Impact of Immunosuppression on the Immune Response to SARS-CoV-2 Infection: A Mechanistic Study.

Hall, Victoria; Ferreira, Victor; Kumar, Deepali; Humar, Atul

The optimal management of immunosuppression in transplant patients infected with COVID-19 is unknown. We performed an in vitro study to determine the effect of individual immunosuppressive agents on SARS-CoV-2 specific T-cell cytokine expression. Convalescent peripheral blood mononuclear cells from eleven non-immunosuppressed patients with COVID-19 were pre-incubated with clinically relevant concentrations of immunosuppressive drugs (tacrolimus, mycophenolate, sirolimus, prednisone) and then stimulated with a SARS-CoV-2 peptide pool. Supernatants were analyzed by 14-plex high sensitivity T-cell cytokine array. With increasing concentrations of tacrolimus, there was a trend to reduction in the release of IL-2 (p = 0.0137), and IFN-γ (p = 0.0147) in response to peptide stimulation. There was also a subsequent trend towards a Th2 phenotype, indicated by lower IFN- γ:IL-13 ratio (p = 0.0663) and IFNv:IL-4 ratio (p = 0.0176). Sirolimus appeared to be associated with a pro-inflammatory cytokine release, including TNF-α (p = 0.0027) and IL-1β (p = 0.0016), in response to SARS-CoV-2 peptides. In contrast, mycophenolate and prednisone did not influence the SARS-CoV-2-specific cytokine response. These are preliminary findings only, with larger studies required to inform clinical recommendations. This article is protected by copyright. All rights reserved.