimer&#44; thrombocytopenia and coagulation disturbances that are considered to be regulated by various inflammatory cytokines<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">43&#44;44</span></a> and that correlate with mortality&#46; Another biomarker that has been found to be elevated in patients with severe COVID-19 is ferritin&#44;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> which is also impaired in other severe conditions&#44; including APS in its most severe form&#44; catastrophic APS&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a> Recently&#44; a group from China described 3 cases with COVID-19 and antiphospholipid antibodies&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a> Recent statements by the International Society on Thrombosis and Haemostasis &#40;ISTH&#41; and the American Society of Hematology &#40;ASH&#41; suggest that all patients hospitalized with COVID-19 should receive thromboprophylaxis or full-dose therapeutic anticoagulation&#46; The efficacy of anticoagulation therapy in patients with COVID-19 was recently evaluated retrospectively&#46; Lower mortality at 28 days was found in patients who used heparin &#40;40&#37;&#41; compared to those who did not &#40;64&#46;2&#37;&#41;&#44; mainly in those with sepsis-induced coagulopathy or with a markedly elevated D-dimer&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> summarizes the antithrombotic recommendations for patients with COVID-19&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Conclusions</span><p id="par0085" class="elsevierStylePara elsevierViewall">COVID-19 is a viral infection with potentially serious complications that can increase the risk of death in infected patients&#46; Several of these disturbances are secondary to an uncontrolled immune response where a cytokine storm plays a similarly important role in preventing the thrombotic complications to which these patients are exposed&#46; Although antiviral treatment and respiratory support therapies are essential in the treatment of severe cases&#44; it is necessary to assess the risk-benefit of therapies aimed at controlling the immune response to decrease the mortality rate&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Funding</span><p id="par0095" class="elsevierStylePara elsevierViewall">This research study has received no specific support from public sector agencies&#44; the commercial sector&#44; or non-profit entities&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Conflict of interests</span><p id="par0090" class="elsevierStylePara elsevierViewall">The authors have no conflict of interests to declare</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:16 [
        0 => array:3 [
          "identificador" => "xres1584153"
          "titulo" => "Abstract"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0005"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1425603"
          "titulo" => "Keywords"
        ]
        2 => array:3 [
          "identificador" => "xres1584154"
          "titulo" => "Resumen"
          "secciones" => array:1 [
            0 => array:1 [
              "identificador" => "abst0010"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec1425602"
          "titulo" => "Palabras clave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Glucocorticoids"
        ]
        6 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Antimalarials &#40;chloroquine and hydroxychloroquine&#41;"
        ]
        7 => array:2 [
          "identificador" => "sec0020"
          "titulo" => "Tocilizumab&#44; inleukin-6 inhibitor"
        ]
        8 => array:2 [
          "identificador" => "sec0025"
          "titulo" => "Interleukin 1b inhibitors and protein kinase inhibitors JAK1&#47;2 &#40;roxulitinib&#41;"
        ]
        9 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Intravenous immunoglobulin and plasma from recovered patients &#40;&#8220;convalescent plasma&#8221;&#41;"
        ]
        10 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "Plasma interchange"
        ]
        11 => array:2 [
          "identificador" => "sec0040"
          "titulo" => "Antithrombotic therapy"
        ]
        12 => array:2 [
          "identificador" => "sec0045"
          "titulo" => "Conclusions"
        ]
        13 => array:2 [
          "identificador" => "sec0055"
          "titulo" => "Funding"
        ]
        14 => array:2 [
          "identificador" => "sec0050"
          "titulo" => "Conflict of interests"
        ]
        15 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2020-04-28"
    "fechaAceptado" => "2020-05-08"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1425603"
          "palabras" => array:3 [
            0 => "COVID-19"
            1 => "Coronavirus"
            2 => "Cytokine release syndrome"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1425602"
          "palabras" => array:3 [
            0 => "COVID-19"
            1 => "Coronavirus"
            2 => "S&#237;ndrome de liberaci&#243;n de citocinas"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The novel SARS-CoV-2 human coronavirus in Wuhan&#44; China&#44; has triggered a worldwide respiratory disease outbreak &#40;COVID-19&#41;&#46; Acute respiratory distress syndrome &#40;ARDS&#41;&#44; multiorgan dysfunction and thrombotic events are among the leading causes of death in critically ill patients with COVID-19&#46; The elevated inflammatory cytokines suggest that a &#8220;cytokine storm&#8221;&#44; also known as cytokine release syndrome &#40;CRS&#41;&#44; may play a major role in the pathology of COVID-19&#46; In addition to anti-viral therapy and supportive treatment in critically ill patients&#44; unique medications for this condition are also under investigation&#46; Here we reviewed therapeutic options&#44; including the antibody therapy that might be an immediate strategy for SARS-CoV-2 therapy&#46;</p></span>"
      ]
      "es" => array:2 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">El inicio del nuevo coronavirus humano del s&#237;ndrome respiratorio agudo grave &#40;SARS-Cov-2&#41; en Wuhan&#44; China&#44; ha desencadenado un brote respiratorio mundial &#40;COVID-19&#41;&#46; El s&#237;ndrome de insuficiencia respiratoria agua &#40;SIRA&#41;&#44; el fallo multiorg&#225;nico y eventos tromb&#243;ticos est&#225;n entre las causas que llevan a la muerte en pacientes cr&#237;ticamente enfermos con COVID-19&#46; Las citocinas inflamatorias elevadas sugieren que una &#8220;tormenta de citocinas&#8221;&#44; tambi&#233;n conocida como s&#237;ndrome de liberaci&#243;n de citocinas &#40;SLC&#41;&#44; puede jugar un papel principal en la patolog&#237;a de COVID-19&#46; Adicionalmente al tratamiento anti-viral y la terapia de apoyo respiratorio en pacientes cr&#237;ticamente enfermos&#44; est&#225;n en investigaci&#243;n medicamentos &#250;nicos para esta condici&#243;n&#46; En esta revisi&#243;n sintetizamos la evidencia m&#225;s actual de opciones terap&#233;uticas&#44; incluyendo anticuerpos anti-citocinas como una estrategia intermedia para la terapia de SARS-Cov-2&#46;</p></span>"
