ABSTRACT
Antiviral therapies targeting SARS-CoV-2 replication change the course of COVID-19. The European Medicines Agency (EMA) has approved a nirmatrelvir/ritonavir combination that inhibits the main protease of the virus. Molnupiravir, an RNA polymerase misdirector, is proposed by EMA in selected cases, despite still without marketing authorisation. Both are for use in mild disease with a high risk of progression to severe COVID. Patients with inflammatory rheumatic diseases under immunosuppression, mainly high-dose glucocorticoids, are at higher risk of developing severe COVID. We report two clinical cases in which nirmatrelvir/ritonavir and molnupiravir were successfully used to treat COVID-19 in immunosuppressed patients during severe flares of connective tissue diseases, namely systemic lupus erythematosus and dermatomyositis. No significant adverse events attributable to these drugs were noted.