COVID-19 immunopathological features for the prediction and prevention of future emerging respiratory viral infections

<h4>Background & objective</h4>Emerging viral infections can initiate a global pandemic with high mortality. Understanding the immunopathogenesis of these viruses is critical to developing effective strategies for managing/preventing such outbreaks.<h4>Methods</h4>Transcriptomics analysis was performed in a UAE cohort with respective COVID-19 severities. The findings were correlated with published studies of COVID-19 severity/progression GWAS, and transcriptomics data of patients infected with different respiratory viruses.<h4>Results</h4>The transcriptional profiling distinguished significantly between the infected COVID-19 groups and identified the interferon-induced protein, <i>GBP2,</i> as a common significantly up-regulated gene among the different COVID-19 infection severities (nominal <i>p</i> = 0.0019). Key inflammatory pathways were enriched in the higher-severity groups, including Interleukin-1 family signaling. A remarkable immune signature resulted in a trend of cytokine expression changes between all severities, including <i>CCL19, CCL21, IL-19, IL-20, IL-36RN,</i> and members of the IFNA family. The deconvolution of immune cells showed a trend of an uncontrolled pro-inflammatory state and poor immune function in higher disease severities. A systematic analysis of the transcriptomic and GWAS findings identified common signature genes between COVID-19 infection severities including <i>ALCAM, DKK3, EFNA5, FN1, GABRA5, LPAR1, METTL8, MTHFD1L, SPOCK1, TPM4, VTI1A,</i> and <i>WWC2.</i> Differential regulation in potential genes associated with the Interferon signaling pathway including <i>HERC5, IFFI44L, IFI6, RSAD2</i> and <i>SP100</i> was identified as a common feature in transcriptomes of patients afflicted with different virulent respiratory viruses.<h4>Conclusion</h4>Our findings highlight a direction where changes in immune response and specific biomarker panels could be considered as a strategy for the prediction/prevention of new emerging respiratory virus outbreaks.