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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Currently&#44; a disease caused by the Severe Acute Respiratory Coronavirus-2 &#40;SARS CoV-2&#41;&#44; named COVID-19&#44; is causing an alarming rate of novel infections&#44; in which Mexico and the South American countries now belong to the most affected countries in the world&#46; SARS CoV-2 is one of the three highly pathogenic coronaviruses being associated with severe&#44; life-threatening disease&#46; Similar to the other dangerous coronaviral infections&#44; namely the Middle East Respiratory Syndrome Coronavirus &#40;MERS-CoV&#41; and the Severe Acute Respiratory Coronavirus &#40;SARS-CoV&#41;&#44; there are no clear therapy guidelines&#46;</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 &#40;CsA&#41; as first-line therapy in COVID-19 pneumonia&#46; A definitive treatment for COVID-19 is still not available&#44; and novel therapies &#40;i&#46;e&#46; biologicals&#41; are urgently being investigated&#46;<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&#46; CsA has been around for decades and could be of special interest due to the large knowledge base&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">We certainly agree with the authors that calcineurin inhibitors &#40;CNIs&#41; should be considered in the treatment of COVID-19&#46;<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&#46; There are several arguments that suggest a favourable response of CNIs in coronaviral disease&#46;</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&#58; The solid organ transplant recipients showed less severe COVID-19 and thus a better outcome in comparison to the general immunocompetent population&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> Renal-&#44; liver-&#44; heart- and lung transplant recipients are all on long-term immunosuppressive therapy&#44; which generally includes a CNI&#46;<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&#46; The lower number of COVID-19 patients among transplant recipients may partially be related to the awareness of their susceptibility to infections since transplantation&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Secondly&#44; the inhibiting effect of CNIs on viral replication of other coronaviruses has been demonstrated in some studies&#46; In vitro studies showed effectiveness of CsA in some coronaviruses&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5&#44;6</span></a> Tacrolimus has been suggested to be effective for disease caused by the MERS-CoV&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> Tacrolimus was also beneficial in animal experiments&#44; showing effective inhibition of viral replication of SARS-CoV&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> For coronaviruses of low pathogenicity tacrolimus showed effective inhibition of viral replication&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8&#44;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&#46; These proteins such as the cyclophilin family members and FK506 &#40;tacrolimus&#41;-binding proteins&#44; lead to protection against irreversible cell damage of pneumocytes and T-lymphocytes by SARS CoV-2-induced mitochondrial failure&#46;<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 &#40;cytokine storm&#41;&#44; which is a feared complication in COVID-19&#46; This systemic overreacting inflammation is characterized by Acute Respiratory Distress Syndrome &#40;ARDS&#41;&#44; Systemic Inflammatory Response Syndrome &#40;SIRS&#41; and&#47;or cardiac failure&#46;<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&#46; On the contrary&#44; corticosteroids could lead to prolonged viral shedding and disease progression&#46; In order to inhibit the cytokine storm&#44; CNIs have been suggested to be superior to corticosteroids&#46; The role of other immunosuppressants&#44; such as the antiproliferative agents mycophenolate mofetil &#40;MMF&#41; or azathioprine remains to be determined&#46; However&#44; antiproliferative agents probably are not beneficial in COVID-19&#44; as they diminish the clonal expansion of alloreactive T-cells&#44; and showed high viral loads with more severe or even fatal disease in animal experiments&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Currently&#44; the number of transplant recipients with COVID-19 is limited and therefore only preliminary conclusions concerning CNIs can be made&#46; Even less can be said about CNI treatment for immunocompetent patients with COVID-19&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Therefore we look forward to the results of the Spanish TACROVID trial&#44; in which the role of tacrolimus in the immunocompetent population will be investigated&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p></span>"
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Letter to the Editor
Calcineurin Inhibitors and COVID-19
Inhibidores de la calcineurina y COVID-19
René Hagea,b,
Corresponding author
rene.hage@usz.ch

Corresponding author.
