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Open Forum Infect Dis . The Longest Persistence of Viable SARS-CoV-2 With Recurrence of Viremia and Relapsing Symptomatic COVID-19 in an Immunocompr

tetano

Editor, Senior Moderator
Open Forum Infect Dis


. 2021 Apr 28;8(11):ofab217.
doi: 10.1093/ofid/ofab217. eCollection 2021 Nov.
The Longest Persistence of Viable SARS-CoV-2 With Recurrence of Viremia and Relapsing Symptomatic COVID-19 in an Immunocompromised Patient-A Case Study


Chiara Sepulcri[SUP] 1 [/SUP], Chiara Dentone[SUP] 2 [/SUP], Malgorzata Mikulska[SUP] 1 2 [/SUP], Bianca Bruzzone[SUP] 3 [/SUP], Alessia Lai[SUP] 4 [/SUP], Daniela Fenoglio[SUP] 5 6 [/SUP], Federica Bozzano[SUP] 2 [/SUP], Annalisa Bergna[SUP] 4 [/SUP], Alessia Parodi[SUP] 6 [/SUP], Tiziana Altosole[SUP] 5 [/SUP], Emanuele Delfino[SUP] 2 [/SUP], Giulia Bartalucci[SUP] 7 [/SUP], Andrea Orsi[SUP] 3 8 [/SUP], Antonio Di Biagio[SUP] 1 2 [/SUP], Gianguglielmo Zehender[SUP] 9 [/SUP], Filippo Ballerini[SUP] 10 [/SUP], Stefano Bonora[SUP] 11 [/SUP], Alessandro Sette[SUP] 12 13 [/SUP], Raffaele De Palma[SUP] 6 14 [/SUP], Guido Silvestri[SUP] 15 16 [/SUP], Andrea De Maria[SUP] 1 2 [/SUP], Matteo Bassetti[SUP] 1 2 [/SUP]



Affiliations

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.

Keywords: SARS-CoV-2; hematological; immunological response; viral shedding; viremia.
 
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