A diagnostic host response biosignature for COVID-19 from RNA profiling of nasal swabs and blood

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease-19 (COVID-19), has emerged as the cause of a global pandemic. We used RNA sequencing to analyze 286 nasopharyngeal (NP) swab and 53 whole-blood (WB) samples from 333 patients with COVID-19 and controls. Overall, a muted immune response was observed in COVID-19 relative to other infections (influenza, other seasonal coronaviruses, and bacterial sepsis), with paradoxical down-regulation of several key differentially expressed genes. Hospitalized patients and outpatients exhibited up-regulation of interferon-associated pathways, although heightened and more robust inflammatory responses were observed in hospitalized patients with more clinically severe illness. Two-layer machine learning–based host classifiers consisting of complete (>1000 genes), medium (<100), and small (<20) gene biomarker panels identified COVID-19 disease with 85.1–86.5% accuracy when benchmarked using an independent test set. SARS-CoV-2 infection has a distinct biosignature that differs between NP swabs and WB and can be leveraged for COVID-19 diagnosis.

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

“…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). Furthermore, the robust upregulation of genes associated with neuronal death and downregulation of genes influencing epithelial integrity and sensory organ development supports a mechanism for infection-induced anosmia and ageusia was not certified by peer review) is the author/funder.…”

Early nasal type I IFN immunity against SARS-CoV-2 is compromised in patients with autoantibodies against type I IFNs

“…We showed that the mucosal IFN-I/III signature was correlated with the blood IFN-I signature. Two recent studies have also reported a strong induction of ISGs in the nasal mucosa of SARS-CoV-2-infected patients, which was even higher compared with patients infected with other viruses, such as influenza or seasonal coronaviruses (Mick et al, 2020;Ng et al, 2021), confirming that a high ISGs expression is a hallmark of anti-SARS-CoV-2 mucosal immunity (Pizzorno et al, 2020). Interestingly, another study has also reported that the nasal ISGs expression was higher in pediatric than in adult patients infected with SARS-CoV-2 (Pierce et al, 2021), which could explain the differences in disease severity observed between these two populations.…”