Persistent SARS-CoV-2 infection: the aftermath of the pandemic.

<bold>Introduction:</bold> Imunocompromised patients, especially those with B-cell depleting disease or therapy, face an elevated risk of persistent SARS-CoV-2 infection, often underdiagnosed, with limited data on its management. <bold>Methods:</bold> A retrospective observational study from September 2021 to October 2023 of patients with persistent SARS-CoV-2 infection. Persistent infection was defined by symptoms (>21 days from initial positive test), consistent imaging and persistent or intermittent positive RT-PCR >21 days based on an applied algorithm. Epidemiological and clinical characteristics, hospitalizations, therapeutic regimens and outcome were recorded. <bold>Results:</bold> 19 patients (58% male) with median age 63 [IQR 54-78] years. 12 (63%) had hematological malignancy (3 CLL, 9 NHL), 15 (79%) received anti-CD20 treatment (last 8 months, 12 rituximab) and 9 (47%) both. Median duration of symptoms 62 [46-137] days. 2 (10%) were paucisymptomatic, 11 (58%) had recurrent and 6 (32%) progressive symptoms with severe respiratory failure (3 HFNC/3 IMV). 5 (26%) diagnosed by bronchoscopy (BAL). 15 (79%) required >1 and 8 (42%) >2 hospitalizations. Regarding eradication trials, 13 (68%) received multiple regimens of remdesivir with or without immunomodulators, 6 (32%) dual antiviral therapy (remdesivir and nirmatrevil/ritonavir) and 9 (47%) intravenous immunoglobulin (5 documented hypogammaglobulimemia). 2 (10%) deceased within the first 3 months after diagnosis (IMV) and 2 (10%) within 1 year (multiple hospitalizations). <bold>Conclusion:</bold> Persistent SARS-CoV-2 infection increases morbidity and probably mortality, posing a major public health issue. However, randomized trials are crucial to determine the optimal diagnostic and therapeutic approach.