Severe type 2 leprosy reaction with COVID-19 with a favourable outcome despite continued use of corticosteroids and methotrexate and a hypothesis on the possible immunological consequences

•Patients with Type 2 leprosy reaction (T2LR) may have a natural protection against severe COVID-19 infection, due to heightened levels of interferon gamma (INF-γ), the main inflammatory mediator in T2LR and a key player in severe acute respiratory syndrome coronavirus 2 clearance.•It is safe to continue methotrexate, for management of severe T2LR in COVID-19 patients.•Methotrexate may be a safe immunosuppressive agent to use in the current scenario owing to non-inhibition of host anti-viral responses. Type 2 leprosy reaction (T2LR), or Erythema Nodosum Leprosum (ENL), often poses a therapeutic challenge to clinicians and commonly requires long courses of steroids for control. While immunosuppressants are known to achieve control and lower steroid dependence in T2LR, the prospect of managing a severe T2LR in conjunction with COVID-19, with the concern of worsening COVID-19 with long-term immunosuppression has not previously been encountered. We report a case of severe T2LR treated with oral steroids and methotrexate, with COVID-19 infection acquired during hospital stay, and a favourable outcome achieved despite the continued use of immunosuppressants. We discuss the possible reasons for this both in terms of the drug pharmacodynamics and the immunological profile of T2LR.