TY - JOUR
T1 - Multi-center nationwide comparison of seven serology assays reveals a SARS-CoV-2 non-responding seronegative subpopulation
AU - Oved, Kfir
AU - Olmer, Liraz
AU - Shemer-Avni, Yonat
AU - Wolf, Tamar
AU - Supino-Rosin, Lia
AU - Prajgrod, George
AU - Shenhar, Yotam
AU - Payorsky, Irina
AU - Cohen, Yuval
AU - Kohn, Yishai
AU - Indenbaum, Victoria
AU - Lazar, Rachel
AU - Geylis, Valeria
AU - Oikawa, Michal Tepperberg
AU - Shinar, Eilat
AU - Stoyanov, Evgeniy
AU - Keinan-Boker, Lital
AU - Bassal, Ravit
AU - Reicher, Shay
AU - Yishai, Ruti
AU - Bar-Chaim, Adina
AU - Doolman, Ram
AU - Reiter, Yoram
AU - Mendelson, Ella
AU - Livneh, Zvi
AU - Freedman, Laurence S.
AU - Lustig, Yaniv
N1 - Publisher Copyright:
© 2020 The Authors
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
KW - Antibodies
KW - COVID-19
KW - IgG
KW - SARS-CoV-2
KW - Serology
KW - Seronegative subpopulation
KW - Validation study
UR - http://www.scopus.com/inward/record.url?scp=85096463897&partnerID=8YFLogxK
U2 - 10.1016/j.eclinm.2020.100651
DO - 10.1016/j.eclinm.2020.100651
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AN - SCOPUS:85096463897
SN - 2589-5370
VL - 29-30
JO - EClinicalMedicine
JF - EClinicalMedicine
M1 - 100651
ER -