Abstract

SARS-CoV-2-specific memory T cells will likely prove critical for long-term immune protection against COVID-19. Here, we systematically mapped the functional and phenotypic landscape of SARS-CoV-2-specific T cell responses in unexposed individuals, exposed family members, and individuals with acute or convalescent COVID-19. Acute-phase SARS-CoV-2-specific T cells displayed a highly activated cytotoxic phenotype that correlated with various clinical markers of disease severity, whereas convalescent-phase SARS-CoV-2-specific T cells were polyfunctional and displayed a stem-like memory phenotype. Importantly, SARS-CoV-2-specific T cells were detectable in antibody-seronegative exposed family members and convalescent individuals with a history of asymptomatic and mild COVID-19. Our collective dataset shows that SARS-CoV-2 elicits broadly directed and functionally replete memory T cell responses, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19.

Highlights

  • The world changed in December 2019 with the emergence of a new zoonotic pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes a variety of clinical syndromes collectively termed coronavirus disease 2019 (COVID19)

  • T Cell Perturbations in COVID-19 Our preliminary analyses showed that the absolute numbers and relative frequencies of CD4+ and CD8+ T cells were unphysiologically low in patients with acute moderate or severe COVID-19 (Figures 1A, S1A, and S1B)

  • The following parameters were measured in each sample: viability, C-C chemokine receptor type 7 (CCR7), cluster of differentiation 3 (CD3), CD4, CD8, CD14, CD19, CD25, CD27, CD28, CD38, CD39, CD45RA, CD69, CD95, CD127, cytotoxic

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Summary

Introduction

The world changed in December 2019 with the emergence of a new zoonotic pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes a variety of clinical syndromes collectively termed coronavirus disease 2019 (COVID19). There is no vaccine against SARS-CoV-2, and the excessive inflammation associated with severe COVID-19 can lead to respiratory failure, septic shock, and death (Guan et al, 2020; Wolfel et al, 2020; Wu and McGoogan, 2020). Most people seem to be affected less severely and remain asymptomatic or develop only mild symptoms during COVID-19 (He et al, 2020b; Wei et al, 2020; Yang et al, 2020). It will be critical for public health reasons to determine whether people with milder forms of COVID-19 develop robust immunity against SARS-CoV-2. Recent data have shown that SARS-CoV-2 infection generates near-complete protection against rechallenge in rhesus macaques

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