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Mendoza-Pinto C&#44; Garc&#237;a-Carrasco M&#44; Mungu&#237;a Realpozo P&#44; M&#233;ndez-Mart&#237;nez S&#46; Opciones terap&#233;uticas en el manejo de la COVID-19 grave&#58; una perspectiva de Reumatolog&#237;a&#46; Reumatol Clin&#46; 2021&#59;17&#58;431&#8211;436&#46;</p>"
      ]
    ]
    "multimedia" => array:1 [
      0 => array:9 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "fuente" => "Source&#58; Bikdeli et al&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">48</span></a>"
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0005"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">DOA&#58; direct oral anticoagulants&#59; DIC&#58; disseminated intravascular coagulation&#59; LMWH&#58; low molecular weight heparin&#59; INR&#58; international normalized ratio&#59; VTE&#58; venous thromboembolism&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Patients with mild COVID-19 &#40;outpatient&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>For outpatients with COVID-19&#44; increased mobility should be encouraged&#46; Although indiscriminate use of pharmacological VTE prophylaxis should not be pursued&#44; assessment for the risk of VTE and of bleeding is reasonable&#46; Pharmacologic prophylaxis could be considered after risk assessment on an individual case basis for patients who have elevated risk VTE&#44; without high bleeding risk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>There is no known risk of developing severe COVID-19 due to taking antithrombotic agents &#40;i&#46;e&#46;&#44; antiplatelet agents or anticoagulants&#41;&#46; If patients were taking antithrombotic agents for prior known thrombotic disease&#44; they should continue their antithrombotic therapy as recommended&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>For patients on vitamin K antagonists who do not have recent stable INRs&#44; and are unable to undergo INR testing&#44; it is reasonable to transition the treatment DOACs if there are no contraindications and no problems with drug availability&#46; If DOACs are not approved or available&#44; LMWH &#40;enoxaparin 40&#8239;mg&#47;day&#41; can be considered&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Patients with moderate or severe COVID-19 without DIC hospitalised</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Hospitalized patients with COVID-19 should undergo risk stratification for VTE prophylaxis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>For hospitalized patients with COVID-19 and not in DIC&#44; prophylactic doses of anticoagulation should be administered to prevent VTE &#40;enoxaparin 40&#8239;mg&#47;day or dalteparin 5000 U daily&#59; subcutaneous heparin 5000 U twice daily may be considered for patients with kidney failure &#91;e&#46;g&#46;&#44; creatinine clearance &#60;30&#8239;ml&#47;min&#93;&#41;&#46; If pharmacological prophylaxis is contraindicated&#44; it is reasonable to consider intermittent pneumatic compression&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>For hospitalised patients with COVID-19 and not in DIC&#44; there are insufficient data to consider routine therapeutic or parenteral therapeutic doses with LMWH &#40;e&#46;g&#46;&#44; enoxaparin 1&#8239;mg&#47;kg&#47;day&#44; or enoxaparin 40&#8239;mg twice a day&#41; or unfractionated heparin &#40;with an activated PTT target of 50&#8722;70&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Routine screening for VTE is not recommended &#40;e&#46;g&#46;&#44; bilateral lower extremity ultrasound&#41; for hospitalized patients with COVID-19 with elevated D-dimer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Patients with moderate to severe COVID-19 hospitalised and suspected DIC</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>For patients with moderate to severe COVID-19 and in DIC but without overt bleeding&#44; prophylactic anticoagulation should be administered&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>For hospitalized patients with COVID-19 with suspected or confirmed DIC with no overt bleeding&#44; there are insufficient data to consider routine therapeutic-dose parenteral anticoagulation at therapeutic doses with LMWH or unfractionated heparin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>For patients with moderate or severe COVID-19 on chronic therapeutic anticoagulation&#44; who develop suspected or confirmed DIC without overt bleeding&#44; it is reasonable to consider the indication for anticoagulation and to weigh with risk of bleeding when making clinical decisions regarding dose adjustments or discontinuation&#46; It is recommended to reduce the intensity of anticoagulation in this clinical circumstance&#44; unless the risk of thrombosis is considered to be exceedingly high&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>For patients with moderate or severe COVID-19 and an indication for dual antiplatelet therapy &#40;e&#46;g&#46;&#44; percutaneous coronary intervention in the past 3 months or recent myocardial infarction&#41; and with suspected or confirmed DIC with no overt bleeding&#44; in the absence of evidence&#44; decisions for antiplatelet therapy need to be individualized&#46; In general&#44; it is reasonable to continue dual antiplatelet therapy &#40;aspirin plus a P2Y receptor inhibitor such as clopidogrel&#41; if platelet count is &#62;50&#44;000&#44; reduce to a single therapy if platelet count is 25&#44;000 and 50&#44;000&#44; and discontinue if platelet count is &#60;25&#44;000&#46; However&#44; these guidelines may be revised depending on the individualized relative risk of thrombotic complications vs&#46; bleeding&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>For patients who were admitted and are now being discharged for COVID-19 and now discharged&#44; routine screening for VTE risk is reasonable for consideration of pharmaceutical prophylaxis for up to 45 days post-discharge&#46; Pharmacological prophylaxis should be considered if there is elevated risk for thrombotic events&#44; without bleeding risk&#46; Ambulation and physical activity should be encouraged&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Patients without COVID-19 who have previously known thrombotic disease</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>There is no known risk of developing COVID-19 due to the administration