LAUSR

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 1) mild COVID-19, 2) severe COVID-19 before introduction of dexamethasone treatment, and 3) 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 as well as serum neutralizing activity against B.1.1.7, B.1.617.2 in samples ranging from two weeks to six months post 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 to patients without dexamethasone treatment in the early phase of disease, which converged in both groups before six months post infection and also post-immunization. Patients with mild COVID-19 had a comparatively lower T cell and antibody response than patients with severe disease, including a lower response to booster-immunization during convalescence. CONCLUSION Dexamethasone treatment is associated with short-term reduction of T cell and antibody response in severe COVID-19 when compared to the non-treated group, but this difference evens out six months after infection. We confirm higher cellular and humoral immune responses in patients after severe versus mild COVID-19 infection and the concept of improved hybrid immunity upon immunization. TRIAL REGISTRATION n/aFunding: Berlin Institute of Health, German Federal Ministry of Education and German Federal Institute for Drugs and Medical Devices.