학술논문
The Longest Persistence of Viable SARS-CoV-2 With Recurrence of Viremia and Relapsing Symptomatic COVID-19 in an Immunocompromised Patient--A Case Study
MAJOR ARTICLE
MAJOR ARTICLE
Document Type
Case study
Author
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; Biagio, Antonio Di; Zehender, Gianguglielmo; Ballerini, Filippo; Bonora, Stefano; Sette, Alessandro; De Palma, Raffaele; Silvestri, Guido; De Maria, Andrea; Bassetti, Matteo
Source
Open Forum Infectious Diseases. November 2021, Vol. 8 Issue 11
Subject
Language
English
ISSN
2328-8957
Abstract
Persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral shedding and recurrence of positive SARS-CoV-2 nasopharyngeal swabs after a negative sample and symptom remission have been documented both in [...]
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 COVID19 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. hematological, immunological response; SARS-CoV-2; viral shedding; viremia.
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 COVID19 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. hematological, immunological response; SARS-CoV-2; viral shedding; viremia.