, Macé M. Schuurmansa,b
a University Hospital Zurich, Division of Pulmonology, Raemistrasse 100, 8091 Zurich, Switzerland
b University of Zurich, Faculty of Medicine, Raemistrasse 71, 8006 Zurich, Switzerland
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Currently&#44; a disease caused by the Severe Acute Respiratory Coronavirus-2 &#40;SARS CoV-2&#41;&#44; named COVID-19&#44; is causing an alarming rate of novel infections&#44; in which Mexico and the South American countries now belong to the most affected countries in the world&#46; SARS CoV-2 is one of the three highly pathogenic coronaviruses being associated with severe&#44; life-threatening disease&#46; Similar to the other dangerous coronaviral infections&#44; namely the Middle East Respiratory Syndrome Coronavirus &#40;MERS-CoV&#41; and the Severe Acute Respiratory Coronavirus &#40;SARS-CoV&#41;&#44; there are no clear therapy guidelines&#46;</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 &#40;CsA&#41; as first-line therapy in COVID-19 pneumonia&#46; A definitive treatment for COVID-19 is still not available&#44; and novel therapies &#40;i&#46;e&#46; biologicals&#41; are urgently being investigated&#46;<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&#46; CsA has been around for decades and could be of special interest due to the large knowledge base&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">We certainly agree with the authors that calcineurin inhibitors &#40;CNIs&#41; should be considered in the treatment of COVID-19&#46;<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&#46; There are several arguments that suggest a favourable response of CNIs in coronaviral disease&#46;</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&#58; The solid organ transplant recipients showed less severe COVID-19 and thus a better outcome in comparison to the general immunocompetent population&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> Renal-&#44; liver-&#44; heart- and lung transplant recipients are all on long-term immunosuppressive therapy&#44; which generally includes a CNI&#46;<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&#46; The lower number of COVID-19 patients among transplant recipients may partially be related to the awareness of their susceptibility to infections since transplantation&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Secondly&#44; the inhibiting effect of CNIs on viral replication of other coronaviruses has been demonstrated in some studies&#46; In vitro studies showed effectiveness of CsA in some coronaviruses&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">5&#44;6</span></a> Tacrolimus has been suggested to be effective for disease caused by the MERS-CoV&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> Tacrolimus was also beneficial in animal experiments&#44; showing effective inhibition of viral replication of SARS-CoV&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> For coronaviruses of low pathogenicity tacrolimus showed effective inhibition of viral replication&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">8&#44;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&#46; These proteins such as the cyclophilin family members and FK506 &#40;tacrolimus&#41;-binding proteins&#44; lead to protection against irreversible cell damage of pneumocytes and T-lymphocytes by SARS CoV-2-induced mitochondrial failure&#46;<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 &#40;cytokine storm&#41;&#44; which is a feared complication in COVID-19&#46; This systemic overreacting inflammation is characterized by Acute Respiratory Distress Syndrome &#40;ARDS&#41;&#44; Systemic Inflammatory Response Syndrome &#40;SIRS&#41; and&#47;or cardiac failure&#46;<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&#46; On the contrary&#44; corticosteroids could lead to prolonged viral shedding and disease progression&#46; In order to inhibit the cytokine storm&#44; CNIs have been suggested to be superior to corticosteroids&#46; The role of other immunosuppressants&#44; such as the antiproliferative agents mycophenolate mofetil &#40;MMF&#41; or azathioprine remains to be determined&#46; However&#44; antiproliferative agents probably are not beneficial in COVID-19&#44; as they diminish the clonal expansion of alloreactive T-cells&#44; and showed high viral loads with more severe or even fatal disease in animal experiments&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Currently&#44; the number of transplant recipients with COVID-19 is limited and therefore only preliminary conclusions concerning CNIs can be made&#46; Even less can be said about CNI treatment for immunocompetent patients with COVID-19&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">Therefore we look forward to the results of the Spanish TACROVID trial&#44; in which the role of tacrolimus in the immunocompetent population will be investigated&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p></span>"
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Article information
ISSN: 21735743
Original language: English
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Idiomas
Reumatología Clínica (English Edition)
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