OPtimisation of Antiviral Therapy in Immunocompromised COVID-19 Patients

This is a randomized, controlled, factorial, superiority trial to evaluate the viral efficacy of direct antiviral agent nirmatrelvir/r + direct antiviral agent remdesivir versus nirmatrelvir/r alone and of 5 days versus 10 days of nirmatrelvir/r in immunocompromised patients diagnosed with asymptomatic or mild to moderate COVID-19. The primary objective is to assess whether (i) a combination antiviral therapy of two antiviral agents (nirmatrelvir/r + remdesivir and/or (ii) an increase in nirmatrelvir/ r duration from 5 to 10 days improves viral efficacy by decreasing the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV- 2) positivity rate by real time polymerase chain reaction (RT-PCR) (cycle threshold CT\<32) in nasopharyngeal swabs at day 10 (D10). Patients will be eligible if they are immunocompromised, have confirmed asymptomatic SARS-CoV-2 infection or mild to moderate COVID-19, regardless of symptoms onset, provided that they have no contra-indication to any of the study drugs. A total of 256 patients will be recruited in Switzerland and in France, Italy and Norway (through the parallel protocol ANRS0176s OPTICOV). Participants not eligible for randomisation or who refuse to participate to the trial for any reason will be proposed to be included in an exploratory non comparative cohort (maximum 97 participants, active only in Switzerland).