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

• Published in: JCI insight Vol. 8; no. 8
• Main Authors: Thibeault, Charlotte, Bardtke, Lara, Vanshylla, Kanika, di Cristanziano, Veronica, Eberhardt, Kirsten A, Stubbemann, Paula, Hillus, David, Tober-Lau, Pinkus, Mukherjee, Parnika, Münn, Friederike, Lippert, Lena J, Helbig, Elisa T, Lingscheid, Tilman, Steinbeis, Fridolin, Mittermaier, Mirja, Witzenrath, Martin, Zoller, Thomas, Klein, Florian, Sander, Leif E, Kurth, Florian
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 24-04-2023; American Society for Clinical investigation
• Subjects: Antibody Formation; Clinical Medicine; COVID-19; COVID-19 Drug Treatment; Dexamethasone - therapeutic use; Humans; Immunization, Secondary; Immunology; Infectious disease; SARS-CoV-2; T-Lymphocytes; Infectious disease; Adaptive immunity; Immunology; T cells; Immunotherapy
• ISSN: 2379-3708; 2379-3708
• DOI: 10.1172/jci.insight.166711

BACKGROUNDAfter 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.METHODSWe 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.RESULTSPatients 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.CONCLUSIONDexamethasone 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.FUNDINGBerlin Institute of Health, German Federal Ministry of Education, and German Federal Institute for Drugs and Medical Devices.