Transcriptomic Similarities and Differences in Host Response between SARS-CoV-2 and Other Viral Infection

COVID-19 is a pandemic that shares only certain clinical characteristics with other acute viral infections. Here, we studied the whole-blood transcriptomic host response to SARS-CoV-2 and compared it with other viral infections to understand similarities and differences in host response. We profiled peripheral blood from 24 healthy controls and 62 prospectively enrolled patients with community-acquired lower respiratory tract infection by SARS-Cov-2 within the first 24 hours of hospital admission using RNA-seq. We also collected 23 independent studies that profiled 1,855 blood samples from patients with one of six viruses (influenza, RSV, HRV, Ebola, Dengue, and SARS). We identified differentially expressed genes that change in patients with COVID-19 or other viral infections. We show changes in gene expression in peripheral blood from patients with COVID-19 are highly correlated with changes in response to other viral infections (r=0.74, p<0.001). However, two genes, ACO1 and ATL3, show significantly different changes in expression. Pathway analysis of differentially expressed genes in patients with COVID-19 or other viral infections versus healthy controls also identified similar pathways including neutrophil activation, innate immune response, immune response to viral infection, and cytokine production for over-expressed genes, as well as lymphocyte differentiation and T cell activation for under-expressed genes. When comparing transcriptome profiles of patients with COVID-19 directly with those with other viral infections, we found 114 and 302 genes were over- and under-expressed, respectively during COVID-19. Pathways analysis did not identify any significant pathways in these genes. Statistical deconvolution using immunoStates found that M1 macrophages, plasmacytoid dendritic cells, CD14+ monocytes, CD4+ T cells, and total B cells showed changes consistently in the same direction across all viral infections including COVID-19. Those that increased in COVID-19 but decreased in non-COVID were CD56bright NK cells, M2 macrophages, and total NK cells. The concordant and discordant responses mapped out via such a comparison provides a window to explore the underlying biology of why COVID-19 is so different from other viral infections encountered so far. Together, results from pathway and immunoStates analyses help dissect major shifts in cellularity and activation of signaling pathways as part of host response to SARS-CoV-2 Total RNA sequencing from whole blood of 62 COVID-19 patients and 24 healthy controls was compared to publicly available expression data from other infections. Please note that raw data is not provided as consent forms do not allow for public access to raw data.