Alarmin S100A8/A9 mediates activation of aberrant neutrophils in the pathogenesis of COVID-19

To characterize the early immune responses against coronavirus infection, we infected rhesus macaques and hACE2 transgenic mice with SARS-CoV-2 and analyzed the transcriptome of infected and non-infected animals. We infected WT mice with IAV as a normal respiratory virus group. During analysis, we found that S100A8 was dramatically upregulated by SARS-CoV-2 and a mouse coronavirus (mouse hepatitis virus, MHV), but not by other tested viruses. A group of non-canonical neutrophils were also activated during SARS-CoV-2 infection. Overall design: WT Rhesus macaques were infected with SARS-CoV-2 intranasally. Lungs were harvested at 0 dpi, 3 dpi, and 5 dpi. RNA extracted from lungs and RNASeq was performed to identify differentially expressed genes. WT C57BL/6J mice and hACE2 transgenic mice were infected with IAV and MHV intranasally. Lungs were harvested at 0 hour, 6 hour, 24 hour, 48hour, 3day, 5day, 7 day post-infection. RNA extracted from lungs and RNASeq was performed to identify differentially expressed genes. Differentially expressed genes in Lungs of WT Rhesus macaques infected with SARS-CoV-2 and WT mice infected with IAV.