Glucocorticoid-mediated immunosuppression prolongs SARS-CoV-2 replication in the lower airways of rhesus macaques

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B222
Abstract ID: 5107

Presenting Author:
Christine E Nelson , Research Fellow at NIAID, NIH

Abstract:

The mechanisms that regulate the balance between pathogenic inflammation and viral control in the respiratory tract during SARS-CoV-2 are not well-understood. Glucocorticoids have improved clinical outcomes in severe cases of COVID-19, but are not recommended in non-hospitalized patients due to limited efficacy. Here, we used rhesus macaques to examine the effects of glucocorticoids (GC) during acute SARS-CoV-2 infection. Rhesus macaques were pre-treated with intravenous methylprednisolone or saline daily for 5 days and then infected with SARS-CoV-2 delta (B.1.617.2) and animals receiving glucocorticoids were maintained on oral prednisolone. GC treated animals had decreased focal lung inflammation, as detected with ¹⁸FDG-PET/CT imaging, but prolonged viral replication in the lower airways and the pulmonary lymph node. A kinetics of single cell RNA sequencing from the airways revealed prolonged type I IFN responses during GC treatment. GC treated animals had a reduced influx of plasmacytoid dendritic cells (pDC) and eosinophils. Most of the IFNb1 produced in the lung after infection was not made by pDCs but by inflammatory myeloid cells. SARS-CoV-2 specific CD8 T cell responses in the airways were also reduced with GC treatment, as were B cells and T_FH responses in secondary lymphoid organs. Overall, glucocorticoid treatment during SARS-CoV-2 infection reduced lung inflammation, impaired host immune responses, and delayed viral clearance from the lower respiratory tract.