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 TITLE=Multi-Omics Integration Reveals Only Minor Long-Term Molecular and Functional Sequelae in Immune Cells of Individuals Recovered From COVID-19 JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.838132 DOI=10.3389/fimmu.2022.838132 ISSN=1664-3224 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.