of antithrombotic agents&#46; Patients should continue treatment with antithrombotic agent as recommended&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>To minimize risks associated with health care worker and patient in-person interactions&#44; follow-up with e&#46;visits and telemedicine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Patients without COVID-19 who develop new thrombotic disease</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>To minimize the risks associated with health care worker and patient in-person interactions&#44; in-home treatment or early discharge should be prioritized with electronic or telemedicine follow-up&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleItalic">Patients without COVID-19 but with comorbid conditions &#40;e&#46;g&#46;&#44; prior history of VTE&#44; active cancer&#44; major lung disease&#41; who are homebound</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Recommendations include increased mobility&#44; and risk assessment for the risk of VTE and risk of bleeding is reasonable&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Administration of pharmacological prophylaxis could be considered after risk assessment on an individual case basis based on their risk for thrombosis and bleeding risk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2713338.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Summary of the consensus on recommendations for antithrombotic therapy during the COVID-19 pandemic&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:48 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Aylward&#44; Bruce &#40;WHO&#41;&#59; Liang W &#40;PRC&#41;&#46; Report of the WHO-China JointMission on Coronavirus Disease 2019 &#40;COVID-19&#41;&#46; WHO-China Jt Mis-sion Coronavirus Dis 2019 &#91;Internet&#93;&#46; 2020&#59;2019&#40;February&#41;&#58;16&#8211;24&#46; Available from&#58; <a target="_blank" href="https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mission-on-covid-19-final-report.pdf">https&#58;&#47;&#47;www&#46;who&#46;int&#47;docs&#47;default-source&#47;coronaviruse&#47;who-china-joint-mission-on-covid-19-final-report&#46;pdf</a>&#46;"
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Current concepts in the diagnosis and management of cytokine release syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46;W&#46; Lee"
                            1 => "R&#46; Gardner"
                            2 => "D&#46;L&#46; Porter"
                            3 => "C&#46;U&#46; Louis"
                            4 => "N&#46; Ahmed"
                            5 => "M&#46; Jensen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Blood&#46;"
                        "fecha" => "2014"
                        "volumen" => "124"
                        "paginaInicial" => "188"
                        "paginaFinal" => "195"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan&#44; China &#91;published online ahead of print&#44; 2020 Mar 13&#93;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Wu"
                            1 => "X&#46; Chen"
                            2 => "Y&#46; Cai"
                            3 => "J&#46; Xia"
                            4 => "X&#46; Zhou"
                            5 => "S&#46; Xu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jamainternmed.2020.0994.4"
                      "Revista" => array:3 [
                        "tituloSerie" => "JAMA Intern Med"
                        "fecha" => "2020"
                        "paginaInicial" => "e200994"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Incidence of thrombotic complications in critically ill ICU patients with COVID-19"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46;A&#46; Klok"
                            1 => "M&#46; Kruip"
                            2 => "N&#46;J&#46;M&#46; van der Meer"
                            3 => "M&#46;S&#46; Arbous"
                            4 => "D&#46;A&#46;M&#46;P&#46;J&#46; Gommers"
                            5 => "K&#46;M&#46; Kant"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:1 [
                      "Revista" => array:2 [
                        "tituloSerie" => "Thromb Res &#91;Internet&#93;"
                        "fecha" => "2020"
                      ]
                    ]
                    1 => array:1 [
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;linkinghub&#46;elsevier&#46;com&#47;retrieve&#47;pii&#47;S0049384820301201"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan&#44; China"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46; Wang"
                            1 => "B&#46; Hu"
                            2 => "C&#46; Hu"
                            3 => "F&#46; Zhu"
                            4 => "X&#46; Liu"
                            5 => "J&#46; Zhang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jama.2020.1585"
                      "Revista" => array:6 [
                        "tituloSerie" => "JAMA"
                        "fecha" => "2020"
                        "volumen" => "323"
                        "paginaInicial" => "1061"
                        "paginaFinal" => "1069"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32031570"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus &#40;2019-nCoV&#41; infected pneumonia &#40;standard version&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Y&#46;-H&#46; Jin"
                            1 => "L&#46; Cai"
                            2 => "Z&#46;-S&#46; Cheng"
                            3 => "Z&#46;-S&#46; Cheng"
                            4 => "T&#46; Deng"
                            5 => "Y&#46;-P&#46; Fan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s40779-020-0233-6"
                      "Revista" => array:5 [
                        "tituloSerie" => "Mil Med Res"
                        "fecha" => "2020"
                        "volumen" => "7"
                        "paginaInicial" => "4"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32029004"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "C&#46;D&#46; Russell"
                            1 => "J&#46;E&#46; Millar"
                            2 => "J&#46;K&#46; Baillie"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(20)30317-2"
                      "Revista" => array:5 [
                        "tituloSerie" => "Lancet &#91;Internet&#93;"
                        "fecha" => "2020"
                        "volumen" => "395"
                        "paginaInicial" => "473"
                        "paginaFinal" => "475"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus &#40;2019-nCoV&#41; in vitro"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Wang"
                            1 => "R&#46; Cao"
