Laboratory evaluation of SARS-CoV-2 antibodies: detectable IgG up to 20 weeks post infection

Abstract

Background The SARS-CoV-2 pandemic necessitated rapid and global responses across all areas of healthcare, including an unprecedented interest in serological immunoassays to detect antibodies to the virus. The dynamics of the immune response to SARS-CoV-2 is still not well understood. Methods We measure SARS-CoV-2 antibody levels in plasma samples from 880 people in Northern Ireland by Roche Elecsys Anti-SARS-CoV-2 IgG/IgA/IgM, Abbott SARS-CoV-2 IgG and EuroImmun IgG SARS-CoV-2 ELISA immunoassays to analyse immune dynamics over time. Using these results, we develop a "pseudo gold standard" reference cohort against which to assess immunoassay performance. We report performance metrics for the UK-RTC AbC-19 rapid lateral flow immunoassay (LFIA) against a characterised panel of 304 positives established using the "pseudo gold standard" system and 350 negative samples. Results We detect persistence of SARS-CoV-2 IgG up to 140 days (20 weeks) post infection, across all three antibody immunoassays, at levels up to 4.4 times the cut-off for a positive result by Roche measurement. Using our "pseudo gold standard" cohort (n=348 positive, n=510 negative) we determine the sensitivity and specificity of the three commercial immunoassays used (EuroImmun; Sens. 98.9% [97.7-99.7%]; Spec. 99.2% [98.4-99.8%]; Roche; Sens. 99.4% [98.6-100%]; Spec. (96.7% [95.1-98.2%]; Abbott; Sens. 86.8% [83.1-90.2%]; Spec. (99.2% [98.4-99.8%]). The UK-RTC AbC-19 lateral flow immunoassay using shows a sensitivity of 97.70% (95.72%-99.34%) and specificity of 100% (100.00-100.00%). Conclusions Through comprehensive analysis of a large cohort of pre-pandemic and pandemic individuals, we show detectable levels of IgG antibodies, lasting up to 140 days, providing insight to immunity levels at later time points. We propose an alternative to RT-PCR positive status as a standard for assessing SARS-CoV-2 antibody assays and show strong performance metrics for the AbC-19 rapid test.

Covid-19: Government buried negative data on its favoured antibody test

“…The study findings contrast with those of an earlier study2—published as a preprint and not yet peer reviewed, which was funded by some of the consortium developing and producing the test—that suggested that the test gave no false positive results.…”

Evaluation of Antibody Response in Symptomatic and Asymptomatic COVID-19 Patients and Diagnostic Assessment of New IgM/IgG ELISA Kits

“…The early IgG response is possibly a memory response from earlier coronavirus infection, producing cross-reactive antibodies that do not have neutralizing potency [52]. This was observed in several infections with closely related viruses, where some caused antibody-dependent enhancement (ADE) disease, leading to a worse clinical course [52,54]. In addition, this could explain why the symptomatic patients had a higher IgG detection rate than the asymptomatic patients.…”

“…This could be due to several reasons, including false-positive RT-PCR test, reactive RT-PCR with high CT value, an early-stage infection, a transient antibody response, no production of an antibody response, or production of antibodies that are below the detection level of the assays [36,37,39,48]. Some studies have indicated similar findings where they failed to detect a SARS-CoV-2 antibody response in variable portions of their COVID-19 sample cohorts [54][55][56].…”

Potential Spreading Dynamics of COVID-19 with Temporary Immunity – A Mathematical Modeling Study

“…al. (2020) have very recently reported an antibody half-life of 85 days and a median time of 137 days to loss of positivity; these results are corrborated by Robertson et. al.…”