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

Xiaorui Wang,Dong Li,Baojun Zhang,Jingcan Hao,Tingting Jiang,Jiao Xu,Han Bai,Yankui Wang,Mengyang Li,Binghong Zhang,Xianwen Ren,Yuanrui Liu,Qiqi Zeng,Changli Ge,Xin Qi,Chao Fang,Hongyu Qin,Yang Zhao,Bingyin Shi,Chengsheng Zhang,Ke Hu,Junpeng Ma,Xiaobei Chen,Tianlong Huang,Weikang Mao,Fang Hu,Xi Ding

doi:10.3389/fimmu.2022.812514

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 (NCAM1hiCD160+)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-IL1BhiCD14+)classical monocytes were positively correlated with the disease severity. Moreover, (CD33-HLA-DMA-CD14+)classical monocytes and (CLEC10A-S100A9lo)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.

Highlights

The pandemic of COVID-19 has posed unprecedented challenges to the international communities
To identify the immune cell alternations in the peripheral blood of COVID-19 patients with various clinical presentations, we performed the droplet-based scRNA-seq to profile the immune cell landscape in 51 peripheral blood mononuclear cells (PBMCs) samples collected from eleven healthy controls (HC), five asymptomatic individuals (AS), and 33 symptomatic patients (SM) with moderate diseases (MD, n=13) or severe diseases (SD, n=10), and the patients recovered from severe conditions (SD) (SDR, n=10), as well as three samples collected at two different time points during hospitalization from patient C-19 and C-26, respectively (Figure 1A)
We identified a huge number of distinct cell subsets that were associated with asymptomatic infection, disease severity, and viral persistence in COVID-19 patients

Summary

Introduction

The pandemic of COVID-19 has posed unprecedented challenges to the international communities. The clinical presentations of SARS-CoV-2 infection are highly variable, ranging from asymptomatic infections to critical conditions [2,3,4,5,6,7,8,9,10,11,12,13]. One of these reports by a living systematic review of 86 studies in different populations and settings suggested that approximately 20%-31% of SARSCOV-2 infected individuals remained asymptomatic state (AS) during the follow-up period [5]. The immune cells alternations in the LTNP and STNP patients remain largely unknown

Methods

Results

Conclusion