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Immune transcriptome analysis of COVID-19 patients infected with SARS-CoV-2 variants carrying the E484K escape mutation identifies a distinct gene module
Fast-spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) energize the COVID-19 pandemic. While viral infections elicit a conserved immune response, it is not known whether SARS-CoV-2 variants, which display enhanced binding to the ACE2 receptor and reduced neutralizing...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8857234/ https://www.ncbi.nlm.nih.gov/pubmed/35181735 http://dx.doi.org/10.1038/s41598-022-06752-0 |
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author | Lee, Hye Kyung Knabl, Ludwig Knabl, Ludwig Wieser, Manuel Mur, Anna Zabernigg, August Schumacher, Jana Kapferer, Sebastian Kaiser, Norbert Furth, Priscilla A. Hennighausen, Lothar |
author_facet | Lee, Hye Kyung Knabl, Ludwig Knabl, Ludwig Wieser, Manuel Mur, Anna Zabernigg, August Schumacher, Jana Kapferer, Sebastian Kaiser, Norbert Furth, Priscilla A. Hennighausen, Lothar |
author_sort | Lee, Hye Kyung |
collection | PubMed |
description | Fast-spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) energize the COVID-19 pandemic. While viral infections elicit a conserved immune response, it is not known whether SARS-CoV-2 variants, which display enhanced binding to the ACE2 receptor and reduced neutralizing activity by vaccine-elicited antibodies, prompt specific genomic immune responses. To test this, we generated and investigated the transcriptomes in BCs from hospitalized patients infected with either the Alpha variant (n = 36) or with the Alpha variant that had acquired the E484K escape mutation (Alpha+E484K) (n = 13). We identified a gene module preferentially activated in patients infected with the Alpha+E484K variant and in patients infected with the Beta (n = 9) and Gamma (n = 3) variants that also carry by the E484K escape mutation. The E484K signature was enriched for genes preferentially expressed in monocytes and linked to severe viral infection. However, both cohorts had undergone similar treatments and no differences in disease severity were reported suggesting that this signature reflects a variant response and does not necessarily associate with disease outcome. Additionally, longitudinal transcriptome analyses revealed a more persistent retention of immune signatures in Alpha+E484K patients throughout the entire course of COVID-19 disease and convalescence. While the OAS1 Neanderthal mutation has been linked to a milder COVID-19 pathology, we did not identify significant immune transcriptomes differences in the 25 patients homozygous for this mutation. Our study offers insights into distinct molecular immune responses elicited by SARS-CoV-2 variants carrying the E484K escape mutation throughout the COVID-19 disease. |
format | Online Article Text |
id | pubmed-8857234 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-88572342022-02-22 Immune transcriptome analysis of COVID-19 patients infected with SARS-CoV-2 variants carrying the E484K escape mutation identifies a distinct gene module Lee, Hye Kyung Knabl, Ludwig Knabl, Ludwig Wieser, Manuel Mur, Anna Zabernigg, August Schumacher, Jana Kapferer, Sebastian Kaiser, Norbert Furth, Priscilla A. Hennighausen, Lothar Sci Rep Article Fast-spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) energize the COVID-19 pandemic. While viral infections elicit a conserved immune response, it is not known whether SARS-CoV-2 variants, which display enhanced binding to the ACE2 receptor and reduced neutralizing activity by vaccine-elicited antibodies, prompt specific genomic immune responses. To test this, we generated and investigated the transcriptomes in BCs from hospitalized patients infected with either the Alpha variant (n = 36) or with the Alpha variant that had acquired the E484K escape mutation (Alpha+E484K) (n = 13). We identified a gene module preferentially activated in patients infected with the Alpha+E484K variant and in patients infected with the Beta (n = 9) and Gamma (n = 3) variants that also carry by the E484K escape mutation. The E484K signature was enriched for genes preferentially expressed in monocytes and linked to severe viral infection. However, both cohorts had undergone similar treatments and no differences in disease severity were reported suggesting that this signature reflects a variant response and does not necessarily associate with disease outcome. Additionally, longitudinal transcriptome analyses revealed a more persistent retention of immune signatures in Alpha+E484K patients throughout the entire course of COVID-19 disease and convalescence. While the OAS1 Neanderthal mutation has been linked to a milder COVID-19 pathology, we did not identify significant immune transcriptomes differences in the 25 patients homozygous for this mutation. Our study offers insights into distinct molecular immune responses elicited by SARS-CoV-2 variants carrying the E484K escape mutation throughout the COVID-19 disease. Nature Publishing Group UK 2022-02-18 /pmc/articles/PMC8857234/ /pubmed/35181735 http://dx.doi.org/10.1038/s41598-022-06752-0 Text en © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Lee, Hye Kyung Knabl, Ludwig Knabl, Ludwig Wieser, Manuel Mur, Anna Zabernigg, August Schumacher, Jana Kapferer, Sebastian Kaiser, Norbert Furth, Priscilla A. Hennighausen, Lothar Immune transcriptome analysis of COVID-19 patients infected with SARS-CoV-2 variants carrying the E484K escape mutation identifies a distinct gene module |
title | Immune transcriptome analysis of COVID-19 patients infected with SARS-CoV-2 variants carrying the E484K escape mutation identifies a distinct gene module |
title_full | Immune transcriptome analysis of COVID-19 patients infected with SARS-CoV-2 variants carrying the E484K escape mutation identifies a distinct gene module |
title_fullStr | Immune transcriptome analysis of COVID-19 patients infected with SARS-CoV-2 variants carrying the E484K escape mutation identifies a distinct gene module |
title_full_unstemmed | Immune transcriptome analysis of COVID-19 patients infected with SARS-CoV-2 variants carrying the E484K escape mutation identifies a distinct gene module |
title_short | Immune transcriptome analysis of COVID-19 patients infected with SARS-CoV-2 variants carrying the E484K escape mutation identifies a distinct gene module |
title_sort | immune transcriptome analysis of covid-19 patients infected with sars-cov-2 variants carrying the e484k escape mutation identifies a distinct gene module |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8857234/ https://www.ncbi.nlm.nih.gov/pubmed/35181735 http://dx.doi.org/10.1038/s41598-022-06752-0 |
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