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

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.

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.

The transcriptional profiling distinguished significantly between the infected COVID-19 groups and identified the interferon-induced protein, GBP2, as a common significantly up-regulated gene among the different COVID-19 infection severities (nominal p = 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 CCL19, CCL21, IL-19, IL-20, IL-36RN, 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 ALCAM, DKK3, EFNA5, FN1, GABRA5, LPAR1, METTL8, MTHFD1L, SPOCK1, TPM4, VTI1A, and WWC2. Differential regulation in potential genes associated with the Interferon signaling pathway including HERC5, IFFI44L, IFI6, RSAD2 and SP100 was identified as a common feature in transcriptomes of patients afflicted with different virulent respiratory viruses.

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.