                            2 => "L&#46; Zhang"
                            3 => "X&#46; Yang"
                            4 => "J&#46; Liu"
                            5 => "M&#46; Xu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/s41422-020-0282-0"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cell research"
                        "fecha" => "2020"
                        "volumen" => "30"
                        "paginaInicial" => "269"
                        "paginaFinal" => "271"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32020029"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hydroxychloroquine and azithromycin as a treatment of COVID-19&#58; results of an open-label non-randomized clinical trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P&#46; Gautret"
                            1 => "J&#46;-C&#46; Lagier"
                            2 => "P&#46; Parola"
                            3 => "V&#46;T&#46; Hoang"
                            4 => "L&#46; Meddeb"
                            5 => "M&#46; Mailhe"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:2 [
                        "tituloSerie" => "Int J Antimicrob Agents"
                        "fecha" => "2020"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Breakthrough&#58; chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "J&#46; Gao"
                            1 => "Z&#46; Tian"
                            2 => "X&#46; Yang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.5582/bst.2020.01047"
                      "Revista" => array:6 [
                        "tituloSerie" => "Biosci Trends"
                        "fecha" => "2020"
                        "volumen" => "14"
                        "paginaInicial" => "72"
                        "paginaFinal" => "73"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32074550"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Outcomes of hydroxychloroquine usage&#8239;&#8239;in United States veterans hospitalized with Covid-19"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Magagnoli"
                            1 => "S&#46; Narendran"
                            2 => "F&#46; Pereira"
                            3 => "T&#46; Cummings"
                            4 => "J&#46;W&#46; Hardin"
                            5 => "S&#46;S&#46; Sutton"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:2 [
                        "tituloSerie" => "medRxiv &#91;Internet&#93;"
                        "fecha" => "2020"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan&#44; China&#58; a descriptive study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Chen"
                            1 => "M&#46; Zhou"
                            2 => "X&#46; Dong"
                            3 => "J&#46; Qu"
                            4 => "F&#46; Gong"
                            5 => "Y&#46; Han"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(20)30211-7"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2020"
                        "volumen" => "395"
                        "paginaInicial" => "507"
                        "paginaFinal" => "513"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32007143"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Characteristics of lymphocyte subsets and cytokines in peripheral blood of 123 hospitalized patients with 2019 novel coronavirus pneumonia &#40;NCP&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Wan"
                            1 => "Q&#46; Yi"
                            2 => "S&#46; Fan"
                            3 => "J&#46; Lv"
                            4 => "X&#46; Zhang"
                            5 => "L&#46; Guo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:1 [
                      "Revista" => array:2 [
                        "tituloSerie" => "medRxiv &#91;Internet&#93;"
                        "fecha" => "2020"
                      ]
                    ]
                    1 => array:1 [
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;medrxiv&#46;org&#47;content&#47;early&#47;2020&#47;02&#47;12&#47;2020&#46;02&#46;10&#46;20021832&#46;abstract"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pathological findings of COVID-19 associated with acute respiratory distress syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Z&#46; Xu"
                            1 => "L&#46; Shi"
                            2 => "Y&#46; Wang"
                            3 => "J&#46; Zhang"
                            4 => "L&#46; Huang"
                            5 => "C&#46; Zhang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Lancet Resp Med"
                        "fecha" => "2020"
                        "volumen" => "8"
                        "paginaInicial" => "420"
                        "paginaFinal" => "422"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0075"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia&#58; a prospective study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;S&#46;M&#46; Peiris"
                            1 => "C&#46;M&#46; Chu"
                            2 => "V&#46;C&#46;C&#46; Cheng"
                            3 => "K&#46;S&#46; Chan"
                            4 => "I&#46;F&#46;N&#46; Hung"
                            5 => "L&#46;L&#46;M&#46; Poon"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/s0140-6736(03)13412-5"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2003"
                        "volumen" => "361"
                        "paginaInicial" => "1767"
                        "paginaFinal" => "1772"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12781535"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diagnostic utility of clinical laboratory data determinations for patients with the severe COVID-19"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Y&#46; Gao"
                            1 => "T&#46; Li"
                            2 => "M&#46; Han"
                            3 => "X&#46; Li"
                            4 => "D&#46; Wu"
                            5 => "Y&#46; Xu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/jmv.25770"
                      "Revista" => array:2 [
                        "tituloSerie" => "J Med Virol&#46;"
                        "fecha" => "2020"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Immunotherapeutic implications of IL-6 blockade for cytokine storm"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "T&#46; Tanaka"
                            1 => "M&#46; Narazaki"
                            2 => "T&#46; Kishimoto"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2217/imt-2016-0020"
                      "Revista" => array:6 [
                        "tituloSerie" => "Immunotherapy"
