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

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



Affiliations

• PMID: 34796242
• PMCID: PMC8135455
• DOI: 10.1093/ofid/ofab217

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.