The longest persistence of viable SARS-CoV-2 with recurrence of viremia and relapsing symptomatic COVID-19 in an immunocompromised patient – a case study

Sepulcri, Chiara; Dentone, Chiara; Mikulska, Malgorzata; Bruzzone, Bianca; Lai, Alessia; Fenoglio, Daniela; Bozzano, Federica; Bergna, Annalisa; Parodi, Alessia; Altosole, Tiziana; Delfino, Emanuele; Bartalucci, Giulia; Orsi, Andrea; Di Biagio, Antonio; Zehender, Gianguglielmo; Ballerini, Filippo; Bonora, Stefano; Sette, Alessandro; De Palma, Raffaele; Silvestri, Guido; De Maria, Andrea; Bassetti, Matteo

BACKGROUND: Immunocompromised patients show prolonged shedding of SARS-CoV-2 in nasopharyngeal swabs. We report a case of a prolonged persistence of viable SARS-CoV-2 associated with clinical relapses of COVID-19 in a patient with mantle-cell lymphoma who underwent treatment with R-BAC (rituximab, bendamustine, cytarabine) with consequent lymphopenia and hypogammaglobulinemia. METHODS: Nasopharyngeal swabs and blood samples were tested for SARS-CoV-2 by Real time-PCR (RT-PCR). On five positive nasopharyngeal swabs, we performed viral culture and next generation sequencing. We analysed the patients’ adaptive and innate immunity to characterize T and NK cell subsets. RESULTS: SARS-CoV-2 RT-PCR on nasopharyngeal swabs samples remained positive for 268 days. All five performed viral cultures were positive and genomic analysis confirmed a persistent infection with the same strain. Viremia resulted positive in three out of four COVID-19 clinical relapses and cleared each time after remdesivir treatment. T and NK cells dynamic was different in aviremic and viremic samples and no SARS-CoV-2 specific antibodies were detected throughout the disease course. CONCLUSIONS: In our patient, SARS-CoV-2 persisted with proven infectivity for over eight months. Viremia was associated with COVID-19 relapses and remdesivir treatment was effective in viremia clearance and symptoms remission, although it was unable to clear the virus from the upper respiratory airways. During the viremic phase, we observed a low frequency of terminal effector CD8+ T lymphocytes in peripheral blood that are probably recruited in inflammatory tissue for viral eradication. In addition we found a high level of NK cells repertoire perturbation with a relevant involvement during SARS-CoV-2 viremia.