                        "fecha" => "2016"
                        "volumen" => "8"
                        "paginaInicial" => "959"
                        "paginaFinal" => "970"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27381687"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inhibition of NF-kappaB-mediated inflammation in severe acute respiratory syndrome coronavirus-infected mice increases survival"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;L&#46; DeDiego"
                            1 => "J&#46;L&#46; Nieto-Torres"
                            2 => "J&#46;A&#46; Regla-Nava"
                            3 => "J&#46;M&#46; Jimenez-Guardeno"
                            4 => "R&#46; Fernandez-Delgado"
                            5 => "C&#46; Fett"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1128/JVI.02576-13"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Virol"
                        "fecha" => "2014"
                        "volumen" => "88"
                        "paginaInicial" => "913"
                        "paginaFinal" => "924"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24198408"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diagnosis and treatment protocol for novel coronavirus pneumonia&#46;Trial Version 7 &#40;Released by National Health Commission &#38; National Administra-tion of Traditional Chinese Medicine on March 3&#44; 2020&#41;&#46; Diagnosis and TreatmentProtocol for Novel Coronavirus Pneumonia &#40;Trial Version 7&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "National Health Commission &#38; State Administration of Traditional Chinese Medicine"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/CM9.0000000000000819"
                      "Revista" => array:6 [
                        "tituloSerie" => "Chin Med J &#40;Engl&#41;"
                        "fecha" => "2020"
                        "volumen" => "133"
                        "numero" => "9"
                        "paginaInicial" => "1087"
                        "paginaFinal" => "1095"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "SIMIT Societ&#224; Italiana di Malattie Infettive e Tropicali&#46; Linee guida sulla gestione terapeutica e di supporto per pazienti con infezione da coronavirus COVID-19&#46; Edizione 2&#46;0&#44; 12 marzo 2020&#46; &#91;Internet&#93;&#46; Available from&#58; <a target="_blank" href="http://www.simit.org/medias/1569-covid19-vademecum-13-03-202.pdf">http&#58;&#47;&#47;www&#46;simit&#46;org&#47;medias&#47;1569-covid19-vademecum-13-03-202&#46;pdf</a>&#46;"
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tocilizumab&#44; an anti-IL6 receptor antibody&#44; to treat Covid-19-related respiratory failure&#58; a case report"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;-M&#46; Michot"
                            1 => "L&#46; Albiges"
                            2 => "N&#46; Chaput"
                            3 => "V&#46; Saada"
                            4 => "F&#46; Pommeret"
                            5 => "F&#46; Griscelli"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.annonc.2020.03.300"
                      "Revista" => array:3 [
                        "tituloSerie" => "Ann Oncol"
                        "fecha" => "2020"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33736838"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Can we use interleukin-6 &#40;IL-6&#41; blockade for coronavirus disease 2019 &#40;COVID-19&#41;-induced cytokine release syndrome &#40;CRS&#41;&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "B&#46; Liu"
                            1 => "M&#46; Li"
                            2 => "Z&#46; Zhou"
                            3 => "X&#46; Guan"
                            4 => "Y&#46; Xiang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaut.2020.102452"
                      "Revista" => array:2 [
                        "tituloSerie" => "J Autoimmun"
                        "fecha" => "2020"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Characteristics of and important lessons from the coronavirus disease 2019 &#40;COVID-19&#41; outbreak in china&#58; summary of a report of 72314 cases from the Chinese center for disease control and prevention"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "Z&#46; Wu"
                            1 => "J&#46;M&#46; McGoogan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jama.2020.2648"
                      "Revista" => array:6 [
                        "tituloSerie" => "JAMA"
                        "fecha" => "2020"
                        "volumen" => "323"
                        "paginaInicial" => "1239"
                        "paginaFinal" => "1242"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32091533"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Benefit of anakinra in treating pediatric secondary hemophagocytic lymphohistiocytosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46;M&#46; Eloseily"
                            1 => "P&#46; Weiser"
                            2 => "C&#46;B&#46; Crayne"
                            3 => "H&#46; Haines"
                            4 => "M&#46;L&#46; Mannion"
                            5 => "M&#46;L&#46; Stoll"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/art.41103"
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Rheumatol"
                        "fecha" => "2020"
                        "volumen" => "72"
                        "paginaInicial" => "326"
                        "paginaFinal" => "334"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31513353"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Interleukin-1 receptor blockade is associated with reduced mortality in sepsis patients with features of macrophage activation syndrome&#58; reanalysis of a prior phase III trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "B&#46; Shakoory"
                            1 => "J&#46;A&#46; Carcillo"
                            2 => "W&#46;W&#46; Chatham"
                            3 => "R&#46;L&#46; Amdur"
                            4 => "H&#46; Zhao"
                            5 => "C&#46;A&#46; Dinarello"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/CCM.0000000000001402"
                      "Revista" => array:6 [
                        "tituloSerie" => "Crit Care Med"
                        "fecha" => "2016"
                        "volumen" => "44"
                        "paginaInicial" => "275"
                        "paginaFinal" => "281"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26584195"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Therapeutic effect of JAK1&#47;2 blockade on the manifestations of hemophagocytic lymphohistiocytosis in mice"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "S&#46; Maschalidi"
