Recurrent and persistent fever after SARS-CoV-2 infection in patients with follicular lymphoma: A case series

•Six patients with follicular lymphoma developed recurrent SARS-CoV-2 infection.•Persistent fever is the main symptom, which can last up to 6 months.•SARS-CoV-2 was persistently negative in pharyngeal swabs but positive in bronchoalveolar lavage fluid.•Lymphopenia and B-cell depletion are their common characteristics.•Treatment with nirmatrelvir/ritonavir appeared to be effective in these patients. Although persistent or recurrent COVID-19 infection is well described in some immunosuppressed patient cohort, to date, there have been no reports of this phenomenon in the context of repeatedly negative SARS-CoV-2 testing in the upper respiratory tract. We reported six patients with follicular lymphoma who developed recurrent symptomatic COVID-19 infection. They tested persistently negative for SARS-CoV-2 on pharyngeal swabs and ultimately confirmed by bronchoalveolar lavage fluid metagenomics next-generation sequencing. All six patients presented with lymphopenia and B-cell depletion, and five of them received the anti-cluster of differentiation 20 treatment in the last year. Persistent fever was the most common symptom and bilateral ground-glass opacities were the primary pattern on chest computed tomography. A relatively long course of unnecessary and ineffective antibacterial and/or antifungal treatments was administered until the definitive diagnosis. Persistent fever subsided rapidly with nirmatrelvir/ritonavir treatment. Our case highlighted that recurrent COVID-19 infection should be suspected in immunocompromised patients with persistent fever despite negative pharyngeal swabs, and urgent bronchoalveolar lavage fluid testing is necessary. Treatment with nirmatrelvir/ritonavir appeared to be very effective in these patients.