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The Longest Persistence of Viable SARS-CoV-2 With Recurrence of Viremia and Relapsing Symptomatic COVID-19 in an Immunocompromised Patient—A Case Study

Abstract Background Immunocompromised patients show prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in nasopharyngeal swabs. We report a case of prolonged persistence of viable SARS-CoV-2 associated with clinical relapses of coronavirus disease 2019 (COVID-19) in a...

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Published in:Open forum infectious diseases 2021-11, Vol.8 (11), p.ofab217-ofab217
Main Authors: 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
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Language:English
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Summary:Abstract Background Immunocompromised patients show prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in nasopharyngeal swabs. We report a case of prolonged persistence of viable SARS-CoV-2 associated with clinical relapses of coronavirus disease 2019 (COVID-19) in a patient with mantle cell lymphoma who underwent treatment with rituximab, bendamustine, cytarabine with consequent lymphopenia and hypogammaglobulinemia. Methods Nasopharyngeal swabs and blood samples were tested for SARS-CoV-2 by real-time polymerase chain reaction (RT-PCR). On 5 positive nasopharyngeal swabs, we performed viral culture and next-generation sequencing. We analyzed the patient’s 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 5 performed viral cultures were positive, and genomic analysis confirmed a persistent infection with the same strain. Viremia resulted positive in 3 out of 4 COVID-19 clinical relapses and cleared each time after remdesivir treatment. The T- and NK-cell 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 >8 months. Viremia was associated with COVID-19 relapses, and remdesivir treatment was effective in viremia clearance and symptom 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; these are probably recruited in inflammatory tissue for viral eradication. In addition, we found a high level of NK-cell repertoire perturbation with relevant involvement during SARS-CoV-2 viremia.
ISSN:2328-8957
2328-8957
DOI:10.1093/ofid/ofab217