                            1 => "F&#46;E&#46; Sepulveda"
                            2 => "A&#46; Garrigue"
                            3 => "A&#46; Fischer"
                            4 => "G&#46; de Saint Basile"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1182/blood-2016-02-700013"
                      "Revista" => array:6 [
                        "tituloSerie" => "Blood"
                        "fecha" => "2016"
                        "volumen" => "128"
                        "paginaInicial" => "60"
                        "paginaFinal" => "71"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27222478"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "An animal model of hemophagocytic lymphohistiocytosis &#40;HLH&#41;&#58; CD8&#43;T cells and interferon gamma are essential for the disorder"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46;B&#46; Jordan"
                            1 => "D&#46; Hildeman"
                            2 => "J&#46; Kappler"
                            3 => "P&#46; Marrack"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1182/blood-2003-10-3413"
                      "Revista" => array:6 [
                        "tituloSerie" => "Blood"
                        "fecha" => "2004"
                        "volumen" => "104"
                        "paginaInicial" => "735"
                        "paginaFinal" => "743"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15069016"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inhibition of human coronavirus NL63 infection at early stages of the replication cycle"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46; Pyrc"
                            1 => "B&#46;J&#46; Bosch"
                            2 => "B&#46; Berkhout"
                            3 => "M&#46;F&#46; Jebbink"
                            4 => "R&#46; Dijkman"
                            5 => "P&#46; Rottier"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1128/AAC.01598-05"
                      "Revista" => array:6 [
                        "tituloSerie" => "Antimicrob Agents Chemother"
                        "fecha" => "2006"
                        "volumen" => "50"
                        "paginaInicial" => "2000"
                        "paginaFinal" => "2008"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16723558"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Coronavirus associated fulminant myocarditis successfully treated with intravenous immunoglobulin and extracorporeal membrane oxygenation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "S&#46; Rao"
                            1 => "W&#46; Sasser"
                            2 => "F&#46; Diaz"
                            3 => "N&#46; Sharma"
                            4 => "J&#46; Alten"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1378/chest.1992018"
                      "Revista" => array:4 [
                        "tituloSerie" => "Chest &#91;Internet&#93;"
                        "fecha" => "2014"
                        "volumen" => "146"
                        "paginaInicial" => "336A"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "IVIG-mediated protection against necrotizing pneumonia caused by MRSA"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "B&#46;A&#46; Diep"
                            1 => "V&#46;T&#46;M&#46; Le"
                            2 => "C&#46; Badiou"
                            3 => "H&#46;N&#46; Le"
                            4 => "M&#46;G&#46; Pinheiro"
                            5 => "A&#46;H&#46; Duong"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1126/scitranslmed.aaf0746"
                      "Revista" => array:4 [
                        "tituloSerie" => "Sci Transl Med"
                        "fecha" => "2016"
                        "volumen" => "8"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26843188"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Intravenous immunoglobulin exerts reciprocal regulation of Th1&#47;Th17 cells and regulatory T cells in Guillain-Barre syndrome patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;S&#46; Maddur"
                            1 => "M&#46; Rabin"
                            2 => "P&#46; Hegde"
                            3 => "F&#46; Bolgert"
                            4 => "M&#46; Guy"
                            5 => "J&#46;-M&#46; Vallat"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s12026-014-8580-6"
                      "Revista" => array:6 [
                        "tituloSerie" => "Immunol Res"
                        "fecha" => "2014"
                        "volumen" => "60"
                        "paginaInicial" => "320"
                        "paginaFinal" => "329"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25391612"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Intravenous immunoglobulin expands regulatory T cells via induction of cyclooxygenase-2-dependent prostaglandin E2 in human dendritic cells"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Trinath"
                            1 => "P&#46; Hegde"
                            2 => "M&#46; Sharma"
                            3 => "M&#46;S&#46; Maddur"
                            4 => "M&#46; Rabin"
                            5 => "J&#46;-M&#46; Vallat"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1182/blood-2012-11-468264"
                      "Revista" => array:6 [
                        "tituloSerie" => "Blood"
                        "fecha" => "2013"
                        "volumen" => "122"
                        "paginaInicial" => "1419"
                        "paginaFinal" => "1427"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23847198"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Acute respiratory distress syndrome in critically ill patients with severe acute respiratory syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "T&#46;W&#46;K&#46; Lew"
                            1 => "T&#46;-K&#46; Kwek"
                            2 => "D&#46; Tai"
                            3 => "A&#46; Earnest"
                            4 => "S&#46; Loo"
                            5 => "K&#46; Singh"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jama.290.3.374"
                      "Revista" => array:6 [
                        "tituloSerie" => "JAMA"
                        "fecha" => "2003"
                        "volumen" => "290"
                        "paginaInicial" => "374"
                        "paginaFinal" => "380"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12865379"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Deployment of convalescent plasma for the prevention and treatment of COVID-19"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46;M&#46; Bloch"
