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Multi-Omics Integration Reveals Only Minor Long-Term Molecular and Functional Sequelae in Immune Cells of Individuals Recovered From COVID-19
The majority of COVID-19 patients experience mild to moderate disease course and recover within a few weeks. An increasing number of studies characterized the long-term changes in the specific anti-SARS-CoV-2 immune responses, but how COVID-19 shapes the innate and heterologous adaptive immune syste...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9022455/ https://www.ncbi.nlm.nih.gov/pubmed/35464396 http://dx.doi.org/10.3389/fimmu.2022.838132 |
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author | Liu, Zhaoli Kilic, Gizem Li, Wenchao Bulut, Ozlem Gupta, Manoj Kumar Zhang, Bowen Qi, Cancan Peng, He Tsay, Hsin-Chieh Soon, Chai Fen Mekonnen, Yonatan Ayalew Ferreira, Anaísa Valido van der Made, Caspar I. van Cranenbroek, Bram Koenen, Hans J. P. M. Simonetti, Elles Diavatopoulos, Dimitri de Jonge, Marien I. Müller, Lisa Schaal, Heiner Ostermann, Philipp N. Cornberg, Markus Eiz-Vesper, Britta van de Veerdonk, Frank van Crevel, Reinout Joosten, Leo A. B. Domínguez-Andrés, Jorge Xu, Cheng-Jian Netea, Mihai G. Li, Yang |
author_facet | Liu, Zhaoli Kilic, Gizem Li, Wenchao Bulut, Ozlem Gupta, Manoj Kumar Zhang, Bowen Qi, Cancan Peng, He Tsay, Hsin-Chieh Soon, Chai Fen Mekonnen, Yonatan Ayalew Ferreira, Anaísa Valido van der Made, Caspar I. van Cranenbroek, Bram Koenen, Hans J. P. M. Simonetti, Elles Diavatopoulos, Dimitri de Jonge, Marien I. Müller, Lisa Schaal, Heiner Ostermann, Philipp N. Cornberg, Markus Eiz-Vesper, Britta van de Veerdonk, Frank van Crevel, Reinout Joosten, Leo A. B. Domínguez-Andrés, Jorge Xu, Cheng-Jian Netea, Mihai G. Li, Yang |
author_sort | Liu, Zhaoli |
collection | PubMed |
description | The majority of COVID-19 patients experience mild to moderate disease course and recover within a few weeks. An increasing number of studies characterized the long-term changes in the specific anti-SARS-CoV-2 immune responses, but how COVID-19 shapes the innate and heterologous adaptive immune system after recovery is less well known. To comprehensively investigate the post-SARS-CoV-2 infection sequelae on the immune system, we performed a multi-omics study by integrating single-cell RNA-sequencing, single-cell ATAC-sequencing, genome-wide DNA methylation profiling, and functional validation experiments in 14 convalescent COVID-19 and 15 healthy individuals. We showed that immune responses generally recover without major sequelae after COVID-19. However, subtle differences persist at the transcriptomic level in monocytes, with downregulation of the interferon pathway, while DNA methylation also displays minor changes in convalescent COVID-19 individuals. However, these differences did not affect the cytokine production capacity of PBMCs upon different bacterial, viral, and fungal stimuli, although baseline release of IL-1Ra and IFN-γ was higher in convalescent individuals. In conclusion, we propose that despite minor differences in epigenetic and transcriptional programs, the immune system of convalescent COVID-19 patients largely recovers to the homeostatic level of healthy individuals. |
format | Online Article Text |
id | pubmed-9022455 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90224552022-04-22 Multi-Omics Integration Reveals Only Minor Long-Term Molecular and Functional Sequelae in Immune Cells of Individuals Recovered From COVID-19 Liu, Zhaoli Kilic, Gizem Li, Wenchao Bulut, Ozlem Gupta, Manoj Kumar Zhang, Bowen Qi, Cancan Peng, He Tsay, Hsin-Chieh Soon, Chai Fen Mekonnen, Yonatan Ayalew Ferreira, Anaísa Valido van der Made, Caspar I. van Cranenbroek, Bram Koenen, Hans J. P. M. Simonetti, Elles Diavatopoulos, Dimitri de Jonge, Marien I. Müller, Lisa Schaal, Heiner Ostermann, Philipp N. Cornberg, Markus