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Cited by 129SARS-CoV-2 detection and testingSARS-CoV-2 and COVID-19 ResearchCOVID-19 Clinical Research Studies

The DOI matches its Crossref record; 31 of the 32 references it cites were found in a registry or an index.

Multi-center nationwide comparison of seven serology assays reveals a SARS-CoV-2 non-responding seronegative subpopulation

Open access
Oved, Kfir, Olmer, Liraz, Shemer-Avni, Yonat, Wolf, Tamar, Supino-Rosin, Lia, Prajgrod, George, Shenhar, Yotam, Payorsky, Irina, Cohen, Yuval, Kohn, Yishai, Indenbaum, Victoria, Lazar, Rachel, Geylis, Valeria, Oikawa, Michal Tepperberg, Shinar, Eilat, Stoyanov, Evgeniy, Keinan-Boker, Lital, Bassal, Ravit, Reicher, Shay, Yishai, Ruti, Bar-Chaim, Adina, Doolman, Ram, Reiter, Yoram, Mendelson, Ella, Livneh, Zvi, Freedman, Laurence S., Lustig, Yaniv·2020·EClinicalMedicine
DOI 10.1016/j.eclinm.2020.100651PMC PMC7676374
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Abstract

BACKGROUND: An Israeli national taskforce performed a multi-center clinical and analytical validation of seven serology assays to determine their utility and limitations for SARS-CoV-2 diagnosis. METHODS: Serology assays from Roche, Abbott, Diasorin, BioMerieux, Beckman-Coulter, Siemens, and an in-house RBD ELISA were included. Negative samples from 2391 individuals representative of the Israeli population, and 698 SARS-CoV-2 PCR positive patients, collected between March and May 2020, were analyzed. FINDINGS: Immunoassays sensitivities between 81.5%-89.4% and specificities between 97.7%-100% resulted in a profound impact on the expected Positive Predictive Value (PPV) in low (<15%) prevalence scenarios. No meaningful increase was detected in the false positive rate in children compared to adults. A positive correlation between disease severity and antibody titers, and no decrease in antibody titers in the first 8 weeks after PCR positivity was observed. We identified a subgroup of symptomatic SARS-CoV-2 positive patients (~5% of patients), who remained seronegative across a wide range of antigens, isotypes, and technologies. INTERPRETATION: The commercially available automated immunoassays exhibit significant differences in performance and expected PPV in low prevalence scenarios. The low false-positivity rate in under 20's suggests that cross-reactive immunity from previous CoV strains is unlikely to explain the milder disease course in children. Finding no decrease in antibody titers in the first 8 weeks is in contrast to some reports of short half-life for SARS-CoV-2 antibodies. The ~5% who were seronegative non-responders, using multiple assays in a population-wide manner, represents the proportion of patients that may be at risk for re-infection. FUNDING: Israel Ministry of Health.

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CC-BY-NC-ND · From the PDF
Fig. 1 Study selection process, total number of patients that were included and excluded, and details on the size of each tested group and kits based on the STARD guidelines. Out of 3098 available samples, 3089 samples were included in the study. Number of SARS-CoV-2 PCR positive (equal or above or below 14 days after fi rst positive PCR) and negative samples tested with each of the serology assays are presented.
Fig. 1 Study selection process, total number of patients that were included and excluded, and details on the size of each tested group and kits based on the STARD guidelines. Out of 3098 available samples, 3089 samples were included in the study. Number of SARS-CoV-2 PCR positive (equal or above or below 14 days after fi rst positive PCR) and negative samples tested with each of the serology assays are presented.CC-BY-NC-ND · From the PDF
Fig. 2 Effect of SARS-CoV-2 prevalence on positive predictive values (PPV) of the different assays. The PPV of each assay was calculated and is depicted based on different SARSCoV-2 prevalence in the population ranging between 0.5% and 15%..
Fig. 2 Effect of SARS-CoV-2 prevalence on positive predictive values (PPV) of the different assays. The PPV of each assay was calculated and is depicted based on different SARSCoV-2 prevalence in the population ranging between 0.5% and 15%..CC-BY-NC-ND · From the PDF
Fig. 3 SARS-CoV-2 antibody levels during the fi rst 8 weeks after a positive PCR result. Antibody titer of each sample was recorded for each serological assay. Restricted cubic spline regression line with fi ve knots located at the 10th, 25th, 50th, 75th and 90th percentiles are presented for each immunoassay.
Fig. 3 SARS-CoV-2 antibody levels during the fi rst 8 weeks after a positive PCR result. Antibody titer of each sample was recorded for each serological assay. Restricted cubic spline regression line with fi ve knots located at the 10th, 25th, 50th, 75th and 90th percentiles are presented for each immunoassay.CC-BY-NC-ND · From the PDF

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Research works printed but not linked: 5

  1. Lustig, 2020, Potential antigenic cross-reactivity between SARS-CoV-2 and dengue viruses, Clin Infect Dis
  2. Lynch, 2020, Magnitude and kinetics of anti-SARS-CoV-2 antibody responses and their relationship to disease severity, Clin Infect Dis
  3. Magid, 2020, Health Ministry announces purchase of 2.4 million antibody tests, Times Israel
  4. Kirkpatrick, 2020, Paid $20 million for new coronavirus tests. They didn't work., New York Times.
  5. To, 2020, COVID-19 re-infection by a phylogenetically distinct SARS-coronavirus-2 strain confirmed by whole genome sequencing, Clin Infect Dis

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Metadata

Authors
Oved, K., Olmer, L., Shemer-Avni, Y., Wolf, T., Supino-Rosin, L., Prajgrod, G., Shenhar, Y., Payorsky, I., Cohen, Y., Kohn, Y., Indenbaum, V., Lazar, R., Geylis, V., Oikawa, M. T., Shinar, E., Stoyanov, E., Keinan-Boker, L., Bassal, R., Reicher, S., Yishai, R., Bar-Chaim, A., Doolman, R., Reiter, Y., Mendelson, E., Livneh, Z., Freedman, L. S., & Lustig, Y.
Affiliations
  • Sheba Medical Center (IL)
  • Maccabi Healthcare Services (IL)
  • Ministry of Defense (IL)
  • Magen David Adom (IL)
  • Israel Ministry of Health (IL)
  • Technion – Israel Institute of Technology (IL)
  • Tel Aviv University (IL)
  • Weizmann Institute of Science (IL)
Corresponding author
Lustig, Yaniv
ORCID
Venue
EClinicalMedicine
Publisher
Elsevier BV
Published
2020-12
Volume
29-30
Pages
100651
ISSN
2589-5370 (ISSN-L)
DOI
10.1016/j.eclinm.2020.100651
PMC
PMC7676374
OpenAlex
W3099879565
Cited by
129
References
32
Citations by year
2026: 1 · 2025: 3 · 2024: 5 · 2023: 14 · 2022: 33 · 2021: 71 · 2020: 1
FWCI
3.90
Type
journal article
Language
en
Open access
Licence
Locations
  • EClinicalMedicine (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Ministry of Health, State of Israel
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
Keywords
SARS-CoV-2, immunoassay validation, antibody titers, positive predictive value, low prevalence, children, disease severity, reinfection risk, antibody half-life, immunological cross-reactivity, assay sensitivity and specificity

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