Multi-center nationwide comparison of seven serology assays reveals a SARS-CoV-2 non-responding seronegative subpopulation. (December 2020)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: EClinicalMedicine. Volume 29/30(2020)
• Publication Date: 2020-12
• Subjects: COVID-19 -- Serology -- SARS-CoV-2 -- Antibodies -- Validation study -- Seronegative subpopulation -- IgG; Medicine -- Research -- Periodicals; Medical policy -- Periodicals; Clinical Medicine; Health Policy; Public Health; Medical policy; Medicine -- Research; Periodical; Electronic journals; Periodicals; 613
• DOI: 10.1016/j.eclinm.2020.100651
• Languages: English
• ISSNs: 2589-5370

Abstract

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.