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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
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135455/ https://www.ncbi.nlm.nih.gov/pubmed/34796242 http://dx.doi.org/10.1093/ofid/ofab217 |
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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 Di Biagio, Antonio Zehender, Gianguglielmo Ballerini, Filippo Bonora, Stefano Sette, Alessandro De Palma, Raffaele Silvestri, Guido De Maria, Andrea Bassetti, Matteo |
author_facet | 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 |
author_sort | Sepulcri, Chiara |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8135455 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-81354552021-05-21 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 Open Forum Infect Dis Major Articles 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. Oxford University Press 2021-04-28 /pmc/articles/PMC8135455/ /pubmed/34796242 http://dx.doi.org/10.1093/ofid/ofab217 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Major Articles 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 The Longest Persistence of Viable SARS-CoV-2 With Recurrence of Viremia and Relapsing Symptomatic COVID-19 in an Immunocompromised Patient—A Case Study |
title | The Longest Persistence of Viable SARS-CoV-2 With Recurrence of Viremia and Relapsing Symptomatic COVID-19 in an Immunocompromised Patient—A Case Study |
title_full | The Longest Persistence of Viable SARS-CoV-2 With Recurrence of Viremia and Relapsing Symptomatic COVID-19 in an Immunocompromised Patient—A Case Study |
title_fullStr | The Longest Persistence of Viable SARS-CoV-2 With Recurrence of Viremia and Relapsing Symptomatic COVID-19 in an Immunocompromised Patient—A Case Study |
title_full_unstemmed | The Longest Persistence of Viable SARS-CoV-2 With Recurrence of Viremia and Relapsing Symptomatic COVID-19 in an Immunocompromised Patient—A Case Study |
title_short | The Longest Persistence of Viable SARS-CoV-2 With Recurrence of Viremia and Relapsing Symptomatic COVID-19 in an Immunocompromised Patient—A Case Study |
title_sort | longest persistence of viable sars-cov-2 with recurrence of viremia and relapsing symptomatic covid-19 in an immunocompromised patient—a case study |
topic | Major Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135455/ https://www.ncbi.nlm.nih.gov/pubmed/34796242 http://dx.doi.org/10.1093/ofid/ofab217 |
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