Impact of immunosuppression on the immune response to SARS-CoV-2 infection: A mechanistic study

Abstract

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 preincubated 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 =.0137), and IFN-γ (p =.0147) in response to peptide stimulation. There was also a subsequent trend toward a Th2 phenotype, indicated by lower IFN-γ:IL-13 ratio (p =.0663) and IFNγ:IL-4 ratio (p =.0176). Sirolimus appeared to be associated with a proinflammatory cytokine release, including TNF-α (p =.0027) and IL-1β (p =.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.