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

被引：105

作者：

Oved, Kfir ^{[1
]}

Olmer, Liraz ^{[2
]}

Shemer-Avni, Yonat ^{[3
,4
]}

Wolf, Tamar ^{[5
]}

Supino-Rosin, Lia ^{[5
]}

Prajgrod, George ^{[6
]}

Shenhar, Yotam ^{[7
]}

Payorsky, Irina ^{[7
]}

Cohen, Yuval ^{[8
]}

Kohn, Yishai ^{[8
]}

Indenbaum, Victoria ^{[9
]}

Lazar, Rachel ^{[5
]}

Geylis, Valeria ^{[5
]}

Oikawa, Michal Tepperberg ^{[9
]}

Shinar, Eilat ^{[10
]}

Stoyanov, Evgeniy ^{[10
]}

Keinan-Boker, Lital ^{[11
,12
]}

Bassal, Ravit ^{[11
]}

Reicher, Shay ^{[13
]}

Yishai, Ruti ^{[13
,18
]}

Bar-Chaim, Adina ^{[14
]}

Doolman, Ram ^{[15
]}

Reiter, Yoram ^{[16
]}

Mendelson, Ella ^{[9
,12
]}

Livneh, Zvi ^{[17
]}

Freedman, Laurence S. ^{[2
]}

Lustig, Yaniv ^{[9
]}

机构：

[1] Canopy Immunotherapeut & MeMed Diagnost, Tirat Carmel, Israel

[2] Sheba Med Ctr, Gertner Inst Epidemiol & Hlth Policy Res, Tel Hashomer, Israel

[3] Lab Clin Virol Clalit HMO, Beer Sheva, Israel

[4] Soroka Med Ctr, Beer Sheva, Israel

[5] Maccabi HMO, Lab Div, Rehovot, Israel

[6] Meuhedet HMO, Lab Div, Rehovot, Israel

[7] Leumit HMO, Lab Div, Or Yehuda, Israel

[8] Minist Def, Directorate Def Res & Dev, Tel Aviv, Israel

[9] Minist Hlth & Sheba Med Ctr, Cent Virol Lab, Tel Hashomer, Israel

[10] Magen David Natl Blood Serv, Tel Hashomer, Israel

[11] Chaim Sheba Med Ctr, Israel Ctr Dis Control, Minist Hlth, Tel Hashomer, Israel

[12] Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel

[13] Minist Hlth, Jerusalem, Israel

[14] Asaaf Harofeh Med Ctr, Beer Yaagov, Israel

[15] Sheba Med Ctr, Tel Hashomer, Israel

[16] Technion Israel Inst Technol, Haifa, Israel

[17] Weizmann Inst Sci, Dept Biomol Sci, Rehovot, Israel

[18] Minist Hlth, Publ Hlth Serv, Dept Labs, Jerusalem, Israel

来源：

ECLINICALMEDICINE | 2020年 / 29-30卷

关键词：

COVID-19; Serology; SARS-CoV-2; Antibodies; Validation study; Seronegative subpopulation; IgG;

D O I：

10.1016/j.eclinm.2020.100651

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 (similar to 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 200s 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 similar to 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. (c) 2020 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

引用

页数：10

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