Profound dysregulation of T cell homeostasis and function in patients with severe COVID‐19
Sarah Adamo, Stéphane Chevrier, Carlo Cervia, Yves Zurbuchen, Miro E. Raeber, Liliane Yang, Sujana Sivapatham, Andrea Jacobs, Esther Baechli, Alain Rudiger, Melina Stüssi‐Helbling, Lars C Huber, Dominik J. Schaer, Bernd Bodenmiller, Onur Boyman, Jakob Nilsson
Abstract
Abstract Background Coronavirus disease 2019 (COVID‐19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and shows a broad clinical presentation ranging from asymptomatic infection to fatal disease. A very prominent feature associated with severe COVID‐19 is T cell lymphopenia. However, homeostatic and functional properties of T cells are ill‐defined in COVID‐19. Methods We prospectively enrolled individuals with mild and severe COVID‐19 into our multicenter cohort and performed a cross‐sectional analysis of phenotypic and functional characteristics of T cells using 40‐parameter mass cytometry, flow cytometry, targeted proteomics, and functional assays. Results Compared with mild disease, we observed strong perturbations of peripheral T cell homeostasis and function in severe COVID‐19. Individuals with severe COVID‐19 showed T cell lymphopenia and redistribution of T cell populations, including loss of naïve T cells, skewing toward CD4 + T follicular helper cells and cytotoxic CD4 + T cells, and expansion of activated and exhausted T cells. Extensive T cell apoptosis was particularly evident with severe disease and T cell lymphopenia, which in turn was accompanied by impaired T cell responses to several common viral antigens. Patients with severe disease showed elevated interleukin‐7 and increased T cell proliferation. Furthermore, patients sampled at late time points after symptom onset had higher T cell counts and improved antiviral T cell responses. Conclusion Our study suggests that severe COVID‐19 is characterized by extensive T cell dysfunction and T cell apoptosis, which is associated with signs of homeostatic T cell proliferation and T cell recovery.