SARS-CoV-2 innate effector associations and viral load in early nasopharyngeal infection.

Autor: Liou TG; Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA.; Center for Quantitative Biology, University of Utah, Salt Lake City, UT, USA., Adler FR; Center for Quantitative Biology, University of Utah, Salt Lake City, UT, USA.; Department of Mathematics and School of Biological Sciences, University of Utah, Salt Lake City, UT, USA., Cahill BC; Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA., Cox DR; Nuffield College, Oxford, UK., Cox JE; Department of Biochemistry, School of Medicine, University of Utah, Salt Lake City, UT, USA.; Metabolomics, Proteomics and Mass Spectrometry Core, School of Medicine, University of Utah, Salt Lake City, UT, USA., Grant GJ; Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA., Hanson KE; Division of Infectious Diseases, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA.; Department of Pathology, University of Utah, Salt Lake City, UT, USA.; ARUP Laboratories, Salt Lake City, UT, USA., Hartsell SC; Division of Emergency Medicine, Department of Surgery, University of Utah, Salt Lake City, UT, USA., Hatton ND; Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA., Helms MN; Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA., Jensen JL; Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA., Kartsonaki C; Clinical Trial Service Unit & Epidemiological Studies Unit and Medical Research Council Population Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK., Li Y; Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA., Leung DT; Division of Infectious Diseases, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA., Marvin JE; Flow Cytometry Core Laboratory, University of Utah Health, Salt Lake City, UT, USA., Middleton EA; Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA., Osburn-Staker SM; Metabolomics, Proteomics and Mass Spectrometry Core, School of Medicine, University of Utah, Salt Lake City, UT, USA., Packer KA; Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA., Shakir SM; Department of Pathology, University of Utah, Salt Lake City, UT, USA.; ARUP Laboratories, Salt Lake City, UT, USA., Sturrock AB; Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA., Tardif KD; ARUP Laboratories, Salt Lake City, UT, USA., Warren KJ; Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA.; Department of Veterans Affairs Medical Center, Salt Lake City, UT, USA., Waddoups LJ; Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA., Weaver LJ; Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA., Zimmerman E; Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA., Paine R 3rd; Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA.; Department of Veterans Affairs Medical Center, Salt Lake City, UT, USA.
Jazyk: angličtina
Zdroj: Physiological reports [Physiol Rep] 2021 Feb; Vol. 9 (4), pp. e14761.
DOI: 10.14814/phy2.14761
Abstrakt: 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.
(© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)
Databáze: MEDLINE
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