                            1 => "S&#46; Shoham"
                            2 => "A&#46; Casadevall"
                            3 => "B&#46;S&#46; Sachais"
                            4 => "B&#46; Shaz"
                            5 => "J&#46;L&#46; Winters"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1172/JCI138745"
                      "Revista" => array:3 [
                        "tituloSerie" => "J Clin Invest"
                        "fecha" => "2020"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18431517"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Treatment with novel RSV Ig RI-002 controls viral replication and reduces pulmonary damage in immunocompromised Sigmodon hispidus"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "M&#46; Boukhvalova"
                            1 => "J&#46;C&#46;G&#46; Blanco"
                            2 => "A&#46;R&#46; Falsey"
                            3 => "J&#46; Mond"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/bmt.2015.212"
                      "Revista" => array:6 [
                        "tituloSerie" => "Bone Marrow Transplant"
                        "fecha" => "2016"
                        "volumen" => "51"
                        "paginaInicial" => "119"
                        "paginaFinal" => "126"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26367224"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Xinhua&#46; China puts 245 COVID-19 patients on convalescent plasma therapy &#91;Internet&#93;&#46; Available from&#58; <a target="_blank" href="http://www.xinhuanet.com/english/2020-02/28/c_138828177.htm">http&#58;&#47;&#47;www&#46;xinhuanet&#46;com&#47;english&#47;2020-02&#47;28&#47;c&#95;138828177&#46;htm</a>&#46;"
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The feasibility of convalescent plasma therapy in severe COVID-19 patients&#58; a pilot study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46; Duan"
                            1 => "B&#46; Liu"
                            2 => "C&#46; Li"
                            3 => "H&#46; Zhang"
                            4 => "T&#46; Yu"
                            5 => "J&#46; Qu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:2 [
                      "doi" => "10.1101/2020.03.16.20036145"
                      "Revista" => array:2 [
                        "tituloSerie" => "medRxiv &#91;Internet&#93;"
                        "fecha" => "2020"
                      ]
                    ]
                    1 => array:1 [
                      "WWW" => array:1 [
                        "link" => "http&#58;&#47;&#47;medrxiv&#46;org&#47;content&#47;early&#47;2020&#47;03&#47;23&#47;2020&#46;03&#46;16&#46;20036145&#46;Abstract"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Guidelines on the use of therapeutic apheresis in clinical practice-evidence-based approach from the writing committee of the american society for apheresis&#58; the seventh special issue"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Schwartz"
                            1 => "A&#46; Padmanabhan"
                            2 => "N&#46; Aqui"
                            3 => "R&#46;A&#46; Balogun"
                            4 => "L&#46; Connelly-Smith"
                            5 => "M&#46; Delaney"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/jca.21470"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Apher"
                        "fecha" => "2016"
                        "volumen" => "31"
                        "paginaInicial" => "149"
                        "paginaFinal" => "162"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27322218"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Plasmapheresis in severe sepsis and septic shock&#58; a prospective&#44; randomised&#44; controlled trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "R&#46; Busund"
                            1 => "V&#46; Koukline"
                            2 => "U&#46; Utrobin"
                            3 => "E&#46; Nedashkovsky"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00134-002-1410-7"
                      "Revista" => array:6 [
                        "tituloSerie" => "Intensive Care Med"
                        "fecha" => "2002"
                        "volumen" => "28"
                        "paginaInicial" => "1434"
                        "paginaFinal" => "1439"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12373468"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The efficacy and safety of plasma exchange in patients with sepsis and septic shock&#58; a systematic review and meta-analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46; Rimmer"
                            1 => "B&#46;L&#46; Houston"
                            2 => "A&#46; Kumar"
                            3 => "A&#46;M&#46; Abou-Setta"
                            4 => "C&#46; Friesen"
                            5 => "J&#46;C&#46; Marshall"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s13054-014-0699-2"
                      "Revista" => array:5 [
                        "tituloSerie" => "Crit Care"
                        "fecha" => "2014"
                        "volumen" => "18"
                        "paginaInicial" => "699"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25527094"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib0205"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Use of therapeutic plasma exchange as a rescue therapy in 2009 pH1N1 influenza A&#8212;an associated respiratory failure and hemodynamic shock"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "P&#46; Patel"
                            1 => "V&#46; Nandwani"
                            2 => "J&#46; Vanchiere"
                            3 => "S&#46;A&#46; Conrad"
                            4 => "L&#46;K&#46; Scott"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/PCC.0b013e3181e2a569"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pediatr Crit Care Med"
                        "fecha" => "2011"
                        "volumen" => "12"
                        "paginaInicial" => "e87"
                        "paginaFinal" => "e89"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20453703"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Potential effect of blood purification therapy in reducing cytokine storm as a late complication of critically ill COVID-19"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Ma"
                            1 => "P&#46; Xia"
                            2 => "Y&#46; Zhou"
                            3 => "Z&#46; Liu"
