Validation of a SARS-CoV-2 spike protein ELISA for use in contact investigations and sero-surveillance

Freeman, Brandi; Lester, Sandra; Mills, Lisa; Rasheed, Mohammad Ata Ur; Moye, Stefany; Abiona, Olubukola M.; Hutchinson, Geoffrey B.; Morales-Betoulle, Maria; Krapinunaya, Inna; Gibbons, Ardith; Chiang, Cheng‐Feng; Cannon, Deborah; Klena, John D.; Johnson, Jeffrey A.; Owen, Sherry Michelle; Graham, Barney S.; Corbett, Kizzmekia S.; Thornburg, Natalie J.

doi:10.1101/2020.04.24.057323

“…In total, 4696 records based on screening of titles or abstracts and 235 after full text review were excluded. Forty studies totalling 73 study arms15161718192021222324252627282930313233343536373839404142434445464748495051525354 met the inclusion criteria. Table 1 summarises the studies by test method; the sum of the number of studies exceeds 40 because some evaluated more than one method.…”

Section: Resultsmentioning

confidence: 99%

“…Table 1 summarises the studies by test method; the sum of the number of studies exceeds 40 because some evaluated more than one method. Seventy per cent (28/40) of the studies were from China,16171819202122232425262728293031323334353839404145464748 8% (3/40) from Italy,153643 and the remainder from the United States (3/40),425052 Denmark (1/40),51 Spain (1/40),37 Sweden (1/40),53 Japan (1/40),44 the United Kingdom (1/40),49 and Germany (1/40) 5433…”

Section: Resultsmentioning

confidence: 99%

Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis

Bastos

¹

,

Tavaziva

²

,

Abidi

³

et al. 2020

BMJ

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AbstractObjectiveTo determine the diagnostic accuracy of serological tests for coronavirus disease-2019 (covid-19).DesignSystematic review and meta-analysis.Data sourcesMedline, bioRxiv, and medRxiv from 1 January to 30 April 2020, using subject headings or subheadings combined with text words for the concepts of covid-19 and serological tests for covid-19.Eligibility criteria and data analysisEligible studies measured sensitivity or specificity, or both of a covid-19 serological test compared with a reference standard of viral culture or reverse transcriptase polymerase chain reaction. Studies were excluded with fewer than five participants or samples. Risk of bias was assessed using quality assessment of diagnostic accuracy studies 2 (QUADAS-2). Pooled sensitivity and specificity were estimated using random effects bivariate meta-analyses.Main outcome measuresThe primary outcome was overall sensitivity and specificity, stratified by method of serological testing (enzyme linked immunosorbent assays (ELISAs), lateral flow immunoassays (LFIAs), or chemiluminescent immunoassays (CLIAs)) and immunoglobulin class (IgG, IgM, or both). Secondary outcomes were stratum specific sensitivity and specificity within subgroups defined by study or participant characteristics, including time since symptom onset.Results5016 references were identified and 40 studies included. 49 risk of bias assessments were carried out (one for each population and method evaluated). High risk of patient selection bias was found in 98% (48/49) of assessments and high or unclear risk of bias from performance or interpretation of the serological test in 73% (36/49). Only 10% (4/40) of studies included outpatients. Only two studies evaluated tests at the point of care. For each method of testing, pooled sensitivity and specificity were not associated with the immunoglobulin class measured. The pooled sensitivity of ELISAs measuring IgG or IgM was 84.3% (95% confidence interval 75.6% to 90.9%), of LFIAs was 66.0% (49.3% to 79.3%), and of CLIAs was 97.8% (46.2% to 100%). In all analyses, pooled sensitivity was lower for LFIAs, the potential point-of-care method. Pooled specificities ranged from 96.6% to 99.7%. Of the samples used for estimating specificity, 83% (10 465/12 547) were from populations tested before the epidemic or not suspected of having covid-19. Among LFIAs, pooled sensitivity of commercial kits (65.0%, 49.0% to 78.2%) was lower than that of non-commercial tests (88.2%, 83.6% to 91.3%). Heterogeneity was seen in all analyses. Sensitivity was higher at least three weeks after symptom onset (ranging from 69.9% to 98.9%) compared with within the first week (from 13.4% to 50.3%).ConclusionHigher quality clinical studies assessing the diagnostic accuracy of serological tests for covid-19 are urgently needed. Currently, available evidence does not support the continued use of existing point-of-care serological tests.Study registrationPROSPERO CRD42020179452.

