Evaluation of Commercially Available High-Throughput SARS-CoV-2 Serologic Assays for Serosurveillance and Related Applications

Stone, Mars; Grebe, Eduard; Sulaeman, Hasan; Germanio, Clara Di; Dave, Honey; Kelly, Kathleen; Biggerstaff, Brad J.; Crews, Bridgit; Tran, Nam K.; Jerome, Keith R.; Denny, Thomas N.; Hogema, Boris M.; Destree, Mark; Jones, Jefferson M.; Thornburg, Natalie J.; Simmons, Graham; Krajden, Mel; Kleinman, Steve; Dumont, Larry J.; Busch, Michael P.

doi:10.3201/eid2803.211885

Cited by 56 publications

(69 citation statements)

References 27 publications

(28 reference statements)

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“…We suspected that the SARS-CoV-2 infection rate estimated by the seroprevalence of anti-N antibody would be higher than the rate indicated by the PCR-based diagnoses due to the existence of asymptomatically or mildly infected individuals whose cases may not have been detected since they never underwent testing by PCR analysis or antigen test. The anti-N ECLIA used here is a high sensitivity method widely detecting IgG, IgA, and IgM, it has advantage for the use of serosurveillance [ 26 ]. Indeed, the anti-N ECLIA-based infection rates revealed in the present analyses, i.e., 2.1% and 3.9% for August and December 2021, were respectively higher than the rates 0.84% (46,381 cases/5,465 thousand people in Hyogo prefecture as of August 6, 2021) and 1.4% (78,898 cases/5,465 thousand people in Hyogo prefecture as of December 8, 2021) estimated from the reported cases based on PCR diagnoses [ 1 ].…”

Section: Discussionmentioning

confidence: 99%

Large-scale serosurveillance of COVID-19 in Japan: Acquisition of neutralizing antibodies for Delta but not for Omicron and requirement of booster vaccination to overcome the Omicron’s outbreak

et al. 2022

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Continuous appearance of SARS-CoV-2 variants and mass vaccination have been intricately influencing on the COVID-19 situation. To elucidate the current status in Japan, we analyzed totally 2,000 sera in August (n = 1,000) and December (n = 1,000) 2021 collected from individuals who underwent a health check-up. The anti-N seropositive rate were 2.1% and 3.9% in August and December 2021, respectively, demonstrating a Delta variant endemic during that time; it was approximately twofold higher than the rate based on the PCR-based diagnosis. The anti-S seropositive rate was 38.7% in August and it reached 90.8% in December, in concordance with the vaccination rate in Japan. In the December cohort, 78.7% of the sera showed neutralizing activity against the Delta variant, whereas that against the Omicron was much lower at 36.6%. These analyses revealed that effective immunity against the Delta variant was established in December 2021, however, prompt three-dose vaccination is needed to overcome Omicron’s outbreak.

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Section: Discussionmentioning

confidence: 99%

Large-scale serosurveillance of COVID-19 in Japan: Acquisition of neutralizing antibodies for Delta but not for Omicron and requirement of booster vaccination to overcome the Omicron’s outbreak

et al. 2022

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“…This suggests that lower cutoffs could be considered, although further research is needed to define these alternative cutoffs. A recent analysis of UK serosurvey samples recommended a threshold of 0.47 for the detection of vaccine breakthrough infections using the Roche NC assay (11,17). As commercial manufacturers and FDA tend to maximize specificity when setting assay thresholds, sensitivity may be compromised to achieve optimal specificity; thus, specimens with gray zone reactivity likely represent infections.…”

Section: Discussionmentioning

confidence: 99%

“…Some studies utilize lower throughput in-house assays such as ELISAs (7,8), while other studies utilize commercial higher throughput assays from major manufacturers such as Abbott, Roche, Euroimmun, Wantai, and Ortho Clinical Diagnostics (5,9,10). For optimal selection and use of assays in serosurveillance, three performance characteristics are key: sensitivity, specificity, and durability of antibody detection (11). While most commercially available SARS-CoV-2 serological assays have good sensitivity and specificity to support clinical diagnosis of recent infection, durability of antibody detection varies considerably (11,12).…”

Section: Introductionmentioning

confidence: 99%

“…For optimal selection and use of assays in serosurveillance, three performance characteristics are key: sensitivity, specificity, and durability of antibody detection (11). While most commercially available SARS-CoV-2 serological assays have good sensitivity and specificity to support clinical diagnosis of recent infection, durability of antibody detection varies considerably (11,12). Moreover, for larger serosurveillance programs, operational feasibility considerations, such as high throughput testing on fully automated platforms in multiple laboratories and cost, are important considerations in ensuring timely generation and reporting of accurate results.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of Ortho VITROS and Roche Elecsys S and NC Immunoassays for SARS‑CoV‑2 Serosurveillance Applications

