Evidence map›Paper›PMID 34229274›Full record

ArticleEBioMedicine2021

A mass spectrometry-based targeted assay for detection of SARS-CoV-2 antigen from clinical specimens.

Santosh Renuse, Patrick M Vanderboom, Anthony D Maus, Jennifer V Kemp, Kari M Gurtner, Anil K Madugundu, Sandip Chavan, Jane A Peterson, Benjamin J Madden, Kiran K Mangalaparthi and 7 more

Abstract read
In one paragraph

Article in EBioMedicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

36 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. A bireporter recombinant SARS-CoV-2 Omicron BA.5 forbioRxiv : the preprint server for biology · 2026
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  17. Advances in rapid detection of SARS-CoV-2 by mass spectrometry.Trends in analytical chemistry : TRAC · 2022
    Review
  18. Article
  19. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Santosh RenuseDepartment of Laboratory Medicine and Pathology, Division of Clinical Biochemistry and Immunology, Mayo Clinic, MN 55905, USA; Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA.
Patrick M VanderboomDepartment of Laboratory Medicine and Pathology, Division of Clinical Biochemistry and Immunology, Mayo Clinic, MN 55905, USA.
Anthony D MausDepartment of Laboratory Medicine and Pathology, Division of Clinical Biochemistry and Immunology, Mayo Clinic, MN 55905, USA.
Jennifer V KempDepartment of Laboratory Medicine and Pathology, Division of Clinical Biochemistry and Immunology, Mayo Clinic, MN 55905, USA.
Kari M GurtnerDepartment of Laboratory Medicine and Pathology, Division of Clinical Biochemistry and Immunology, Mayo Clinic, MN 55905, USA.
Anil K MadugunduDepartment of Laboratory Medicine and Pathology, Division of Clinical Biochemistry and Immunology, Mayo Clinic, MN 55905, USA; Institute of Bioinformatics, International Technology Park, Bangalore, Karnataka 560066, India; Manipal Academy of Higher Education, Manipal, Karnataka 576104, India; Center for Molecular Medicine, National Institute of Mental Health and Neurosciences, Hosur Road, Bangalore, Karnataka 560029, India.
Sandip ChavanDepartment of Laboratory Medicine and Pathology, Division of Clinical Biochemistry and Immunology, Mayo Clinic, MN 55905, USA.
Jane A PetersonProteomics Core, Medical Genome Facility, Mayo Clinic, Rochester, MN 55905, USA.
Benjamin J MaddenProteomics Core, Medical Genome Facility, Mayo Clinic, Rochester, MN 55905, USA.
Kiran K MangalaparthiDepartment of Laboratory Medicine and Pathology, Division of Clinical Biochemistry and Immunology, Mayo Clinic, MN 55905, USA; Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, Kerala 690525, India.
Dong-Gi MunDepartment of Laboratory Medicine and Pathology, Division of Clinical Biochemistry and Immunology, Mayo Clinic, MN 55905, USA.
Smrita SinghDepartment of Laboratory Medicine and Pathology, Division of Clinical Biochemistry and Immunology, Mayo Clinic, MN 55905, USA; Institute of Bioinformatics, International Technology Park, Bangalore, Karnataka 560066, India; Manipal Academy of Higher Education, Manipal, Karnataka 576104, India; Center for Molecular Medicine, National Institute of Mental Health and Neurosciences, Hosur Road, Bangalore, Karnataka 560029, India.
Benjamin R KippDepartment of Laboratory Medicine and Pathology, Division of Laboratory Genetics and Genomics, Mayo Clinic, Rochester, MN 55905, USA.
Surendra DasariDivision of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA.
Ravinder J SinghDepartment of Laboratory Medicine and Pathology, Division of Clinical Biochemistry and Immunology, Mayo Clinic, MN 55905, USA. Electronic address: singh.ravinder@mayo.edu.
Stefan K GrebeDepartment of Laboratory Medicine and Pathology, Division of Clinical Biochemistry and Immunology, Mayo Clinic, MN 55905, USA; Department of Medicine, Division of Endocrinology, Mayo Clinic, Rochester, MN 55902, USA. Electronic address: grebe.stefan@mayo.edu.
Akhilesh PandeyDepartment of Laboratory Medicine and Pathology, Division of Clinical Biochemistry and Immunology, Mayo Clinic, MN 55905, USA; Center for Individualized Medicine, Mayo Clinic, Rochester, MN 55905, USA; Center for Molecular Medicine, National Institute of Mental Health and Neurosciences, Hosur Road, Bangalore, Karnataka 560029, India. Electronic address: pandey.akhilesh@mayo.edu.

Funding

Wellcome Trust
6 · The paper itself

Abstract

backgroundThe COVID-19 pandemic caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) has overwhelmed health systems worldwide and highlighted limitations of diagnostic testing. Several types of diagnostic tests including RT-PCR-based assays and antigen detection by lateral flow assays, each with their own strengths and weaknesses, have been developed and deployed in a short time.

methodsHere, we describe an immunoaffinity purification approach followed a by high resolution mass spectrometry-based targeted qualitative assay capable of detecting SARS-CoV-2 viral antigen from nasopharyngeal swab samples. Based on our discovery experiments using purified virus, recombinant viral protein and nasopharyngeal swab samples from COVID-19 positive patients, nucleocapsid protein was selected as a target antigen. We then developed an automated antibody capture-based workflow coupled to targeted high-field asymmetric waveform ion mobility spectrometry (FAIMS) - parallel reaction monitoring (PRM) assay on an Orbitrap Exploris 480 mass spectrometer. An ensemble machine learning-based model for determining COVID-19 positive samples was developed using fragment ion intensities from the PRM data.

findingsThe optimized targeted assay, which was used to analyze 88 positive and 88 negative nasopharyngeal swab samples for validation, resulted in 98% (95% CI = 0.922-0.997) (86/88) sensitivity and 100% (95% CI = 0.958-1.000) (88/88) specificity using RT-PCR-based molecular testing as the reference method.

interpretationOur results demonstrate that direct detection of infectious agents from clinical samples by tandem mass spectrometry-based assays have potential to be deployed as diagnostic assays in clinical laboratories, which has hitherto been limited to analysis of pure microbial cultures.

fundingThis study was supported by DBT/Wellcome Trust India Alliance Margdarshi Fellowship grant IA/M/15/1/502023 awarded to AP and the generosity of Eric and Wendy Schmidt.

Indexed as

AnimalsAntigens, ViralAutomation, LaboratoryChlorocebus aethiopsCoronavirus Nucleocapsid ProteinsCOVID-19 Serological TestingHumansImmunoassayMachine LearningMass SpectrometryPhosphoproteinsSensitivity and SpecificityAntigens, ViralCoronavirus Nucleocapsid Proteinsnucleocapsid phosphoprotein, SARS-CoV-2PhosphoproteinsCOVID-19Diagnostic assaysIon mobilityMachine learningMass spectrometrySARS-CoV-2

Identifiers

PMID34229274
PMCPMC8253671

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.