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Does methotrexate influence COVID-19 infection? Case series and mechanistic data
Fabian Schälter1,2, Kerstin Dürholz1,2, Laura Bucci1,2
1Department of Internal Medicine 3, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany.
Methotrexate treatment appears to offer protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This drug may reduce susceptibility by downregulating the angiotensin-converting enzyme 2 (ACE2) receptor.
Area of Science:
- Immunology
- Virology
- Pharmacology
Background:
- Investigating the impact of methotrexate on susceptibility to SARS-CoV-2.
- Understanding potential protective mechanisms against COVID-19.
Purpose of the Study:
- To determine if methotrexate treatment influences the risk of SARS-CoV-2 infection.
- To explore the role of ACE2 receptor expression in methotrexate's effect.
Main Methods:
- Case series involving families with COVID-19 exposure.
- Clinical assessment of symptoms, viral RNA, and IgG antibodies.
- Experimental models using mice and organoids treated with methotrexate, assessing ACE2 expression.
Main Results:
- Individuals on methotrexate remained virus-free despite exposure in case series.
- Methotrexate treatment in mice led to decreased ACE2 expression in lungs and intestines.
- ACE2 downregulation observed in mouse organoids treated with methotrexate.
Conclusions:
- Methotrexate demonstrates potential protective effects against SARS-CoV-2 infection.
- The protective mechanism is associated with the downregulation of the ACE2 receptor.
- Further research into methotrexate as a prophylactic or therapeutic agent for COVID-19 is warranted.
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