Short- and long-term T cell and antibody responses following dexamethasone treatment in COVID-19
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
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
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Clinical Research and Public Health Immunology Infectious disease

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

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

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Figure 1

Study flow chart.

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Study flow chart. A total of 208 patients with confirmed SARS-CoV-2 infe...
A total of 208 patients with confirmed SARS-CoV-2 infection and symptom onset between February and December 2020, from prospective observational studies conducted at Charité Universitaetsmedizin Berlin, Germany, were included in this analysis. Sixty-eight were mildly affected and 140 severely affected. Of the severely affected, 64 were treated without and 76 were treated with dexamethasone within standard-of-care according to their date of disease onset. Spike-reactive T cells, RBD IgG titers, and neutralization activity against B.1.1.7 and B.1.6.172 and for postimmunization against BA.2 were measured in blood samples obtained at week 2, month 1, month 3, month 6 after symptom onset, and after single immunization. Numbers of individuals and the proportional overlap with the respective previous time point for each measurement, study visit, and group are shown in the table. N/A, not applicable for the first visit.