Identification of Distinct Immune Cell Subsets Associated With Asymptomatic Infection, Disease Severity, and Viral Persistence in COVID-19 Patients

Abstract

The cell-mediated protective and pathogenic immune responses to SARS-CoV-2 infection remain largely elusive. Here we identified 76 distinct cell subsets in the PBMC samples that were associated with various clinical presentations of COVID-19 using scRNA-seq technology coupled with a deep and comprehensive analysis of unique cell surface markers and differentially expressed genes. We revealed that (TRAV1-2⁺CD8⁺)MAIT cells and (NCAM1^hiCD160⁺)NK cells significantly enriched in the asymptomatic subjects whereas (LAG3⁺CD160⁺CD8⁺)NKT cells increased in the symptomatic patients. We also observed that (CD68^-CSF1R^-IL1B^hiCD14⁺)classical monocytes were positively correlated with the disease severity. Moreover, (CD33^-HLA-DMA^-CD14⁺)classical monocytes and (CLEC10A^-S100A9^lo)pDC were associated with the viral persistence. The GO and KEGG analyses identified enriched pathways related to immune responses, inflammation, and apoptosis. These findings may enhance our understanding of the immunopathogenesis of COVID-19 and help develop novel strategies against SARS-CoV-2 infection.

Keywords: COVID-19; SARS-CoV-2; asymptomatic infection; disease severity; singlecell RNA sequencing (scRNA-seq); viral persistence.