Evidence map›Paper›PMID 36104754›Full record

Observational studyCritical care (London, England)2022

Plasma SARS-CoV-2 nucleocapsid antigen levels are associated with progression to severe disease in hospitalized COVID-19.

Katherine D Wick, Aleksandra Leligdowicz, Andrew Willmore, Sidney A Carrillo, Rajani Ghale, Alejandra Jauregui, Suzanna S Chak, Viet Nguyen, Deanna Lee, Chayse Jones and 13 more

Open access · goldAbstract readObservational Study
In one paragraph

Observational study in Critical care (London, England), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
3.5field-weighted citation impact, top 6% 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

26 citing papers in PubMed, 36 citations in OpenAlex.

  1. SARS-CoV-2 Plasma Antibody and Nucleocapsid Antigen Status Predict Outcomes in Outpatients With COVID-19.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024
    Trial
  2. Viral and Host Factors Are Associated With Mortality in Hospitalized Patients With COVID-19.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024
    Trial
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors at 6 institutions in 2 countries.

Katherine D WickCardiovascular Research Institute, University of California San Francisco, 503 Parnassus Ave, HSE 760, San Francisco, CA, 94143, USA. kdwick@ucdavis.edu.
Aleksandra LeligdowiczCardiovascular Research Institute, University of California San Francisco, 503 Parnassus Ave, HSE 760, San Francisco, CA, 94143, USA.
Andrew WillmoreDivision of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Sidney A CarrilloDivision of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Rajani GhaleDivision of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Alejandra JaureguiDivision of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Suzanna S ChakDivision of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Viet NguyenCardiovascular Research Institute, University of California San Francisco, 503 Parnassus Ave, HSE 760, San Francisco, CA, 94143, USA.
Deanna LeeCardiovascular Research Institute, University of California San Francisco, 503 Parnassus Ave, HSE 760, San Francisco, CA, 94143, USA.
Chayse JonesDivision of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Robin DewarVirus Isolation and Serology Laboratory, Applied and Developmental Directorate, Frederick National Laboratory, Frederick, MD, USA.
H Clifford LaneDivision of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Kirsten N KangelarisDepartment of Hospital Medicine, University of California San Francisco, San Francisco, CA, USA.
Carolyn M HendricksonDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Zuckerberg San Francisco General Hospital and Trauma Center, University of California San Francisco, San Francisco, USA.
Kathleen D LiuDivision of Nephrology, Department of Medicine, University of California San Francisco School of Medicine, San Francisco, CA, USA.
Pratik SinhaDepartment of Anesthesia, Division of Critical Care, Washington University, St. Louis, MO, USA.
David J ErleCardiovascular Research Institute, University of California San Francisco, 503 Parnassus Ave, HSE 760, San Francisco, CA, 94143, USA.
Charles R LangelierDivision of Infectious Diseases, University of California San Francisco, San Francisco, CA, USA.
Matthew F KrummellImmunoX Initiative, University of California San Francisco, San Francisco, CA, USA.
Prescott G WoodruffCardiovascular Research Institute, University of California San Francisco, 503 Parnassus Ave, HSE 760, San Francisco, CA, 94143, USA.
Carolyn S CalfeeCardiovascular Research Institute, University of California San Francisco, 503 Parnassus Ave, HSE 760, San Francisco, CA, 94143, USA.
Michael A MatthayCardiovascular Research Institute, University of California San Francisco, 503 Parnassus Ave, HSE 760, San Francisco, CA, 94143, USA.
COMET Consortium
University of California, San Francisco · USUniversity of California System · USFrederick National Laboratory for Cancer Research · USNational Institute of Allergy and Infectious Diseases · USSan Francisco General Hospital · USWashington University in St. Louis · US

Funding

Understanding Asthma EndotypesU19AI077439 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PRESCOTT G WOODRUFF · 2008 to 2026
$41.1M
Precision Medicine in the Acute Respiratory Distress SyndromeR35HL140026 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CALFEE, CAROLYN · 2018 to 2024
$6.8M
ADA3: a novel target for HPV16 E6 oncoproteinR01CA094143 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BAND, VIMLA · 2002 to 2006
$1.7M
NCI NIH HHS R01 CA094143NHLBI NIH HHS R35 HL140026NIAID NIH HHS U19 AI077439NIH HHS U19AI077439
6 · The paper itself

Abstract

backgroundStudies quantifying SARS-CoV-2 have focused on upper respiratory tract or plasma viral RNA with inconsistent association with clinical outcomes. The association between plasma viral antigen levels and clinical outcomes has not been previously studied. Our aim was to investigate the relationship between plasma SARS-CoV-2 nucleocapsid antigen (N-antigen) concentration and both markers of host response and clinical outcomes.

methodsSARS-CoV-2 N-antigen concentrations were measured in the first study plasma sample (D0), collected within 72 h of hospital admission, from 256 subjects admitted between March 2020 and August 2021 in a prospective observational cohort of hospitalized patients with COVID-19. The rank correlations between plasma N-antigen and plasma biomarkers of tissue damage, coagulation, and inflammation were assessed. Multiple ordinal regression was used to test the association between enrollment N-antigen plasma concentration and the primary outcome of clinical deterioration at one week as measured by a modified World Health Organization (WHO) ordinal scale. Multiple logistic regression was used to test the association between enrollment plasma N-antigen concentration and the secondary outcomes of ICU admission, mechanical ventilation at 28 days, and death at 28 days. The prognostic discrimination of an externally derived "high antigen" cutoff of N-antigen ≥ 1000 pg/mL was also tested.

resultsN-antigen on D0 was detectable in 84% of study participants. Plasma N-antigen levels significantly correlated with RAGE (r = 0.61), IL-10 (r = 0.59), and IP-10 (r = 0.59, adjusted p = 0.01 for all correlations). For the primary outcome of clinical status at one week, each 500 pg/mL increase in plasma N-antigen level was associated with an adjusted OR of 1.05 (95% CI 1.03-1.08) for worse WHO ordinal status. D0 plasma N-antigen ≥ 1000 pg/mL was 77% sensitive and 59% specific (AUROC 0.68) with a positive predictive value of 23% and a negative predictive value of 93% for a worse WHO ordinal scale at day 7 compared to baseline. D0 N-antigen concentration was independently associated with ICU admission and 28-day mechanical ventilation, but not with death at 28 days.

conclusionsPlasma N-antigen levels are readily measured and provide important insight into the pathogenesis and prognosis of COVID-19. The measurement of N-antigen levels early in-hospital course may improve risk stratification, especially for identifying patients who are unlikely to progress to severe disease.

Indexed as

COVID-19SARS-CoV-2HumansNucleocapsidRNA, ViralRNA, Viral

Identifiers

PMID36104754
PMCPMC9472195
OpenAlexW4295670206

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.