Test performance evaluation of SARS-CoV-2 serological assays

Jeffrey D. Whitman(University of California, San Francisco), Joseph Hiatt(Gladstone Institutes), Cody T. Mowery(University of California, San Francisco), Brian R. Shy(University of California, San Francisco), Ruby Yu(University of California, San Francisco), Tori N. Yamamoto(University of California, San Francisco), Ujjwal Rathore(Gladstone Institutes), Gregory M. Goldgof(University of California, San Francisco), Caroline Whitty(University of California, San Francisco), Jonathan M. Woo(University of California, San Francisco), Antonia E. Gallman(Howard Hughes Medical Institute), Tyler E. Miller(Harvard University), Andrew G. Levine(University of California, San Francisco), David N. Nguyen(University of California, San Francisco), Sagar P. Bapat(University of California, San Francisco), Joanna Balcerek(University of California, San Francisco), Sophia Bylsma(University of California, Berkeley), Ana M. Lyons(University of California, Berkeley), Stacy Li(University of California, Berkeley), Allison Wai-yi Wong(University of California, San Francisco), Eva Mae Gillis-Buck(University of California, San Francisco), Zachary Steinhart(University of California, San Francisco), Youjin Lee(University of California, San Francisco), Ryan Apathy(University of California, San Francisco), Mitchell J. Lipke(University of California, San Francisco), Jennifer A. Smith(University of California, San Francisco), Tina Zheng(University of California, San Francisco), Ian C. Boothby(University of California, San Francisco), Erin Isaza(QB3), Jackie Chan(University of California, San Francisco), Dante Acenas(University of California, San Francisco), Jinwoo Lee(University of California, San Francisco), Trisha A. Macrae(University of California, San Francisco), Than S. Kyaw(University of California, San Francisco), David Wu(University of California, San Francisco), Dianna Ng(University of California, San Francisco), Wei Gu(University of California, San Francisco), Vanessa A. York(University of California, San Francisco), Haig Alexander Eskandarian(University of California, San Francisco), Perri C. Callaway(University of California, San Francisco), Lakshmi Warrier(University of California, San Francisco), Mary E. Moreno(University of California, San Francisco), Justine Levan(University of California, San Francisco), Leonel Torres(University of California, San Francisco), Lila A. Farrington(University of California, San Francisco), Rita P. Loudermilk(University of California, San Francisco), Kanishka Koshal(University of California, San Francisco), Kelsey C. Zorn(University of California, San Francisco), Wilfredo F. García-Beltrán(Harvard University), Diane Yang(Harvard University), Michael G. Astudillo(Harvard University), B Bernstein(Harvard University), Jeffrey A. Gelfand(Harvard University), Edward T. Ryan(Harvard University), Richelle C. Charles(Harvard University), A. John Iafrate(Harvard University), Jochen K. Lennerz(Harvard University), Steve Miller(University of California, San Francisco), Charles Y. Chiu(University of California, San Francisco), Susan L. Stramer(American Red Cross), Michael R. Wilson(University of California, San Francisco), Aashish Manglik(University of California, San Francisco), Chun Ye(University of California, San Francisco), Nevan J. Krogan(Gladstone Institutes), Mark S. Anderson(University of California, San Francisco), Jason G. Cyster(Howard Hughes Medical Institute), J. Ernst(University of California, San Francisco), Alan H.B. Wu(University of California, San Francisco), Kara L. Lynch(University of California, San Francisco), Caryn Bern(University of California, San Francisco), Patrick D. Hsu(Innovative Genomics Institute), Alexander Marson(Gladstone Institutes)
medRxiv
April 29, 2020
10.1101/2020.04.25.20074856
Cited by 253Open Access
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Abstract

BACKGROUND: Serological tests are crucial tools for assessments of SARS-CoV-2 exposure, infection and potential immunity. Their appropriate use and interpretation require accurate assay performance data. METHOD: We conducted an evaluation of 10 lateral flow assays (LFAs) and two ELISAs to detect anti-SARS-CoV-2 antibodies. The specimen set comprised 128 plasma or serum samples from 79 symptomatic SARS-CoV-2 RT-PCR-positive individuals; 108 pre-COVID-19 negative controls; and 52 recent samples from individuals who underwent respiratory viral testing but were not diagnosed with Coronavirus Disease 2019 (COVID-19). Samples were blinded and LFA results were interpreted by two independent readers, using a standardized intensity scoring system. RESULTS: Among specimens from SARS-CoV-2 RT-PCR-positive individuals, the percent seropositive increased with time interval, peaking at 81.8-100.0% in samples taken >20 days after symptom onset. Test specificity ranged from 84.3-100.0% in pre-COVID-19 specimens. Specificity was higher when weak LFA bands were considered negative, but this decreased sensitivity. IgM detection was more variable than IgG, and detection was highest when IgM and IgG results were combined. Agreement between ELISAs and LFAs ranged from 75.7-94.8%. No consistent cross-reactivity was observed. CONCLUSION: Our evaluation showed heterogeneous assay performance. Reader training is key to reliable LFA performance, and can be tailored for survey goals. Informed use of serology will require evaluations covering the full spectrum of SARS-CoV-2 infections, from asymptomatic and mild infection to severe disease, and later convalescence. Well-designed studies to elucidate the mechanisms and serological correlates of protective immunity will be crucial to guide rational clinical and public health policies.

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