Systems-level profiling of early peripheral host-response landscape variations across COVID-19 severity states in an Indian cohort.

Host immune response to COVID-19 plays a significant role in regulating disease severity. Although big data analysis has provided significant insights into the host biology of COVID-19 across the world, very few such studies have been performed in the Indian population. This study utilizes a transcriptome-integrated network analysis approach to compare the immune responses between asymptomatic or mild and moderate-severe COVID-19 patients in an Indian cohort. An immune suppression phenotype is observed in the early stages of moderate-severe COVID-19 manifestation. A number of pathways are identified that play crucial roles in the host control of the disease such as the type I interferon response and classical complement pathway which show different activity levels across the severity spectrum. This study also identifies two transcription factors, IRF7 and ESR1, to be important in regulating the severity of COVID-19. Overall this study provides a deep understanding of the peripheral immune landscape in the COVID-19 severity spectrum in the Indian genetic background and opens up future research avenues to compare immune responses across global populations.