Abstract
The importance of the adaptive T cell response in the control and resolution of viral infection has been well established. However, the nature of T cell–mediated viral control mechanisms in life-threatening stages of COVID-19 has yet to be determined. The aim of the present study was to determine the function and phenotype of T cell populations associated with survival or death of patients with COVID-19 in intensive care as a result of phenotypic and functional profiling by mass cytometry. Increased frequencies of circulating, polyfunctional CD4+CXCR5+HLA-DR+ stem cell memory T cells (Tscms) and decreased proportions of granzyme B–expressing and perforin-expressing effector memory T cells were detected in recovered and deceased patients, respectively. The higher abundance of polyfunctional PD-L1+CXCR3+CD8+ effector T cells (Teffs), CXCR5+HLA-DR+ Tscms, and anti-nucleocapsid (anti-NC) cytokine-producing T cells permitted us to differentiate between recovered and deceased patients. The results from a principal component analysis show an imbalance in the T cell compartment that allowed for the separation of recovered and deceased patients. The paucity of circulating PD-L1+CXCR3+CD8+ Teffs and NC-specific CD8+ T cells accurately forecasts fatal disease outcome. This study provides insight into the nature of the T cell populations involved in the control of COVID-19 and therefore might impact T cell–based vaccine designs for this infectious disease.
Highlights
The emergence of the new SARS-CoV-2–induced coronavirus disease 2019 (COVID-19) outbreak has rapidly emerged as an important healthcare, societal, and economic threat due to its extremely fast worldwide spreading and severity
Fifty-six patients with confirmed SARS-CoV-2 infection were admitted to intensive care unit (ICU) at a median of 9 days after symptoms (Table 1)
Receptor binding domain (RBD), spike subunits 1 (S1) and 2 (S2), and NC-specific IgM, IgG, and IgA were measured in the serum (n = 42)
Summary
The emergence of the new SARS-CoV-2–induced coronavirus disease 2019 (COVID-19) outbreak has rapidly emerged as an important healthcare, societal, and economic threat due to its extremely fast worldwide spreading and severity. Even if the vast majority of cases are asymptomatic or characterized by mild symptoms [1, 2], 6% of patients infected with SARS-CoV-2 suffer from severe symptoms after the development of acute respiratory distress syndrome (ARDS) that can lead to death. Those severe to critical cases have a fatality rate of 2%–8% and require an admission in an intensive care unit We aimed to decipher T cell differentiation and functional profiles during critical SARS-CoV-2 infection in ICUs
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