Evidence map›Paper›PMID 33625796›Full record

Observational studyPhysiological reports2021

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

Theodore G Liou, Frederick R Adler, Barbara C Cahill, David R Cox, James E Cox, Garett J Grant, Kimberly E Hanson, Stephen C Hartsell, Nathan D Hatton, My N Helms and 16 more

Open access · goldAbstract readObservational Study
In one paragraph

Observational study in Physiological reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.2field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Observational
  11. Article
  12. Article
  13. Review
  14. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors at 3 institutions in 2 countries.

Theodore G LiouDivision of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA.ORCID 0000-0003-0121-4847
Frederick R AdlerCenter for Quantitative Biology, University of Utah, Salt Lake City, UT, USA.ORCID 0000-0002-9022-3157
Barbara C CahillDivision of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA.ORCID 0000-0001-8767-2149
David R CoxNuffield College, Oxford, UK.
James E CoxDepartment of Biochemistry, School of Medicine, University of Utah, Salt Lake City, UT, USA.ORCID 0000-0002-5977-2350
Garett J GrantDivision of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA.ORCID 0000-0002-7266-9964
Kimberly E HansonDivision of Infectious Diseases, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA.ORCID 0000-0001-9790-277X
Stephen C HartsellDivision of Emergency Medicine, Department of Surgery, University of Utah, Salt Lake City, UT, USA.
Nathan D HattonDivision of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA.
My N HelmsDivision of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA.ORCID 0000-0002-0954-8481
Judy L JensenDivision of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA.ORCID 0000-0002-5284-4761
Christiana KartsonakiClinical Trial Service Unit & Epidemiological Studies Unit and Medical Research Council Population Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK.ORCID 0000-0002-3981-3418
Yanping LiDivision of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA.
Daniel T LeungDivision of Infectious Diseases, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA.ORCID 0000-0001-8401-0801
James E MarvinFlow Cytometry Core Laboratory, University of Utah Health, Salt Lake City, UT, USA.
Elizabeth A MiddletonDivision of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA.ORCID 0000-0002-5120-8202
Sandra M Osburn-StakerMetabolomics, Proteomics and Mass Spectrometry Core, School of Medicine, University of Utah, Salt Lake City, UT, USA.
Kristyn A PackerDivision of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA.
Salika M ShakirDepartment of Pathology, University of Utah, Salt Lake City, UT, USA.ORCID 0000-0003-4642-8574
Anne B SturrockDivision of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA.
Keith D TardifARUP Laboratories, Salt Lake City, UT, USA.
Kristi J WarrenDivision of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA.ORCID 0000-0003-0680-4037
Lindsey J WaddoupsDivision of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA.
Lisa J WeaverDivision of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA.
Elizabeth ZimmermanDivision of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA.
Robert PaineDivision of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA.ORCID 0000-0002-4511-4437
University of Utah · USARUP Laboratories (United States) · USUniversity of Oxford · GB

Funding

UTAH REGIONAL CANCER CENTERP30CA042014 · NCI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Jared P Rutter · 1986 to 2026
$72.6M
Utah Center for Clinical and Translational ScienceUL1TR002538 · NCATS · UNIVERSITY OF UTAH · PI HESS, RACHEL, MAJERSIK, JENNIFER JUHL · 2018 to 2022
$26.0M
Proteomics CoreU54DK110858 · NIDDK · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Anna E Beaudin, JAMES Eric COX · 2016 to 2026
$8.6M
Explanatory models of CF Survival, Infection and Intermediate Clinical OutcomesR01HL125520 · NHLBI · UNIVERSITY OF UTAH · PI LIOU, THEODORE GEH-LU · 2015 to 2018
$1.4M
The regulation and function of platelet FcARIIA in sepsisK08HL153953 · NHLBI · UNIVERSITY OF UTAH · PI MIDDLETON, ELIZABETH ANNE · 2020 to 2024
$833k
Q-ToF Mass Spectrometer for the University of Utah MS and Proteomics CoreS10OD018210 · OD · UNIVERSITY OF UTAH · PI COX, JAMES ERIC · 2015 to 2015
$530k
Migration and signaling in ILC2 in asthma: Male and female differencesIK2BX004219 · VA · VA SALT LAKE CITY HEALTHCARE SYSTEM · PI WARREN, KRISTI J · 2020 to 2025
–
Ben B and Iris M Margolis Family Foundation of UtahBLRD VA I01 BX001777BLRD VA IK2 BX004219Claudia Ruth Goodrich Stevens Endowment Fund at the University of UtahNCATS NIH HHS UL1 TR002538NCI NIH HHS 5P30CA042014-24NCI NIH HHS P30 CA042014NHLBI NIH HHS K08 HL153953NHLBI NIH HHS R01 HL125520NIDDK NIH HHS U54 DK110858NIDDK NIH HHS U54DK11085805NIH HHS S10 OD018210NIH HHS S10OD01821001A1
6 · The paper itself

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.

Indexed as

AdolescentAdultAgedAged, 80 and overAge FactorsChildCOVID-19CytokinesEnzyme-Linked Immunosorbent AssayFemaleHumansImmunity, InnateMaleMiddle AgedNasopharyngeal DiseasesReal-Time Polymerase Chain ReactionCytokinesRNA, Messengerbiomarkershost shut-offinnate immunityinterferonSARS-CoV-2

Identifiers

PMID33625796
PMCPMC7903990
OpenAlexW3132103428

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.