Does methotrexate influence COVID-19 infection? Case series and mechanistic data

Abstract

Background To investigate whether methotrexate treatment may affect the susceptibility to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods Clinical assessment of symptoms, SARS-CoV-2 RNA, and anti-SARS-CoV-2 IgG in an initial case series of four families and confirmatory case series of seven families, within which one family member developed coronavirus disease 19 (COVID-19) and exposed another family member receiving methotrexate treatment; experimental part with methotrexate treatment of mice and organoids followed by the assessment of mRNA and protein expression of the SARS-CoV-2 receptor angiotensin-converting enzyme (ACE)-2. Results In the initial case series, three of four women on a joint ski trip developed COVID-19, while the fourth woman, under treatment with methotrexate, remained virus-free. Two of the three diseased women infected their husbands, while the third husband treated with methotrexate remained virus-free. In addition, 7 other families were identified in a follow-up case series, in which one member developed COVID-19, while the other, receiving methotrexate, remained healthy. Experimentally, when mice were treated with methotrexate, ACE2 expression significantly decreased in the lung, in the intestinal epithelium, and in intestinal organoids. Conclusion These clinical and experimental data indicate that methotrexate has certain protective effects on SARS-CoV-2 infection via downregulating ACE2.

Influence of biologic and conventional disease-modifying antirheumatic drugs on COVID-19 incidence among rheumatic patients during the first and second wave of the pandemic in Iran

“…Although it is hypothesized that MTX may act protectively against COVID-19 infection due to increased adenosine formation and decreased ACE2 lung receptors [34], our study showed that in higher doses combination DMARDs therapy or disease activity does not support this hypothesis. Moreover, the large number Reumatologia 2022; 60/4 of patients treated with MTX in this study (368 patients) increases the power of our findings.…”

Erythrodermic flare‐up of psoriasis with COVID‐19 infection: A report of two cases and a comprehensive review of literature focusing on the mutual effect of psoriasis and COVID‐19 on each other along with the special challenges of the pandemic

“…A case report has looked into 4 cases that were in close contact and 3 out of 4 of them were infected with COVID‐19 but the fourth one that was under treatment with MTX because of psoriasis did not become infected. 15 Although cyclosporine has been reported to be safer than MTX in the course of COVID‐19 infection but still a number of studies suggest abstain from it. 16 …”

“…13,14 A case report has looked into 4 cases that were in close contact and 3 out of 4 of them were infected with COVID-19 but the fourth one that was under treatment with MTX because of psoriasis did not become infected. 15 Although cyclosporine has been reported to be safer than MTX in the course of COVID-19 infection but still a number of studies suggest abstain from it. 16 Another challenging aspect of this matter is that COVID-19 infection itself provokes immune responses that can be progressed to cytokine storm resulting in a hyperinflammation state in the body that attributes to the pathogenesis of psoriasis, which similarly causes hyperinflammation.…”

Drug repurposing for coronavirus (SARS-CoV-2) based on gene co-expression network analysis

“…Also, Sujoy Khan et al 103 proposed this drug as a potential drug for treating patients infected with COVID-19. Additionally, this drug has a protective effect on SARS-CoV-2 infection via downregulating ACE2 104 . In this study, another drug that we have reported as a potential drug for SARS coronavirus was NICLOSAMIDE .…”