Open AccessSARS‐CoV‐2 innate effector associations and viral load in early nasopharyngeal infection
Author(s) -
Liou Theodore G.,
Adler Frederick R.,
Cahill Barbara C.,
Cox David R.,
Cox James E.,
Grant Garett J.,
Hanson Kimberly E.,
Hartsell Stephen C.,
Hatton Nathan D.,
Helms My N.,
Jensen Judy L.,
Kartsonaki Christiana,
Li Yanping,
Leung Daniel T.,
Marvin James E.,
Middleton Elizabeth A.,
OsburnStaker Sandra M.,
Packer Kristyn A.,
Shakir Salika M.,
Sturrock Anne B.,
Tardif Keith D.,
Warren Kristi J.,
Waddoups Lindsey J.,
Weaver Lisa J.,
Zimmerman Elizabeth,
Paine Robert
Publication year - 2021
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.14761
Subject(s) - viral load , effector , covid-19 , virology , medicine , innate immune system , immunology , betacoronavirus , virus , disease , infectious disease (medical specialty) , outbreak , immune system
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.