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Authors:Neidleman J et al. 

Journal/ Pre-Print:BioRxiv 

Tags: Bioinformatics, Immunology/Immunity, Proteomics 

Research Highlights

  1. SARS-CoV2 specific CD4+ T-cells present Th1 phenotype, central memory features with helper function and long-lived properties in mild COVID19 successfully recovering patients. 

  1. SARS-CoV2 specific CD8+ T-cells were mostly CD45RA+ with Temra phenotype (comparable to CMV counterparts) but not terminally differentiated (CD27+CD28+). 

  1. SARS-CoV2 specific CD4+ and CD8+ T-cells do not share same phenotype but both have long-lived and homeostatic proliferative subsets. 


In this paper, the authors characterized the phenotype of SARS-CoV2 T-cell responses compared to common CMV T-cell response, in recently recovered patients from mild COVID19 by using CyTOFSARS-CoV2 specific CD4+ T-cells harbor robust Th1 orientated phenotype (mostly Tbethigh and IFN-+ after in vitro stimulation with Spike derived peptidescentral memory phenotype (CD45ROhighCD45RAlowCD27+CCR7int), express significantly ICOS suggesting that they have helper functions, and some CD4+ T-cell present overtime express CD127+ which suggest that they are long-lived. SARS-CoV2 specific CD8+ T-cells display not terminally differentiated Temra features with few capable of homeostatic proliferation (long-lived). 

Impact for SARS-CoV2/COVID19 research efforts 

Understand the immune response to SARS-CoV2/COVID19  

Study Type 

  • bioinformatics study 

  • In vitro study 

  • Clinical Cohort study (from only 4 patients) 

Strengths and limitations of the paper 

Novelty: They focused mainly on memory immune responses in convalescent patients to assess the kind of immunity that remains after COVID19 recovery.  

Appropriate statistics: Almost no statistical analysis – patient number (4) likely too small for meaningful statistical analysis. Mostly descriptive study.  

Viral model used:Four convalescent patients recovering from mild form of COVID19 in San Francisco (USA). In vitro stimulation with Spike-protein, envelope and nucleocapsid derived peptides. 

Translatability:Would require bigger study (greater number of patients) with functional assay to conclude whether having a particular T cell population can protect people (outcome for vaccine efficacy?). 

Main limitations:  

  • Small sample size, 4 patients and 2 uninfected donors. Not age matched.  

  • Data points for SARS-CoV-2-specific T cells are very low, with fewer than 50-90 SARS-CoV-2-specific T cells fro each donor used to make conclusions on phenotype.   

  • Mainly focused on spike-specific T cell responses 

  • Almost no statistical analysis! Mostly descriptive study. 

  • Did not assess functional potential of the cell.  

  • Did not compare to other disease severity recovering patients (severe and critical)