                            4 => "X&#46; Zhou"
                            5 => "J&#46; Wang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Clin Immunol"
                        "fecha" => "2020"
                        "volumen" => "214"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Difference of coagulation features between severe pneumonia induced by SARS-CoV2 and non-SARS-CoV2"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "S&#46; Yin"
                            1 => "M&#46; Huang"
                            2 => "D&#46; Li"
                            3 => "N&#46; Tang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s11239-020-02105-8. r"
                      "Revista" => array:4 [
                        "tituloSerie" => "J Thromb Thrombolysis &#91;Internet&#93;"
                        "fecha" => "2020"
                        "paginaInicial" => "3"
                        "paginaFinal" => "6"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Thrombocytopenia is associated with severe coronavirus disease 2019 &#40;COVID-19&#41; infections&#58; a meta-analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "G&#46; Lippi"
                            1 => "M&#46; Plebani"
                            2 => "B&#46;M&#46; Henry"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cca.2020.03.022"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Chim Acta"
                        "fecha" => "2020"
                        "volumen" => "506"
                        "paginaInicial" => "145"
                        "paginaFinal" => "148"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32178975"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Ferritin in the antiphospholipid syndrome and its catastrophic variant &#40;cAPS&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Agmon-Levin"
                            1 => "C&#46; Rosario"
                            2 => "B&#46;-S&#46;P&#46; Katz"
                            3 => "G&#46; Zandman-Goddard"
                            4 => "P&#46; Meroni"
                            5 => "R&#46; Cervera"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/0961203313504633"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lupus"
                        "fecha" => "2013"
                        "volumen" => "22"
                        "paginaInicial" => "1327"
                        "paginaFinal" => "1335"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24036580"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Coagulopathy and antiphospholipid antibodies in patients with covid-19"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Y&#46; Zhang"
                            1 => "M&#46; Xiao"
                            2 => "S&#46; Zhang"
                            3 => "P&#46; Xia"
                            4 => "W&#46; Cao"
                            5 => "W&#46; Jiang"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMc2007575"
                      "Revista" => array:5 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2020"
                        "volumen" => "382"
                        "paginaInicial" => "e38"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32268022"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "N&#46; Tang"
                            1 => "H&#46; Bai"
                            2 => "X&#46; Chen"
                            3 => "J&#46; Gong"
                            4 => "D&#46; Li"
                            5 => "Z&#46; Sun"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/jth.14817"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Thromb Haemost"
                        "fecha" => "2020"
                        "volumen" => "18"
                        "paginaInicial" => "1094"
                        "paginaFinal" => "1099"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32220112"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib0240"
              "etiqueta" => "48"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "COVID-19 and thrombotic or thromboembolic disease&#58; implications for prevention&#44; antithrombotic therapy&#44; and follow-up &#91;published online ahead of print&#44; 2020 Apr 15&#93;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "B&#46; Bikdeli"
                            1 => "M&#46;V&#46; Madhavan"
                            2 => "D&#46; Jimenez"
                            3 => "T&#46; Chuich"
                            4 => "I&#46; Dreyfus"
                            5 => "E&#46; Driggin"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jacc.2020.04.031"
                      "Revista" => array:3 [
                        "tituloSerie" => "J Am Coll Cardiol"
                        "fecha" => "2020"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27151352"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/21735743/0000001700000008/v1_202110061021/S2173574320301337/v1_202110061021/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "5793"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Special article"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/21735743/0000001700000008/v1_202110061021/S2173574320301337/v1_202110061021/en/main.pdf?idApp=UINPBA00004M&text.app=https://reumatologiaclinica.org/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173574320301337?idApp=UINPBA00004M"
]

Article information

ISSN: 21735743
Original language: English

DOI:10.1016/j.reumae.2020.05.002

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	5	2	7
2024 October	68	25	93
2024 September	92	14	106
2024 August	86	30	116
2024 July	83	42	125
2024 June	97	28	125
2024 May	113	27	140
2024 April	116	36	152
2024 March	116	32	148
2024 February	106	46	152
2024 January	99	44	143
2023 December	111	36	147
2023 November	163	57	220
2023 October	124	29	153
2023 September	239	49	288
2023 August	289	23	312
2023 July	74	24	98
2023 June	63	33	96
2023 May	90	29	119
2023 April	63	16	79
2023 March	93	35	128
2023 February	92	39	131
2023 January	73	43	116
2022 December	160	51	211
2022 November	121	56	177
2022 October	138	46	184
2022 September	103	55	158
2022 August	90	42	132
2022 July	96	62	158
2022 June	102	59	161
2022 May	103	46	149
2022 April	171	68	239
2022 March	63	11	74
2022 February	88	11	99
2022 January	95	15	110
2021 December	191	9	200
2021 November	54	5	59
2021 October	18	6	24
2021 September	64	11	75
2021 August	74	10	84
2021 July	79	10	89
2021 June	107	9	116
2021 May	197	29	226
2021 April	545	48	593
2021 March	297	15	312
2021 February	268	25	293
2021 January	479	54	533
2020 December	338	53	391
2020 November	192	54	246
2020 October	32	12	44

Show all

Indexed in:

Follow us:

Subscribe:

Statistics

Indexed in:

Follow us:

Subscribe:

Statistics

Subscribe to our newsletter