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Different Within-Host Viral Evolution Dynamics in Severely Immunosuppressed Cases with Persistent SARS-CoV-2
A successful Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variant, B.1.1.7, has recently been reported in the UK, causing global alarm. Most likely, the new variant emerged in a persistently infected patient, justifying a special focus on these cases. Our aim in this study was to exp...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301427/ https://www.ncbi.nlm.nih.gov/pubmed/34356872 http://dx.doi.org/10.3390/biomedicines9070808 |
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author | Pérez-Lago, Laura Aldámiz-Echevarría, Teresa García-Martínez, Rita Pérez-Latorre, Leire Herranz, Marta Sola-Campoy, Pedro J. Suárez-González, Julia Martínez-Laperche, Carolina Comas, Iñaki González-Candelas, Fernando Catalán, Pilar Muñoz, Patricia García de Viedma, Darío |
author_facet | Pérez-Lago, Laura Aldámiz-Echevarría, Teresa García-Martínez, Rita Pérez-Latorre, Leire Herranz, Marta Sola-Campoy, Pedro J. Suárez-González, Julia Martínez-Laperche, Carolina Comas, Iñaki González-Candelas, Fernando Catalán, Pilar Muñoz, Patricia García de Viedma, Darío |
author_sort | Pérez-Lago, Laura |
collection | PubMed |
description | A successful Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variant, B.1.1.7, has recently been reported in the UK, causing global alarm. Most likely, the new variant emerged in a persistently infected patient, justifying a special focus on these cases. Our aim in this study was to explore certain clinical profiles involving severe immunosuppression that may help explain the prolonged persistence of viable viruses. We present three severely immunosuppressed cases (A, B, and C) with a history of lymphoma and prolonged SARS-CoV-2 shedding (2, 4, and 6 months), two of whom finally died. Whole-genome sequencing of 9 and 10 specimens from Cases A and B revealed extensive within-patient acquisition of diversity, 12 and 28 new single nucleotide polymorphisms, respectively, which suggests ongoing SARS-CoV-2 replication. This diversity was not observed for Case C after analysing 5 sequential nasopharyngeal specimens and one plasma specimen, and was only observed in one bronchoaspirate specimen, although viral viability was still considered based on constant low Ct values throughout the disease and recovery of the virus in cell cultures. The acquired viral diversity in Cases A and B followed different dynamics. For Case A, new single nucleotide polymorphisms were quickly fixed (13–15 days) after emerging as minority variants, while for Case B, higher diversity was observed at a slower emergence: fixation pace (1–2 months). Slower SARS-CoV-2 evolutionary pace was observed for Case A following the administration of hyperimmune plasma. This work adds knowledge on SARS-CoV-2 prolonged shedding in severely immunocompromised patients and demonstrates viral viability, noteworthy acquired intra-patient diversity, and different SARS-CoV-2 evolutionary dynamics in persistent cases. |
format | Online Article Text |
id | pubmed-8301427 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83014272021-07-24 Different Within-Host Viral Evolution Dynamics in Severely Immunosuppressed Cases with Persistent SARS-CoV-2 Pérez-Lago, Laura Aldámiz-Echevarría, Teresa García-Martínez, Rita Pérez-Latorre, Leire Herranz, Marta Sola-Campoy, Pedro J. Suárez-González, Julia Martínez-Laperche, Carolina Comas, Iñaki González-Candelas, Fernando Catalán, Pilar Muñoz, Patricia García de Viedma, Darío Biomedicines Article A successful Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variant, B.1.1.7, has recently been reported in the UK, causing global alarm. Most likely, the new variant emerged in a persistently infected patient, justifying a special focus on these cases. Our aim in this study was to explore certain clinical profiles involving severe immunosuppression that may help explain the prolonged persistence of viable viruses. We present three severely immunosuppressed cases (A, B, and C) with a history of lymphoma and prolonged SARS-CoV-2 shedding (2, 4, and 6 months), two of whom finally died. Whole-genome sequencing of 9 and 10 specimens from Cases A and B revealed extensive within-patient acquisition of diversity, 12 and 28 new single nucleotide polymorphisms, respectively, which suggests ongoing SARS-CoV-2 replication. This diversity was not observed for Case C after analysing 5 sequential nasopharyngeal specimens and one plasma specimen, and was only observed in one bronchoaspirate specimen, although viral viability was still considered based on constant low Ct values throughout the disease and recovery of the virus in cell cultures. The acquired viral diversity in Cases A and B followed different dynamics. For Case A, new single nucleotide polymorphisms were quickly fixed (13–15 days) after emerging as minority variants, while for Case B, higher diversity was observed at a slower emergence: fixation pace (1–2 months). Slower SARS-CoV-2 evolutionary pace was observed for Case A following the administration of hyperimmune plasma. This work adds knowledge on SARS-CoV-2 prolonged shedding in severely immunocompromised patients and demonstrates viral viability, noteworthy acquired intra-patient diversity, and different SARS-CoV-2 evolutionary dynamics in persistent cases. MDPI 2021-07-13 /pmc/articles/PMC8301427/ /pubmed/34356872 http://dx.doi.org/10.3390/biomedicines9070808 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Pérez-Lago, Laura Aldámiz-Echevarría, Teresa García-Martínez, Rita Pérez-Latorre, Leire Herranz, Marta Sola-Campoy, Pedro J. Suárez-González, Julia Martínez-Laperche, Carolina Comas, Iñaki González-Candelas, Fernando Catalán, Pilar Muñoz, Patricia García de Viedma, Darío Different Within-Host Viral Evolution Dynamics in Severely Immunosuppressed Cases with Persistent SARS-CoV-2 |
title | Different Within-Host Viral Evolution Dynamics in Severely Immunosuppressed Cases with Persistent SARS-CoV-2 |
title_full | Different Within-Host Viral Evolution Dynamics in Severely Immunosuppressed Cases with Persistent SARS-CoV-2 |
title_fullStr | Different Within-Host Viral Evolution Dynamics in Severely Immunosuppressed Cases with Persistent SARS-CoV-2 |
title_full_unstemmed | Different Within-Host Viral Evolution Dynamics in Severely Immunosuppressed Cases with Persistent SARS-CoV-2 |
title_short | Different Within-Host Viral Evolution Dynamics in Severely Immunosuppressed Cases with Persistent SARS-CoV-2 |
title_sort | different within-host viral evolution dynamics in severely immunosuppressed cases with persistent sars-cov-2 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301427/ https://www.ncbi.nlm.nih.gov/pubmed/34356872 http://dx.doi.org/10.3390/biomedicines9070808 |
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