Sulaeman,

Grebe,

Dave

et al. 2022

Preprint

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SARS-CoV-2 seroprevalence studies are instrumental in monitoring epidemic activity and require well-characterized, high-throughput assays, and appropriate testing algorithms. The U.S. Nationwide Blood Donor Seroprevalence Study performed monthly cross-sectional serological testing from July 2020 to December 2021, implementing evolving testing algorithms in response to changes in pandemic activity. With high vaccine uptake, anti-Spike (S) reactivity rates reached >80% by May 2021, and the study pivoted from reflex Roche anti-nucleocapsid (NC) testing of Ortho S-reactive specimens to parallel Ortho S/NC testing. We evaluated the performance of the Ortho NC assay as a replacement for the Roche NC assay and compared performance of parallel S/NC testing on both platforms. Qualitative and quantitative agreement of Ortho NC with Roche NC assays was evaluated on pre-selected S/NC concordant and discordant specimens. All 200 Ortho S+/Roche NC+ specimens were reactive on the Ortho NC assay; 36% of 383 Ortho S+/Roche NC- specimens collected prior to vaccine availability and 52% of 101 Ortho S-/Roche NC+ specimens were reactive on the Ortho NC assay. Performance of parallel S/NC testing using Ortho and Roche platforms was evaluated on 200 specimens collected in 2019 and 3,903 study specimens collected in 2021. All 200 pre-COVID 2019 specimens tested negative on the four assays. Agreement of S and NC reactivity on specimens was 96.4% (3,769/3,903); most discordant results had reactivity close to the cutoffs on the alternate assays. These findings, and higher efficiency and throughput, support use of parallel S/NC testing on either Roche or Ortho platforms for large serosurveillance studies.

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“…We used a chemiluminescent microparticle immunoassay (CIMA, AdviseDx, Abbott) that detects IgG antibodies against the SARS-CoV-2 spike (S) protein. At a threshold of 50 S/C units, we have previously shown this assay to have a sensitivity of 94.0% in 208 non-hospitalized PCR-positive convalescent individuals, and its specificity is >99% [15].…”

Section: Methodsmentioning

confidence: 99%

Predicting SARS-CoV-2 variant spread in a completely seropositive population using semi-quantitative antibody measurements in blood donors

Buss

Prete

Whittaker

et al. 2022

Preprint

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Background SARS-CoV-2 serologic surveys estimate the proportion of the population with antibodies against historical variants which nears 100% in many settings. New analytic approaches are required to exploit the full information in serosurvey data. Method Using a SARS-CoV-2 anti-Spike (S) protein chemiluminescent microparticle assay, we attained a semi-quantitative measurement of population IgG titres in serial cross-sectional monthly samples of routine blood donations across seven Brazilian state capitals (March 2021-November 2021). In an ecological analysis (unit of analysis: age-city-calendar month) we assessed the relative contributions of prior attack rate and vaccination to antibody titre in blood donors. We compared blood donor anti-S titre across the seven cities during the growth phase of the Delta variant of concern (VOC) and use this to predict the resulting age-standardized incidence of severe COVID-19 cases. Results On average we tested 780 samples per month in each location. Seroprevalence rose to >95% across all seven capitals by November 2021. Driven proximally by vaccination, mean antibody titre increased 16-fold over the study. The extent of prior natural infection shaped this process, with the greatest increases in antibody titres occurring in cities with the highest prior attack rates. Mean anti-S IgG was a strong predictor (adjusted R2 =0.89) of the number of severe cases caused by the Delta VOC in the seven cities. Conclusions Semi-quantitative anti-S antibody titres are informative about prior exposure and vaccination coverage and can inform on the potential impact of future SARS-CoV-2 variants.

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Evaluation of Commercially Available High-Throughput SARS-CoV-2 Serologic Assays for Serosurveillance and Related Applications

Cited by 56 publications

References 27 publications

Large-scale serosurveillance of COVID-19 in Japan: Acquisition of neutralizing antibodies for Delta but not for Omicron and requirement of booster vaccination to overcome the Omicron’s outbreak

Large-scale serosurveillance of COVID-19 in Japan: Acquisition of neutralizing antibodies for Delta but not for Omicron and requirement of booster vaccination to overcome the Omicron’s outbreak

Evaluation of Ortho VITROS and Roche Elecsys S and NC Immunoassays for SARS‑CoV‑2 Serosurveillance Applications

Predicting SARS-CoV-2 variant spread in a completely seropositive population using semi-quantitative antibody measurements in blood donors

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