Transcriptome of nasopharyngeal samples from COVID-19 patients and a comparative analysis with other SARS-CoV-2 infection models reveal disparate host responses against SARS-CoV-2

Abstract

Background Although 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. Results Unique 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. Conclusions Even 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.

Acute SARS-CoV-2 infection is associated with an increased abundance of bacterial pathogens, including Pseudomonas aeruginosa in the nose

“…We also profiled the host transcriptional profile of the nasal epithelium in a subset of patients. As recently described (Butler et al, 2021;Islam et al, 2021;Lieberman et al, 2020;Ng et al, 2021), we observed an upregulation of genes associated with innate immune cell activation, antiviral defense, inflammation, and cell death. Furthermore, the upregulation of genes associated with neuronal death and the downregulation of genes influencing epithelial integrity and sensory organ development support a mechanism for infection-induced anosmia and ageusia (de Melo et al, 2021;Melo et al, 2021;Rawson and Huang, 2009).…”

Acute SARS-CoV-2 infection is associated with an expansion of bacteria pathogens in the nose including Pseudomonas Aeruginosa

“…In this study we also profiled the host transcriptional profile of the nasal epithelium in a subset of patients. Our findings highlight an upregulation of genes associated with innate immune cell activation, antiviral defense, and inflammation as recently described (72,73). We also observed a transcriptional signature associated with cell death which has been proposed as a key biosignature of COVID-19 infection (74,75).…”

A BioID-derived proximity interactome for SARS-CoV-2 proteins

“…Not surprisingly, we saw a marked increase in proteins involved in cytokine signaling in immune system (HSA-1280215) in response to viral protein expression, including CD70, IRF9, and TNFSF9. The most significantly upregulated protein we identified was ITGB3 (logFC = +3.32 to +4.78), which has recently been shown to be upregulated in COVID-19 patient lung samples and has been hypothesized to be an alternative receptor for the SARS-CoV-2 virus [26, 27]. We found this ITGB3 upregulation in cells expressing ORF9c, ORF3a, ORF7b, E-protein, and NSP2.…”