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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.

Frontiers in immunology

Authors: Zhaoli Liu, Gizem Kilic, Wenchao Li, Ozlem Bulut, Manoj Kumar Gupta, Bowen Zhang, Cancan Qi, He Peng, Hsin-Chieh Tsay, Chai Fen Soon, Yonatan Ayalew Mekonnen, Anaísa Valido Ferreira, Caspar I van der Made, Bram van Cranenbroek, Hans J P M Koenen, Elles Simonetti, Dimitri Diavatopoulos, Marien I de Jonge, Lisa Müller, Heiner Schaal, Philipp N Ostermann, Markus Cornberg, Britta Eiz-Vesper, Frank van de Veerdonk, Reinout van Crevel, Leo A B Joosten, Jorge Domínguez-Andrés, Cheng-Jian Xu, Mihai G Netea, Yang Li

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.

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.

PMID: 35464396

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