K. Oved, L. Olmer, Y. Shemer-Avni, T. Wolf, L. Supino-Rosin, G. Prajgrod, Y. Shenhar, Irina Payorsky, Y. Cohen, Yishai Kohn, V. Indenbaum, R. Lazar, Valeria Geylis, Michal Teperberg Oikawa, E. Shinar, Evgeniy Stoyanov, L. Keinan-Boker, R. Bassal, S. Reicher, Ruti Yishai, A. Bar-Chaim, R. Doolman, Y. Reiter, E. Mendelson, Z. Livneh, L. Freedman, Y. Lustig
EClinicalMedicine, 2020
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 Mt.-Sinai 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 wThe 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.
Cited by 55 publications.
Field of study: Medicine