Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Authors:Takuya Sekine et al.,  


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  


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).