Abstract
BackgroundAlthough it is becoming evident that individual’s immune system has a decisive influence on SARS-CoV-2 disease progression, pathogenesis is largely unknown. In this study, we aimed to profile the host transcriptome of COVID-19 patients from nasopharyngeal samples along with virus genomic features isolated from respective host, and a comparative analyses of differential host responses in various SARS-CoV-2 infection systems.ResultsUnique and rare missense mutations in 3C-like protease observed in all of our reported isolates. Functional enrichment analyses exhibited that the host induced responses are mediated by innate immunity, interferon, and cytokine stimulation. Surprisingly, induction of apoptosis, phagosome, antigen presentation, hypoxia response was lacking within these patients. Upregulation of immune and cytokine signaling genes such as CCL4, TNFA, IL6, IL1A, CCL2, CXCL2, IFN, and CCR1 were observed in lungs. Lungs lacked the overexpression of ACE2 as suspected, however, high ACE2 but low DPP4 expression was observed in nasopharyngeal cells. Interestingly, directly or indirectly, viral proteins specially non-structural protein mediated overexpression of integrins such as ITGAV, ITGA6, ITGB7, ITGB3, ITGA2B, ITGA5, ITGA6, ITGA9, ITGA4, ITGAE, and ITGA8 in lungs compared to nasopharyngeal samples suggesting the possible way of enhanced invasion. Furthermore, we found comparatively highly expressed transcription factors such as CBP, CEBP, NFAT, ATF3, GATA6, HDAC2, TCF12 which have pivotal roles in lung injury.ConclusionsEven though this study incorporates a limited number of cases, our data will provide valuable insights in developing potential studies to elucidate the differential host responses on the viral pathogenesis in COVID-19, and incorporation of further data will enrich the search of an effective therapeutics.
Highlights
It is becoming evident that individual’s immune system has a decisive influence on SARSCoV-2 disease progression, pathogenesis is largely unknown
Our sequenced SARS‐CoV‐2 isolates showed a divergent variation pattern compared to the other worldwide isolates We sought to find out the genome variations within the four SARS-CoV-2 isolates that we sequenced, and pursued the deviation of these genomes compared to the other isolates from this country
We explored the transcriptome data obtained from the nasopharyngeal samples from COVID-19 patients to find out how these patients were responding against the invading SARS-CoV-2
Summary
It is becoming evident that individual’s immune system has a decisive influence on SARSCoV-2 disease progression, pathogenesis is largely unknown. We aimed to profile the host transcriptome of COVID-19 patients from nasopharyngeal samples along with virus genomic features isolated from respective host, and a comparative analyses of differential host responses in various SARS-CoV-2 infection systems. Since the declaration of COVID-19 pandemic on 11 March, this Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) mediated infection has spread ~ 213 countries and territories [1]. Though the initial fatality was as low as 3.5%, currently this value lies around ~ 6.66% [1] and it might be increased because of the withdrawal of earlier preventing measures taken throughout the world. None of the earlier outbreaks spread as widely as the current ongoing pandemic. More researches on the molecular pathobiology of the COVID-19 are being rapidly carried out to search for effective therapeutic intervention
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