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First Author: Xiang-Na Zhao et al 

Journal/preprint name: bioRxiv 

Paper DOI 

Tags:  Immunology/Immunity, Clinical 


Xiang-Na Zhao et al. performed longitudinal single-cell RNA-seq and V(D)J sequencing of PBMCs from 3 healthy donors and 10 COVID-19 patients with asymptomatic, moderate, and severe disease. Severe disease was characterized by an increased type I interferon (IFN-I) responses, diminished T cell clonal expansion, and increased plasma B cells and BCR clonality. In contrast, moderate patients display lower expression of IFN-I related genesrobust T cell clonal expansions, and increased plasma B cells when sampled <10 days after symptom onsetThe asymptomatic condition was found to be an intermediate state between moderate and healthy individuals. Asymptomatic infection was marked by a robust effector CD4+ T cell clonal expansion with upregulated IFNG gene expression. Asymptomatic individuals also showed an increase in CD56briCD16NK cells, with higher expression of cytokines/chemokines (XCL1, XCL2, and IFNG). Furthermore, these individuals display an increased proportion of a Th2-like innate immune subset expressing TNFRSF19 

Research Highlights: 


  1. Asymptomatic individuals lacked clonal expansion of effector CD8+ T cells but had a robust effector CD4+ T cell clonal expansion, coinciding with previously identified SARS-CoV-2-reactive CD4+ T cells in unexposed patients, suggesting pre-existing immunity may contribute to readily armed immunity. 

  1. Asymptomatic patients displayed distinct innate immune responses, including an increased CD56briCD16- NK subset. 

  1. CD56briCD16- NK subset in asymptomatic condition had upregulated cytokine-related genes including IFNG and XCL2. 

  1. Enrichment of less-defined subsets, Th2-like cellexpressing a ciliated cell marker in asymptomatic infection. 

 Impact for COVID-19 research:  

  • Understanding immunological landscape associated with asymptomatic COVID-19 patients and highlight the importance of innate immune response towards disease progression 

  • For clinical setting, the study suggest that distinct NK subsets could be used in diagnosis and therapeutic interventions in COVID-19  


  • Study Typee.g. in vitro analysis   

  • Important cell lines/viral models used: PBMCs from SARS-CoV-2 patients and healthy donors.  

  • Key Techniques:  

  1. Droplet-based single-cell RNA sequencing 

  1. Integrating and clustering techniques for data analysis 


  • As authors pointed, a small sample size: severe patient (n=1), moderate (n=7), and asymptomatic patients (n=2), therefore further investigation with larger cohort is needed to confirm the findings 

  • The analysis was performed in PBMC samples from the patients, it would be interesting to perform such analysis in samples from infected sites (i.e bronchoalveolar lavage (BAL) fluid) to fully dissect to immunological responses associated with asymptomatic in the sites of the infection. 

  • While the authors discussed the differential level of the cytokine-related genes in NK cells between the study groups, limited attention was given to the cytotoxic molecules, including GranzB and perforin, given the recent study linking CD56bright NK cytotoxicity and disease severity (Maucourant et al, 2020).