Evidence map›Paper›PMID 34321523›Full record

ArticleScientific reports2021

A surrogate virus neutralization test to quantify antibody-mediated inhibition of SARS-CoV-2 in finger stick dried blood spot samples.

Amelia E Sancilio, Richard T D'Aquila, Elizabeth M McNally, Matthew P Velez, Michael G Ison, Alexis R Demonbreun, Thomas W McDade

Registry-linked trialAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06939556 (Development of a High-throughput Serological Testing Platform for Mass Screening Purposes of Both Pediatric and Adult Cohorts), which is not on this map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
–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.

NCT06939556 recruitingnot on this mapstarted 2025, after this paper: background citation

Development of a High-throughput Serological Testing Platform for Mass Screening Purposes of Both Pediatric and Adult Cohorts

TypeobservationalSponsorIstituto Zooprofilattico Sperimentale delle VenezieRan2025 to 2025Enrolled152ConditionsDiagnostics, Pandemic Response
3 · Its place in the literature

Who cites it

28 citing papers in PubMed.

  1. Article
  2. Article
  3. RSV Neutralizing Antibodies in Dried Blood.The Journal of infectious diseases · 2024
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. Article
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  15. Review
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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

7 authors.

Amelia E SancilioInstitute for Policy Research, Northwestern University, Evanston, USA.
Richard T D'AquilaDivision of Infectious Diseases, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, USA.
Elizabeth M McNallyCenter for Genetic Medicine, Northwestern University, Evanston, USA.
Matthew P VelezCenter for Genetic Medicine, Northwestern University, Evanston, USA.
Michael G IsonDivision of Infectious Diseases, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, USA.
Alexis R DemonbreunCenter for Genetic Medicine, Northwestern University, Evanston, USA.
Thomas W McDadeInstitute for Policy Research, Northwestern University, Evanston, USA. t-mcdade@northwestern.edu.

Funding

Northwestern University Clinical and Translational Science Institute (NUCATS)UL1TR001422 · NCATS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI D'AQUILA, RICHARD · 2015 to 2023
$56.8M
SPECIALIZED TRAINING PROGRAM IN THE DEMOGRAPHY &ECON.T32AG000243 · NIA · UNIVERSITY OF CHICAGO · PI DAVID O MELTZER · 1994 to 2026
$8.2M
National Science Foundation 2035114NCATS NIH HHS UL1 TR001422NIA NIH HHS T32 AG000243NIH HHS UL1TR001422
6 · The paper itself

Abstract

The spike protein of SARS-CoV-2 engages the human angiotensin-converting enzyme 2 (ACE2) receptor to enter host cells, and neutralizing antibodies are effective at blocking this interaction to prevent infection. Widespread application of this important marker of protective immunity is limited by logistical and technical challenges associated with live virus methods and venous blood collection. To address this gap, we validated an immunoassay-based method for quantifying neutralization of the spike-ACE2 interaction in a single drop of capillary whole blood, collected on filter paper as a dried blood spot (DBS) sample. Samples are eluted overnight and incubated in the presence of spike antigen and ACE2 in a 96-well solid phase plate. Competitive immunoassay with electrochemiluminescent label is used to quantify neutralizing activity. The following measures of assay performance were evaluated: dilution series of confirmed positive and negative samples, agreement with results from matched DBS-serum samples, analysis of results from DBS samples with known COVID-19 status, and precision (intra-assay percent coefficient of variation; %CV) and reliability (inter-assay; %CV). Dilution series produced the expected pattern of dose-response. Agreement between results from serum and DBS samples was high, with concordance correlation = 0.991. Analysis of three control samples across the measurement range indicated acceptable levels of precision and reliability. Median % surrogate neutralization was 46.9 for PCR confirmed convalescent COVID-19 samples and 0.1 for negative samples. Large-scale testing is important for quantifying neutralizing antibodies that can provide protection against COVID-19 in order to estimate the level of immunity in the general population. DBS provides a minimally-invasive, low cost alternative to venous blood collection, and this scalable immunoassay-based method for quantifying inhibition of the spike-ACE2 interaction can be used as a surrogate for virus-based assays to expand testing across a wide range of settings and populations.

Indexed as

Angiotensin-Converting Enzyme 2Antibodies, BlockingAntibodies, ViralCOVID-19COVID-19 Serological TestingDried Blood Spot TestingHumansImmunoassayNeutralization TestsReproducibility of ResultsSARS-CoV-2Serologic TestsSpike Glycoprotein, CoronavirusACE2 protein, humanAngiotensin-Converting Enzyme 2Antibodies, BlockingAntibodies, ViralSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2

Identifiers

PMID34321523
PMCPMC8319431

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Registered trials

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.