Letter to the Editor
Calcineurin Inhibitors and COVID-19
Inhibidores de la calcineurina y COVID-19
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(B) Complete resolution of the breast edema and healing ACLE rash after four weeks of treatment.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Rashmi Roongta, Samir Joshi, Arghya Chattopadhyay, Alakendu Ghosh" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Rashmi" "apellidos" => "Roongta" ] 1 => array:2 [ "nombre" => "Samir" "apellidos" => "Joshi" ] 2 => array:2 [ "nombre" => "Arghya" "apellidos" => "Chattopadhyay" ] 3 => array:2 [ "nombre" => "Alakendu" "apellidos" => "Ghosh" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1699258X21001522?idApp=UINPBA00004M" "url" => "/1699258X/0000001800000005/v1_202205061004/S1699258X21001522/v1_202205061004/en/main.assets" ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Calcineurin Inhibitors and COVID-19" "tieneTextoCompleto" => true "saludo" => "Dear Editor," "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "314" "paginaFinal" => "315" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "René Hage, Macé M. Schuurmans" "autores" => array:2 [ 0 => array:4 [ "nombre" => "René" "apellidos" => "Hage" "email" => array:1 [ 0 => "rene.hage@usz.ch" ] "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" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Macé M." "apellidos" => "Schuurmans" "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" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "University Hospital Zurich, Division of Pulmonology, Raemistrasse 100, 8091 Zurich, Switzerland" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "University of Zurich, Faculty of Medicine, Raemistrasse 71, 8006 Zurich, Switzerland" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Inhibidores de la calcineurina y COVID-19" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Currently, a disease caused by the Severe Acute Respiratory Coronavirus-2 (SARS CoV-2), named COVID-19, is causing an alarming rate of novel infections, in which Mexico and the South American countries now belong to the most affected countries in the world. SARS CoV-2 is one of the three highly pathogenic coronaviruses being associated with severe, life-threatening disease. Similar to the other dangerous coronaviral infections, namely the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) and the Severe Acute Respiratory Coronavirus (SARS-CoV), there are no clear therapy guidelines.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The authors<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> describe an interesting therapeutic option with cyclosporin A (CsA) as first-line therapy in COVID-19 pneumonia. A definitive treatment for COVID-19 is still not available, and novel therapies (i.e. biologicals) are urgently being investigated.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> Unfortunately evaluating these new therapies takes a lot of time and is very expensive. CsA has been around for decades and could be of special interest due to the large knowledge base.</p><p id="par0015" class="elsevierStylePara elsevierViewall">We certainly agree with the authors that calcineurin inhibitors (CNIs) should be considered in the treatment of COVID-19.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> Both CsA and tacrolimus are commonly prescribed CNIs and widely used for transplant recipients. There are several arguments that suggest a favourable response of CNIs in coronaviral disease.</p><p id="par0020" class="elsevierStylePara elsevierViewall">First of all there are the recent lessons learnt in transplant medicine during the current pandemic of SARS CoV-2: The solid organ transplant recipients showed less severe COVID-19 and thus a better outcome in comparison to the general immunocompetent population.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> Renal-, liver-, heart- and lung transplant recipients are all on long-term immunosuppressive therapy, which generally includes a CNI.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> This kind of immunosuppressive therapy should therefore be considered beneficial rather than labelling it as a risk factor. The lower number of COVID-19 patients among transplant recipients may partially be related to the awareness of their susceptibility to infections since transplantation.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Secondly, the inhibiting effect of CNIs on viral replication of other coronaviruses has been demonstrated in some studies. In vitro studies showed effectiveness of CsA in some coronaviruses.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5,6</span></a> Tacrolimus has been suggested to be effective for disease caused by the MERS-CoV.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> Tacrolimus was also beneficial in animal experiments, showing effective inhibition of viral replication of SARS-CoV.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> For coronaviruses of low pathogenicity tacrolimus showed effective inhibition of viral replication.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8,9</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">The mechanism of coronaviral inhibition could be the protein-protein interactions between SARS-CoV-2 and the human host proteins. These proteins such as the cyclophilin family members and FK506 (tacrolimus)-binding proteins, lead to protection against irreversible cell damage of pneumocytes and T-lymphocytes by SARS CoV-2-induced mitochondrial failure.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">This might prevent the immunological reaction leading to severe hyperinflammation (cytokine storm), which is a feared complication in COVID-19. This systemic overreacting inflammation is characterized by Acute Respiratory Distress Syndrome (ARDS), Systemic Inflammatory Response Syndrome (SIRS) and/or cardiac failure.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Preventing post-COVID-19 lung fibrosis probably cannot be achieved by corticosteroids alone. On the contrary, corticosteroids could lead to prolonged viral shedding and disease progression. In order to inhibit the cytokine storm, CNIs have been suggested to be superior to corticosteroids. The role of other immunosuppressants, such as the antiproliferative agents mycophenolate mofetil (MMF) or azathioprine remains to be determined. However, antiproliferative agents probably are not beneficial in COVID-19, as they diminish the clonal expansion of alloreactive T-cells, and showed high viral loads with more severe or even fatal disease in animal experiments.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Currently, the number of transplant recipients with COVID-19 is limited and therefore only preliminary conclusions concerning CNIs can be made. Even less can be said about CNI treatment for immunocompetent patients with COVID-19.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Therefore we look forward to the results of the Spanish TACROVID trial, in which the role of tacrolimus in the immunocompetent population will be investigated.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Why choose cyclosporin a as first-line therapy in COVID-19 pneumonia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "O. Sanchez-Pernaute" 1 => "F.I. Romero-Bueno" 2 => "A. 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