Fabian Schälter1,2, Kerstin Dürholz1,2, Laura Bucci1,2, Gerd Burmester3, Roberto Caporali4, Camille Figuereido5,6, Jaime Fogagnolo Cobra5,6, Bernhard Manger1,2, Mario M Zaiss1,2, Georg Schett7,8. 1. Department of Internal Medicine 3, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany. 2. Deutsches Zentrum fuer Immuntherapie (DZI), Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany. 3. Department of Rheumatology and Clinical Immunology, Charité, Berlin, Germany. 4. Department of Clinical Sciences and Community Health, Research Center for Adult and Pediatric Rheumatic Diseases, University of Milan, G. Pini Hospital, Milan, Italy. 5. Cobra Clinic of Rheumatology and Research Center, São Paulo, Brazil. 6. Department of Rheumatology, University of Sao Paulo, São Paulo, Brazil. 7. Department of Internal Medicine 3, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany. georg.schett@uk-erlangen.de. 8. Deutsches Zentrum fuer Immuntherapie (DZI), Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany. georg.schett@uk-erlangen.de.
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.
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 womeninfected 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.