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• W3132103428 abstract "COVID-19 causes severe disease with poor outcomes. We tested the hypothesis that early SARS-CoV-2 viral infection disrupts innate immune responses. These changes may be important for understanding subsequent clinical outcomes. We obtained residual nasopharyngeal swab samples from individuals who requested COVID-19 testing for symptoms at drive-through COVID-19 clinical testing sites operated by the University of Utah. We applied multiplex immunoassays, real-time polymerase chain reaction assays and quantitative proteomics to 20 virus-positive and 20 virus-negative samples. ACE-2 transcripts increased with infection (OR =17.4, 95% CI [CI] =4.78–63.8) and increasing viral N1 protein transcript load (OR =1.16, CI =1.10–1.23). Transcripts for two interferons (IFN) were elevated, IFN-λ1 (OR =71, CI =7.07–713) and IFN-λ2 (OR =40.2, CI =3.86–419), and closely associated with viral N1 transcripts (OR =1.35, CI =1.23–1.49 and OR =1.33 CI =1.20–1.47, respectively). Only transcripts for IP-10 were increased among systemic inflammatory cytokines that we examined (OR =131, CI =1.01–2620). We found widespread discrepancies between transcription and translation. IFN proteins were unchanged or decreased in infected samples (IFN-γ OR =0.90 CI =0.33–0.79, IFN-λ2,3 OR =0.60 CI =0.48–0.74) suggesting viral-induced shut-off of host antiviral protein responses. However, proteins for IP-10 (OR =3.74 CI =2.07–6.77) and several interferon-stimulated genes (ISG) increased with viral load (BST-1 OR =25.1, CI =3.33–188; IFIT1 OR =19.5, CI =4.25–89.2; IFIT3 OR =245, CI =15–4020; MX-1 OR =3.33, CI =1.44–7.70). Older age was associated with substantial modifications of some effects. Ambulatory symptomatic patients had an innate immune response with SARS-CoV-2 infection characterized by elevated IFN, proinflammatory cytokine and ISG transcripts, but there is evidence of a viral-induced host shut-off of antiviral responses. Our findings may characterize the disrupted immune landscape common in patients with early disease." @default.
• W3132103428 created "2021-03-01" @default.
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• W3132103428 date "2021-02-01" @default.
• W3132103428 modified "2023-09-26" @default.
• W3132103428 title "SARS‐CoV‐2 innate effector associations and viral load in early nasopharyngeal infection" @default.
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