Multi-Omics Integration Reveals Only Minor Long-Term Molecular and Functional Sequelae in Immune Cells of Individuals Recovered From COVID-19
Liu Z, Kilic G, Li W, Bulut O, Gupta M, Zhang B, Qi C, Peng H, Tsay H, Soon C, Mekonnen Y, Ferreira A, van der Made C, van Cranenbroek B, Koenen H, Simonetti E, Diavatopoulos D, de Jonge M, Müller L, Schaal H, Ostermann P, Cornberg M, Eiz-Vesper B, van de Veerdonk F, van Crevel R, Joosten L, Domínguez-Andrés J, Xu C, Netea M, Li Y
Published in
Frontiers in Immunology: Volume 13, Page 838132
Abstract
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.
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