Frontiers in Immunology (Apr 2022)

Multi-Omics Integration Reveals Only Minor Long-Term Molecular and Functional Sequelae in Immune Cells of Individuals Recovered From COVID-19

  • Zhaoli Liu,
  • Zhaoli Liu,
  • Gizem Kilic,
  • Wenchao Li,
  • Wenchao Li,
  • Ozlem Bulut,
  • Manoj Kumar Gupta,
  • Manoj Kumar Gupta,
  • Bowen Zhang,
  • Bowen Zhang,
  • Cancan Qi,
  • Cancan Qi,
  • Cancan Qi,
  • He Peng,
  • He Peng,
  • Hsin-Chieh Tsay,
  • Hsin-Chieh Tsay,
  • Chai Fen Soon,
  • Chai Fen Soon,
  • Yonatan Ayalew Mekonnen,
  • Yonatan Ayalew Mekonnen,
  • Anaísa Valido Ferreira,
  • 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,
  • Markus Cornberg,
  • Markus Cornberg,
  • Britta Eiz-Vesper,
  • Frank van de Veerdonk,
  • Reinout van Crevel,
  • Leo A. B. Joosten,
  • Jorge Domínguez-Andrés,
  • Cheng-Jian Xu,
  • Cheng-Jian Xu,
  • Cheng-Jian Xu,
  • Cheng-Jian Xu,
  • Mihai G. Netea,
  • Mihai G. Netea,
  • Yang Li,
  • Yang Li,
  • Yang Li

DOI
https://doi.org/10.3389/fimmu.2022.838132
Journal volume & issue
Vol. 13

Abstract

Read online

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.

Keywords