In immunocompromised hosts Coronavirus disease 2019 (COVID-19) can range from prolonged asymptomatic viral shedding to persistent/relapsing symptoms. In these conditions off-label use of remdesivir and Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) specific monoclonal antibodies (mAbs) has been endeavored. Nirmatrelvir-ritonavir (NM/r) is an oral antiviral, which has proven to reduce by 89% the risk of progression to severe COVID-19 among high-risk patients with early-stage, symptomatic COVID-19. To date, there are no data about NM/r or mAbs efficacy in patients with prolonged and/or relapsing SARS-CoV-2 infection. 

We describe 5 cases of persistent and/or relapsing COVID-19 in immunocompromised patients observed at the Careggi University Hospital, Florence, Italy successfully treated with oral NM/r or mAbs infusion. 

The clinical characteristics are summarized in Fig.1.

Therapy course of symptoms was collegially discussed. In all cases relapse rather than reinfection was documented by genomic analysis. All patients showed a rapid and full clinical, virological and radiologic response to NM/r or mAbs treatment. 

In our cases, COVID-19 relapse occurred despite initial treatment with remdesivir and/or sotrovimab. At the time of writing, 8 months after NM/r or mABs administration, we have no evidence of further COVID-19 relapse in these patients.