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Nitesh Kumar Singh, Surabhi Srivastava, Lamuk Zaveri, Thrilok Chander Bingi, Rajarao Mesipogu, Santosh Kumar V, Namami Gaur, Nikhil Hajirnis, Pratheusa Maccha, Sakshi Shambhavi, Shagufta Khan, Mamilla Soujanya, Tulasi Nagabandi, Rakesh K. Mishra, Karthik Bharadwaj Tallapaka, Divya Tej Sowpati

Posted May 15, 2021.

ABSTRACT

Background One of the most perplexing aspects of infection with the SARS-CoV-2 virus has been the variable response elicited in its human hosts. Investigating the transcriptional changes in individuals affected by COVID-19 can help understand and predict the degree of illness and guide clinical outcomes in diverse backgrounds.

Methods Analysis of host transcriptome variations via RNA sequencing from naso/oropharyngeal swabs of COVID-19 patients.

Results We report strong upregulation of the innate immune response, especially type I interferon pathway, upon SARS-CoV-2 infection. Upregulated genes were subjected to a comparative meta-analysis using global datasets to identify a common network of interferon stimulated and viral response genes that mediate the host response and resolution of infection. A large proportion of mis-regulated genes showed a reduction in expression level, suggesting an overall decrease in host mRNA production. Significantly downregulated genes included those encoding olfactory, taste and neuro-sensory receptors. Many pro-inflammatory markers and cytokines were also downregulated or remained unchanged in the COVID-19 patients. Finally, a large number of non-coding RNAs were identified as down-regulated, with a few of the lncRNAs associated with functional roles in directing the response to viral infection.

Conclusions SARS-CoV-2 infection results in the robust activation of the body’s innate immunity. Reduction of gene expression is well correlated with the clinical manifestations and symptoms of COVID-19 such as the loss of smell and taste, and myocardial and neurological complications. This study provides a critical dataset of genes that will enhance our understanding of the nature and prognosis of COVID-19.

Competing Interest Statement

The authors have declared no competing interest.

Paper in collection COVID-19 SARS-CoV-2 preprints from medRxiv and bioRxiv

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