Glucocorticoids suppress early lung inflammation and impair control of SARS-CoV-2 in non-human primates.

In severe cases of COVID-19, glucocorticoid treatment improves clinical outcomes. However, in non-hospitalized patients, glucocorticoids have limited benefit and may impair viral control. The cell types regulated by glucocorticoids during SARS-CoV-2 infection are currently unknown. Here, we used rhesus macaques to examine the effects of glucocorticoids during the first 14 days of acute SARS-CoV-2 infection. Glucocorticoid treatment decreased local lung inflammation measured with 18FDG-PET/CT imaging. However, glucocorticoid treated animals also had evidence of elevated SARS-CoV-2 viral titers in the lower airways and pulmonary draining lymph nodes. Glucocorticoid treatment blunted plasmacytoid dendritic cell (pDC), eosinophil, innate-like CD8 T cell and early SARS-CoV-2 specific CD8 T cell responses in the airways. These data reveal the cell types that are directly impacted by immunosuppression with glucocorticoids and provide mechanistic insights into the discordant effects of glucocorticoids during SARS-CoV-2 infection. Overall design: Single cell RNA sequencing using 10x genomics 3' kits v3.1 with sample pooling using hashtag barcodes (Biolegend TotalSeqA #1-10). Samples are a time-course (t0, t1, t2, t3, t4) of bronchoalveolar lavage samples from 10 rhesus macaques infected with SARS-CoV-2, with and without glucocorticoid immunosuppression (n=5 of each). Samples from each treatment group were pooled separately for each of the 5 time points. n=5 control animals (hashtags 1-5) n=5 glucocorticoid animals (hashtags 6-10) Pooling resulted in one control and one glucocorticoid sample at each timepoint. We would like help aligning the data, QC, normalizing, scaling, dimensional reduction and perhaps clustering. We have previously used the Seurat pipeline.