Successful use of nirmatrelvir/ritonavir in immunocompromised patients with persistent and/or relapsing COVID-19

In immunocompromised hosts, coronavirus disease 2019 (COVID-19) can span from asymptomatic to severe life-threatening disease. Moreover, chronic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inducing prolonged viral shedding and persistent and/or relapsing symptoms has been reported in these patients.1,2 In chronic SARS-CoV-2 infection, off-label use of remdesivir, convalescent plasma and/or SARS-CoV-2-specific monoclonal antibodies (mAbs) has been anecdotally attempted to reduce disease severity and to achieve viral clearance, with variable results.3,4 Nirmatrelvir/ritonavir is an oral antiviral, which has been proven to reduce by 89% the risk of progression to severe COVID-19 among high-risk patients with early-stage, symptomatic COVID-19.5 Early use of nirmatrelvir/ritonavir has also been shown to shorten time to viral clearance in patients who are immunocompromised and hospitalized with COVID-19.6 To date, there has been limited experience regarding nirmatrelvir/ritonavir efficacy in patients with prolonged and/or relapsing SARS-CoV-2 infection.7 Here we describe three cases of relapsing COVID-19 at the Careggi University Hospital, Florence, Italy, in patients undergoing anti-CD20 immunosuppressant therapy, who showed a successful clinical, virological and radiological response to nirmatrelvir/ritonavir treatment.