Eiz-Vesper, Britta van de Veerdonk, Frank van Crevel, Reinout Joosten, Leo A. B. Domínguez-Andrés, Jorge Xu, Cheng-Jian Netea, Mihai G. Li, Yang Front Immunol Immunology The majority of COVID-19 patients experience mild to moderate disease course and recover within a few weeks. An increasing number of studies characterized the long-term changes in the specific anti-SARS-CoV-2 immune responses, but how COVID-19 shapes the innate and heterologous adaptive immune system after recovery is less well known. To comprehensively investigate the post-SARS-CoV-2 infection sequelae on the immune system, we performed a multi-omics study by integrating single-cell RNA-sequencing, single-cell ATAC-sequencing, genome-wide DNA methylation profiling, and functional validation experiments in 14 convalescent COVID-19 and 15 healthy individuals. We showed that immune responses generally recover without major sequelae after COVID-19. However, subtle differences persist at the transcriptomic level in monocytes, with downregulation of the interferon pathway, while DNA methylation also displays minor changes in convalescent COVID-19 individuals. However, these differences did not affect the cytokine production capacity of PBMCs upon different bacterial, viral, and fungal stimuli, although baseline release of IL-1Ra and IFN-γ was higher in convalescent individuals. In conclusion, we propose that despite minor differences in epigenetic and transcriptional programs, the immune system of convalescent COVID-19 patients largely recovers to the homeostatic level of healthy individuals. Frontiers Media S.A. 2022-04-06 /pmc/articles/PMC9022455/ /pubmed/35464396 http://dx.doi.org/10.3389/fimmu.2022.838132 Text en Copyright © 2022 Liu, Kilic, Li, Bulut, Gupta, Zhang, Qi, Peng, Tsay, Soon, Mekonnen, Ferreira, van der Made, van Cranenbroek, Koenen, Simonetti, Diavatopoulos, de Jonge, Müller, Schaal, Ostermann, Cornberg, Eiz-Vesper, van de Veerdonk, van Crevel, Joosten, Domínguez-Andrés, Xu, Netea and Li https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Liu, Zhaoli Kilic, Gizem Li, Wenchao Bulut, Ozlem Gupta, Manoj Kumar Zhang, Bowen Qi, Cancan Peng, He Tsay, Hsin-Chieh Soon, Chai Fen Mekonnen, Yonatan Ayalew Ferreira, Anaísa Valido van der Made, Caspar I. van Cranenbroek, Bram Koenen, Hans J. P. M. Simonetti, Elles Diavatopoulos, Dimitri de Jonge, Marien I. Müller, Lisa Schaal, Heiner Ostermann, Philipp N. Cornberg, Markus Eiz-Vesper, Britta van de Veerdonk, Frank van Crevel, Reinout Joosten, Leo A. B. Domínguez-Andrés, Jorge Xu, Cheng-Jian Netea, Mihai G. Li, Yang Multi-Omics Integration Reveals Only Minor Long-Term Molecular and Functional Sequelae in Immune Cells of Individuals Recovered From COVID-19 |
title | Multi-Omics Integration Reveals Only Minor Long-Term Molecular and Functional Sequelae in Immune Cells of Individuals Recovered From COVID-19 |
title_full | Multi-Omics Integration Reveals Only Minor Long-Term Molecular and Functional Sequelae in Immune Cells of Individuals Recovered From COVID-19 |
title_fullStr | Multi-Omics Integration Reveals Only Minor Long-Term Molecular and Functional Sequelae in Immune Cells of Individuals Recovered From COVID-19 |
title_full_unstemmed | Multi-Omics Integration Reveals Only Minor Long-Term Molecular and Functional Sequelae in Immune Cells of Individuals Recovered From COVID-19 |
title_short | Multi-Omics Integration Reveals Only Minor Long-Term Molecular and Functional Sequelae in Immune Cells of Individuals Recovered From COVID-19 |
title_sort | multi-omics integration reveals only minor long-term molecular and functional sequelae in immune cells of individuals recovered from covid-19 |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9022455/ https://www.ncbi.nlm.nih.gov/pubmed/35464396 http://dx.doi.org/10.3389/fimmu.2022.838132 |
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