This evidence synthesis has been compiled by members of the CITF Secretariat and does not necessarily represent the views of all CITF members.

By Varun Anipindi

In a previous study, Wang et al. demonstrated that COVID-19 disease severity was inversely correlated with T cell-mediated immune responses1. Specifically, recovery from COVID-19 disease was linked to both adequate CD4/CD8 T cell immunity and the level of neutralizing antibodies. This suggests that T cells may play a critical role in resolving COVID-19 infections. Furthermore, data from SARS-CoV-1 infected patients indicate that the longevity of antibody-mediated immune responses is short lived (1 year) while CD8 and CD4 memory T cell responses can persist for over 6-11 years, suggesting a critical role of these T cells in mediating long-term immunity against coronaviruses.

In this new study2 in Nature Communications, the authors wanted to further examine the nature of these memory T cell responses against SARS-CoV-2 by studying T cell responses in a cohort of patients who had recovered from COVID-19, individuals who were in close contact with these patients, and unexposed healthy controls. The authors verified that the majority of COVID-19 recovered individuals developed both CD4 (94%) and CD8 (83%) memory populations against SARS-CoV-2. Surprisingly, while none of the individuals who had close contact to this patient group demonstrated seropositivity to SARS-CoV-2, more than half (54%) developed CD4, and a few (15%) developed CD8 memory T responses against this coronavirus.

This prompted the authors to explore the possibility of pre-existing cross-reactivity against other coronaviruses. They did so by testing samples collected from healthy donors prior to September 2019 and found that only ~3% demonstrated pre-existing cross-reactive CD4 and CD8 memory T cell responses; thus, verifying that the responses observed in the close contact group were specific to SARS-CoV-2. The authors suggest that the lower CD8 T cell responses in this group could be associated with an insufficient viral antigen load, thereby inferring that a productive infection might be needed to mount robust cytotoxic CD8 T cell responses. Additionally, they verified that memory T cell responses were observable in both symptomatic, and to a lesser extent, in asymptomatic patients. Finally, they showed that memory CD4 T cell responses correlated with IgG titers against the RBD and N proteins of the coronavirus.

Overall, this study adds to the complexity of the relationship between humoral- and cell-mediated protection against COVID-19. Remarkably, this is one of the first studies to demonstrate that SARS CoV-2 specific memory T cell responses can be detected in both COVID-19 patients with or without clinical symptoms, as well as their close contacts. Given that current public health efforts focus on monitoring vaccine-mediated protection through antibody responses, this study further highlights the need to undertake a more holistic approach and also monitor T cell immunity to understand the true longevity of immune responses against SARS-CoV-2.


  1. Wang Z, Yang X, Zhou Y, Sun J, Liu X, Zhang J, Mei X, Zhong J, Zhao J, Ran P. COVID-19 Severity Correlates with Weaker T-Cell Immunity, Hypercytokinemia, and Lung Epithelium Injury. Am J Respir Crit Care Med. 2020 Aug 15;202(4):606-610. doi: 10.1164/rccm.202005-1701LE. PMID: 32608999; PMCID: PMC7427397.
  2. Wang Z, Yang X, Zhong J, Zhou Y, Tang Z, Zhou H, He J, Mei X, Tang Y, Lin B, Chen Z, McCluskey J, Yang J, Corbett AJ, Ran P. Exposure to SARS-CoV-2 generates T-cell memory in the absence of a detectable viral infection. Nat Commun. 2021 Mar 19;12(1):1724 doi: 10.1038/s41467-021-22036-z. PMID: 33741972.