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“…Laboratory tested respiratory specimens using the CDC 2019-nCoV real-time RT-PCR assay 12 and processed and shipped blood specimens to CDC for serology testing using the CDC SARS-CoV-2 spike protein enzyme-linked immunosorbent assay (ELISA). 13…”

Section: The City Of Milwaukee Health Department Laboratory and The Umentioning

confidence: 99%

Symptoms and Transmission of SARS-CoV-2 Among Children — Utah and Wisconsin, March–May 2020

Laws

¹

,

Chancey

²

,

Rabold

³

et al. 2021

Self Cite

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This is a prepublication version of an article that has undergone peer review and been accepted for publication but is not the final version of record. This paper may be cited using the DOI and date of access. This paper may contain information that has errors in facts, figures, and statements, and will be corrected in the final published version. The journal is providing an early version of this article to expedite access to this information. The American Academy of Pediatrics, the editors, and authors are not responsible for inaccurate information and data described in this version.

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“…Archival sera from subjects with PCR-confirmed seasonal coronaviruses exhibit cross-reactivity with SARS-CoV-2 spike proteinDespite low sequence similarity and identity between SARS-CoV-2 spike protein and seasonal HCoV spike proteins, antibody cross-reactivity with SARS-CoV-2 proteins has been observed(14,15). To determine whether prior infection with seasonal HCoV induces antibodies that cross-react with SARS-CoV-2, we assayed archival (pre-2019) serum from human subjects with PCR-confirmed seasonal HCoVs.…”

mentioning

confidence: 99%

A betacoronavirus multiplex microsphere immunoassay detects early SARS-CoV-2 seroconversion and controls for pre-existing seasonal human coronavirus antibody cross-reactivity

Laing

¹

,

Sterling

²

,

Richard

³

et al. 2020

Preprint

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With growing concern of persistent or multiple waves of SARS-CoV-2 in the United States, sensitive and specific SARS-CoV-2 antibody assays remain critical for community and hospital-based SARS-CoV-2 surveillance. Here, we describe the development and application of a multiplex microsphere-based immunoassay (MMIA) for COVD-19 antibody studies, utilizing serum samples from non-human primate SARS-CoV-2 infection models, an archived human sera bank and subjects enrolled at five U.S. military hospitals. The MMIA incorporates prefusion stabilized spike glycoprotein trimers of SARS-CoV-2, SARS-CoV-1, MERS-CoV, and the seasonal human coronaviruses HCoV-HKU1 and HCoV-OC43, into a multiplexing system that enables simultaneous measurement of off-target pre-existing cross-reactive antibodies. We report the sensitivity and specificity performances for this assay strategy at 98% sensitivity and 100% specificity for subject samples collected as early as 10 days after the onset of symptoms. In archival sera collected prior to 2019 and serum samples from subjects PCR negative for SARS-CoV-2, we detected seroprevalence of 72% and 98% for HCoV-HKU1 and HCoV-0C43, respectively. Requiring only 1.25 uL of sera, this approach permitted the simultaneous identification of SARS-CoV-2 seroconversion and polyclonal SARS-CoV-2 IgG antibody responses to SARS-CoV-1 and MERS-CoV, further demonstrating the presence of conserved epitopes in the spike glycoprotein of zoonotic betacoronaviruses. Application of this serology assay in observational studies with serum samples collected from subjects before and after SARS-CoV-2 infection will permit an investigation of the influences of HCoV-induced antibodies on COVID-19 clinical outcomes.

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Validation of a SARS-CoV-2 spike protein ELISA for use in contact investigations and sero-surveillance

Cited by 95 publications

References 13 publications

Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis

Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis

Symptoms and Transmission of SARS-CoV-2 Among Children — Utah and Wisconsin, March–May 2020

A betacoronavirus multiplex microsphere immunoassay detects early SARS-CoV-2 seroconversion and controls for pre-existing seasonal human coronavirus antibody cross-reactivity

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