Abstract

While some individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) present mild-to-severe disease, many SARS-CoV-2-infected individuals are asymptomatic. We sought to identify the distinction of immune response between asymptomatic and moderate patients. We performed single-cell transcriptome and T-cell/B-cell receptor (TCR/BCR) sequencing in 37 longitudinal collected peripheral blood mononuclear cell samples from asymptomatic, moderate, and severe patients with healthy controls. Asymptomatic patients displayed increased CD56briCD16− natural killer (NK) cells and upregulation of interferon-gamma in effector CD4+ and CD8+ T cells and NK cells. They showed more robust TCR clonal expansion, especially in effector CD4+ T cells, but lack strong BCR clonal expansion compared to moderate patients. Moreover, asymptomatic patients have lower interferon-stimulated genes (ISGs) expression in general but large interpatient variability, whereas moderate patients showed various magnitude and temporal dynamics of the ISGs expression across multiple cell populations but lower than a patient with severe disease. Our data provide evidence of different immune signatures to SARS-CoV-2 in asymptomatic infections.

Highlights

  • Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19), has rapidly caused a worldwide pandemic with ever-increasing cases and COVID-19-related deaths.[1]

  • DISCUSSION the immune responses to SARS-CoV-2 infection have been studied in patients with moderate and severe disease,[13,14,15,16,17]

  • The mechanisms under asymptomatic infection of COVID-19 are consistent with our knowledge that these regulatory cells act as less studied

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Summary

1234567890();,: INTRODUCTION

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19), has rapidly caused a worldwide pandemic with ever-increasing cases and COVID-19-related deaths.[1]. The contribution of asymptomatic individuals to the transmission of SARS-CoV-2 raises a significant public health concern.[18] Despite the clinical and immunological assessment of asymptomatic individuals,[19] transcriptome profiles of asymptomatic individuals are lacking, which might help us understand the nature of the asymptomatic COVID-19 disease. To explore characteristics that might lead to immunopathology in asymptomatic and moderate COVID-19, we performed scRNAseq together with single-cell V(D)J sequencing using longitudinal PBMCs from 16 hospitalized COVID-19 patients and three healthy controls (HCs) to identify immunological profiles between distinct immune phenotype and disease severity

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MATERIALS AND METHODS
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