Short- and long-term T cell and antibody responses following dexamethasone treatment in COVID-19

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Abstract

BACKGROUND After its introduction as standard-of-care for severe COVID-19, dexamethasone has been administered to a large number of patients globally. Detailed knowledge of its impact on the cellular and humoral immune response to SARS-CoV-2 remains scarce.METHODS We included immunocompetent individuals with (a) mild COVID-19, (b) severe COVID-19 before introduction of dexamethasone treatment, and (c) severe COVID-19 infection treated with dexamethasone from prospective observational cohort studies at Charité-Universitätsmedizin Berlin, Germany. We analyzed SARS-CoV-2 spike–reactive T cells, spike-specific IgG titers, and serum neutralizing activity against B.1.1.7 and B.1.617.2 in samples ranging from 2 weeks to 6 months after infection. We also analyzed BA.2 neutralization in sera after booster immunization.RESULTS Patients with severe COVID-19 and dexamethasone treatment had lower T cell and antibody responses to SARS-CoV-2 compared with patients without dexamethasone treatment in the early phase of disease, which converged in both groups before 6 months after infection and also after immunization. Patients with mild COVID-19 had comparatively lower T cell and antibody responses than patients with severe disease, including a lower response to booster immunization during convalescence.CONCLUSION Dexamethasone treatment was associated with a short-term reduction in T cell and antibody responses in severe COVID-19 when compared with the nontreated group, but this difference evened out 6 months after infection. We confirm higher cellular and humoral immune responses in patients after severe versus mild COVID-19 and the concept of improved hybrid immunity upon immunization.FUNDING Berlin Institute of Health, German Federal Ministry of Education, and German Federal Institute for Drugs and Medical Devices.

Authors

Charlotte Thibeault, Lara Bardtke, Kanika Vanshylla, Veronica di Cristanziano, Kirsten A. Eberhardt, Paula Stubbemann, David Hillus, Pinkus Tober-Lau, Parnika Mukherjee, Friederike Münn, Lena J. Lippert, Elisa T. Helbig, Tilman Lingscheid, Fridolin Steinbeis, Mirja Mittermaier, Martin Witzenrath, Thomas Zoller, Pa-COVID study group, Florian Klein, Leif E. Sander, Florian Kurth