ABSTRACT
PURPOSE OF THE STUDY: T cell lymphopenia is prevalent in severe coronavirus disease 2019 (COVID-19). This study evaluated associations with homeostatic and functional T cell responses in COVID-19 with the goal of identifying immunologic features of severe disease. STUDY POPULATION: Patients aged 18 years and older with symptomatic, real time-quantitative polymerase chain reaction confirmed SARS-CoV-2 (mild, n = 54;severe, n = 49) were recruited at 4 hospitals in the Canton of Zurich, Switzerland from April 2 to August 19, 2020, and a group of healthy controls recruited for comparison (n = 27). A subset (mild, n = 28;severe, n = 38, healthy, n = 22) had comprehensive T cell characterization. METHODS: In this prospective, observational, cross-sectional study, symptomatic participants with mild and severe COVID-19 and healthy controls were sampled at a single time point. Phenotypic and functional characteristics of T cells were evaluated using 40-parameter mass cytometry, flow cytometry, targeted proteomics, and functional assays. RESULTS: Compared with mild disease, severe COVID-19 was associated with T cell lymphopenia and redistribution of T cell populations, including loss of naïve and memory CD4+ and CD8+ T cells, skewing toward CD4+ T follicular helper cells and cytotoxic CD4+ T cells, and expansion of activated and exhausted T cells. Individuals with severe disease and T cell lymphopenia had signs of tissue migration, extensive T cell apoptosis, and impaired T cell responses to common viral antigens. Patients with severe disease also showed elevated interleukin-7 and increased T cell proliferation. Those sampled longest after symptom onset had higher T cell counts and improved antiviral T cell responses. CONCLUSIONS: Severe COVID-19 is characterized by extensive T cell dysfunction. Reduced naïve T cells and virus-specific memory T cell numbers are associated with severe disease and impaired T cell responses to viral antigens, particularly early in the disease. Increased T follicular helper cells may contribute to a robust antibody response often observed in COVID-19. T cell apoptosis is associated with lymphopenia and homeostatic T cell proliferation and T cell recovery in the later stages of disease.