Prior Influenza Infection Mitigates SARS-CoV-2 Disease in Syrian Hamsters.

"data availability statement rna sequencing data were uploaded through geo ( https://www ncbi nlm nih gov/geo/ ; accession number gse254516) and remaining supporting data are given in the supplementary materials . we performed rna sequencing ( supplementary data s1 ) on the nasal epithelium of h1n1 sars-cov-2 and 48 h dual-infected animals focusing on the early post-infection period (days1 and 2) before lung pathology or weight loss became evident.; within the h1n1 group nasal gene expression increased significantly between days1 and 2 post-infection; the overwhelming majority of these genes were upregulated and mapped to pathways involved in innate immunity responses to viral infection apoptosis and activation of the inflammasome ( supplementary data s2 ).; this resulted in 256 largely overexpressed genes enriched for innate immune pathways ( supplementary data s2 and figure 6 ).; these include many genes engaged in innate immune and antiviral pathways ( figure 6 and supplementary data s2 and s3) that are already engaged by the time the host is exposed to sars-cov-2.; when differential gene expression was compared between dual-infected animals and singly sars-cov-2 infected hamsters the vast majority of degs occurred at day 1 (1130 degs) and most of these (917 genes) were relatively underexpressed in dual-infected animals ( supplementary data s3 ).; when comparing deg in both sars-cov-2-infected groups at day 2 (i e 2 days after sars-cov-2-only infection and 4 days after h1n1 infection in the dual-infected group) only five known genes (cd3d ctsw kirrel2 osbpl1a and aurkb) were differentially expressed at padj < 0 05 ( supplementary data s3 ).; supplementary data s1: differential gene expression matrix infection type (n = 3 per time point) compared to control (n = 4).; supplementary data s2: differential gene expression matrix filtered for the following comparisons1 h1n1 (n = 3 day 2) compared to control (n = 4) padj < 0 05 2.; supplementary data s3: 1.; the full list of genes (n = 246 genes) is given in supplementary data s2 . data availability statement rna sequencing data were uploaded through geo ( https://www ncbi nlm nih gov/geo/ ; accession number gse254516"

"Conflicts of Interest The authors declare no conflicts of interest."

"This work was supported by the National Institute of Health-National Institute of Allergy and Infectious Diseases (1R21AI158179-01) through materials and/or salary support for Caroline Zeiss, Brett Lindenbach, Ann Haberman, Peter Smith, Emanuela Bruscia and Antariksh Tyagi. Brent vanderWyk and Heather Allore received salary support from the Claude D. Pepper Older Americans Independence Center from the National Institute of Health-National Institute of Aging (P30AG021342). The Bruker Opterra Swept Field Microscope was funded by shared instrument grant # NIH S10 OD023598. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."