Phenotype and kinetics of SARS-CoV-2–specific T cells in COVID-19 patients with acute respiratory distress syndrome.

Tracking antiviral T cells in COVID-19: In patients infected with SARS-CoV-2, T lymphocytes stimulated by fragments of viral proteins contribute to immunity but may also promote the development of "cytokine storm." Weiskopf et al. studied the emergence of antiviral T cells in the blood of 10 patients with severe COVID-19 requiring ventilator treatment by stimulating blood lymphocytes with pools of peptides based on viral protein sequences. Peptide-reactive CD4⁺ and CD8⁺ T cells were already detectable at ICU admission and generally increased over time. Two of the 10 healthy controls responded weakly to the peptides, suggesting that some T cells induced by common cold coronaviruses can cross-react with SARS-CoV-2 antigens. These foundational studies set the stage for future experiments to tease apart the dynamics of T cell clones specific for different viral antigens. SARS-CoV-2 has been identified as the causative agent of a global outbreak of respiratory tract disease (COVID-19). In some patients, the infection results in moderate to severe acute respiratory distress syndrome, requiring invasive mechanical ventilation. High serum levels of IL-6 and IL-10, and an immune hyperresponsiveness referred to as a "cytokine storm," have been associated with poor clinical outcome. Despite the large numbers of COVID-19 cases and deaths, information on the phenotype and kinetics of SARS-CoV-2–specific T cells is limited. Here, we studied 10 patients with COVID-19 who required admission to an intensive care unit and detected SARS-CoV-2–specific CD4⁺ and CD8⁺ T cells in 10 of 10 and 8 of 10 patients, respectively. We also detected low levels of SARS-CoV-2–reactive T cells in 2 of 10 healthy controls not previously exposed to SARS-CoV-2, which is indicative of cross-reactivity due to past infection with "common cold" coronaviruses. The strongest T cell responses were directed to the spike (S) surface glycoprotein, and SARS-CoV-2–specific T cells predominantly produced effector and T helper 1 (T_H1) cytokines, although T_H2 and T_H17 cytokines were also detected. Furthermore, we studied T cell kinetics and showed that SARS-CoV-2–specific T cells are present relatively early and increase over time. Collectively, these data shed light on the potential variations in T cell responses as a function of disease severity, an issue that is key to understanding the potential role of immunopathology in the disease, and also inform vaccine design and evaluation. [ABSTRACT FROM AUTHOR]