SARS-CoV-2 serology: Validation of high-throughput chemiluminescent immunoassay (CLIA) platforms and a field study in British Columbia

Abstract

Background SARS-CoV-2 antibody testing is required for estimating population seroprevalence and vaccine response studies. It may also increase case identification when as an adjunct to routine molecular testing. We performed a validation study and evaluated the use of automated high-throughput assays in a field study of COVID-19-affected care facilities. Methods Six automated assays were assessed: 1) DiaSorin LIAISON TM SARS-CoV-2 S1/S2 IgG; 2) Abbott ARCHITECT TM SARS-CoV-2 IgG; 3) Ortho VITROS TM Anti-SARS-CoV-2 Total; 4) VITROS TM Anti-SARS-CoV-2 IgG; 5) Siemens SARS-CoV-2 Total Assay; and 6) Roche Elecsys TM Anti-SARS-CoV-2. The validation study included 107 samples (42 known positive; 65 presumed negative). The field study included 296 samples (92 PCR positive; 204 PCR negative or not PCR tested). All samples were tested by the six assays. Results; All assays had sensitivities >90% in the field study, while in the validation study, 5/6 assays were >90% sensitive and DiaSorin was 79% sensitive. Specificities and negative predictive values were >95% for all assays. Field study estimated positive predictive values at 1%-10% disease prevalence were 100% for Siemens, Abbott and Roche, while DiaSorin and Ortho assays had lower PPVs at 1% prevalence, but PPVs increased at 5%-10% prevalence. In the field study, addition of serology increased diagnoses by 16% compared to PCR testing alone. Conclusions All assays evaluated in this study demonstrated high sensitivity and specificity for samples collected at least 14 days post-symptom onset, while sensitivity was variable 0-14 days after infection. The addition of serology to the outbreak investigations increased case detection by 16%.

Serial cross-sectional estimation of vaccine and infection-induced SARS-CoV-2 sero-prevalence in children and adults, British Columbia, Canada: March 2020 to August 2022

“…Prevalence log-odds were modeled for each snapshot independently, incorporating a hierarchical distribution for each age group, sex, and HA cell. High sensitivity and specificity have been reported for each of the CLIAs [15,16,22,25], but evaluations have not typically addressed potential variation by vaccination status, time since exposure, severity, age and/or target group [26][27][28]. Similar to other public health agencies [29,30], we do not adjust for sensitivity or specificity in primary analyses, but explore their effects as detailed in Supplementary_Material_2.…”

A systematic review and meta-analysis comparing the diagnostic accuracy tests of COVID-19

“…Five studies were selected using CLIA as an IgM detection technique [77,79,103,104,106]. A total of 1,240 subjects were studied.…”

All hands on deck: A multidisciplinary approach to SARS-CoV-2-associated MIS-C

“…BC’s case definition derived from the World Health Organization ( 2 ) was adapted to only include hospitalized cases and made available to the public through the BCCDC website on June 10, 2020 and to physicians through the College of Physicians and Surgeons of BC on August 28, 2020 ( 5 ). Serology testing was performed using the Ortho T VITROS Anti-SARS-CoV-2 Total antibody assay (Ortho IgG; Ortho Clinical Diagnostics, Rochester, NY), a Health Canada and FDA-licensed qualitative assay which detects IgA, IgG, and IgM antibodies ( 6 ).…”