Evidence map›Paper›PMID 34383886›Full record

ArticleClinical chemistry2021

Femtomolar SARS-CoV-2 Antigen Detection Using the Microbubbling Digital Assay with Smartphone Readout Enables Antigen Burden Quantitation and Tracking.

Hui Chen, Zhao Li, Sheng Feng, Melissa Richard-Greenblatt, Emily Hutson, Stefen Andrianus, Laurel J Glaser, Kyle G Rodino, Jianing Qian, Dinesh Jayaraman and 15 more

Open access · bronzeAbstract read
In one paragraph

Article in Clinical chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 25% 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

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors at 1 institution in 1 country.

Hui ChenDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Zhao LiDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Sheng FengDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Melissa Richard-GreenblattDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Emily HutsonDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Stefen AndrianusDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Laurel J GlaserDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Kyle G RodinoDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Jianing QianDepartment of Computer and Information Science and GRASP Lab, University of Pennsylvania, Philadelphia, PA, USA.
Dinesh JayaramanDepartment of Computer and Information Science and GRASP Lab, University of Pennsylvania, Philadelphia, PA, USA.
Ronald G CollmanDepartment of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Abigail GlascockDepartment of Microbiology and Penn Center for Research on Coronavirus and Other Emerging Pathogens, University of Pennsylvania, Philadelphia, PA, USA.
Frederic D BushmanDepartment of Microbiology and Penn Center for Research on Coronavirus and Other Emerging Pathogens, University of Pennsylvania, Philadelphia, PA, USA.
Jae Seung LeeDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Sara CherryDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Alejandra FaustoDepartment of Microbiology and Penn Center for Research on Coronavirus and Other Emerging Pathogens, University of Pennsylvania, Philadelphia, PA, USA.
Susan R WeissDepartment of Microbiology and Penn Center for Research on Coronavirus and Other Emerging Pathogens, University of Pennsylvania, Philadelphia, PA, USA.
Hyun KooDepartment of Orthodontics, Divisions of Pediatric Dentistry and Community of Oral Health, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Patricia M CorbyDepartment of Orthodontics, Divisions of Pediatric Dentistry and Community of Oral Health, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Alfonso OcegueraDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Una O'DohertyDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Alfred L GarfallDepartment of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Dan T VoglDepartment of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Edward A StadtmauerDepartment of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Ping WangDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
University of Pennsylvania · US

Funding

Virus & Reservoirs CoreP30AI045008 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI ROBERT GROSS · 1999 to 2026
$78.6M
TRAINING IN VIROLOGYT32AI007324 · NIAID · WISTAR INSTITUTE · PI Paul Bates, Matthew D. Weitzman · 1989 to 2026
$6.8M
Defining the functional interface between the ER and flavivirusesR01AI140539 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI CHERRY, SARA, DIAMOND, MICHAEL S · 2018 to 2022
$3.0M
The Lung DNA Virome in Health and DiseaseR33HL137063 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI BUSHMAN, FREDERIC D, COLLMAN, RONALD G · 2019 to 2021
$2.3M
SCH: Monitoring safety and adherence of pain management though remote opioidR01EB029363 · NIBIB · UNIVERSITY OF PENNSYLVANIA · PI LEE, INSUP, WANG, PING · 2019 to 2022
$902k
Bill & Melinda Gates Foundation INV-018479NHLBI NIH HHS R33 HL137063NIAID NIH HHS P30 AI045008NIAID NIH HHS R01 AI140539NIAID NIH HHS T32 AI007324NIBIB NIH HHS R01 EB029363NIH HHS 3R01AI150246-01S1
6 · The paper itself

Abstract

backgroundHigh-sensitivity severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen assays are desirable to mitigate false negative results. Limited data are available to quantify and track SARS-CoV-2 antigen burden in respiratory samples from different populations.

methodsWe developed the Microbubbling SARS-CoV-2 Antigen Assay (MSAA) with smartphone readout, with a limit of detection of 0.5 pg/mL (10.6 fmol/L) nucleocapsid antigen or 4000 copies/mL inactivated SARS-CoV-2 virus in nasopharyngeal (NP) swabs. We developed a computer vision and machine learning-based automatic microbubble image classifier to accurately identify positives and negatives and quantified and tracked antigen dynamics in intensive care unit coronavirus disease 2019 (COVID-19) inpatients and immunocompromised COVID-19 patients.

resultsCompared to qualitative reverse transcription-polymerase chain reaction methods, the MSAA demonstrated a positive percentage agreement of 97% (95% CI 92%-99%) and a negative percentage agreement of 97% (95% CI 94%-100%) in a clinical validation study with 372 residual clinical NP swabs. In immunocompetent individuals, the antigen positivity rate in swabs decreased as days-after-symptom-onset increased, despite persistent nucleic acid positivity. Antigen was detected for longer and variable periods of time in immunocompromised patients with hematologic malignancies. Total microbubble volume, a quantitative marker of antigen burden, correlated inversely with cycle threshold values and days-after-symptom-onset. Viral sequence variations were detected in patients with long duration of high antigen burden.

conclusionsThe MSAA enables sensitive and specific detection of acute infections and quantification and tracking of antigen burden and may serve as a screening method in longitudinal studies to identify patients who are likely experiencing active rounds of ongoing replication and warrant close viral sequence monitoring.

Indexed as

COVID-19SmartphoneAntigens, ViralCOVID-19 TestingHumansMachine LearningSARS-CoV-2Sensitivity and SpecificityAntigens, Virallongitudinal NP swab samplesmicrobubbling assaySARS-CoV-2viral antigen

Identifiers

PMID34383886
PMCPMC8436368
OpenAlexW3189254779

What OpenQuestion holds

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Registered trials

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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.