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Authors:Takuya Sekine et al.,  

Journal/Pre-Print:medRxiv 

Tags: Immunology/Immunity, Clinical 

Research Highlights  

  1. Robust memory T cell responses detected months after COVID-19 infection, even in the absence of detectable circulating antibodies specific for SARS-CoV-2, indicating a previously unappreciated heterogeneity of immunity against COVID-19. 

  1. Time to exposure was associated with the emergence of stem-like memory SARS-CoV-2-specific CD8 T cells  

Summary   

The authors characterized cellular and humoral immunity in a cohort of 203 patients with acute moderate or severe COVID-19, convalescent phase after asymptomatic/mild or severe COVID-19, and healthy volunteers from SwedenT cells were shown to display an activated/cycling phenotype, whereas convalescent phase SARS-CoV-2-specific CD8 T cell populations were skewed toward an early differentiated memory phenotype. SARS-CoV-2-specific T cells acquired an early differentiated memory phenotype with higher proliferation and polyfunctionality in the convalescent phase. SARS-CoV-2-specific T cells were also shown to generate anamnestic responses to cognate antigens in the convalescent phase. Memory T cell responses were detected in exposed healthy individuals lacking detectable circulating antibodies, indicating that seroprevalence alone could underestimate population immunity.  

Impact for SARS-CoV2/COVID19 research efforts  

Understand the immune response to SARS-CoV2/COVID19  

Clinical symptoms and pathogenesis of SARS-Cov2/COVID19 

Study Type  

  • In vitro clinical cohort study 

Strengths and limitations of the paper 

Novelty: The study shows that memory T cell responses can be detected in individuals who are exposed or infected with asymptomatic or mild COVID-19 in the absence of humoral responses, suggesting natural exposure or infection could prevent recurrent episodes of severe COVID-19. 

Standing in the field: SARS-Cov2 is known to induce memory T cells responses in individuals with different degrees of infection. The study supporting previous findings (He et al. 2020 and Liu et al 2020) 

Appropriate statistics: Yes but no account taken of multiple (>2) group comparisons 

Viral model used: PBMCs from SARS-CoV-2 infected or -exposed individuals 

Translatability: The study argues in favour of including measurement of virus-specific T cells response as indicator of population immunity 

Main limitation/suggestions:  

  1. The authors conclude that T cell responses in the absence of humoral responses can prevent or limit re-infection. However, minimal evidence was provided in the study of protection and durability of memory T cell responses.  

  1. Further analysis of unsupervised clustering of CD4 and CD8 T cells in different study groups would be helpful to identify un-appreciated T cell phenotype associated with different disease outcomes/stages. Most of the analysis and conclusion in the study was driven by manual gating. 

  1. Comparison of SARS-CoV-2 specific T cells phenotype between acute and convalescent phase included only severe acute phase (with small sample size, n=2). Further analysis of moderate acute and convalescent phase would be helpful to compare phenotype of virus specific T cells within population with similar disease outcomes.  

  1. Healthy volunteers in the study are comprised of two groups: exposed family members, and healthy individuals who donated blood during the pandemic (2020). These individuals were not tested for COVID-19 infection therefore their exposure to the virus is unknown. This is important given that COVID-19 exposure could impact T cell compartment (Grifoni et al, Cell 2020).