ABSTRACT
Variants of SARS-CoV-2 may evade natural and vaccine induced immunity and monoclonal antibody immunotherapeutics. There is an urgent need to know how well antibodies, induced by healthy and Clinically Extremely Vulnerable (CEV) patients, will bind and thus help reduce transmission and severity of infection from variants of concern (VOC). This study determines the cross-reactive binding of serum antibodies obtained prior to and 28 days after a third vaccination in three cohorts; a health care worker cohort who received three doses of Pfizer-BioNtech (PPP), a cohort of CEV patients received two doses of the AstraZeneca-ChAdOx1-nCoV-19 (AAP) vaccine, followed by a third PFZ vaccine and a haemodialysis cohort that had a mixture of two AZ or PFZ vaccines followed by a PFZ booster. Six months post second vaccine there was evidence of antibody waning with 58.9% of individuals in the HD cohort seropositive against Wuhan, 34.4% Delta and 62.2% Omicron strains. For the AAP cohort, equivalent figures were 62.5%, 45.8% and 91.7% and the PPP cohort 92.2%, 90% and 91.1%. Post third dose vaccination there were universal increases in seropositivity and median optical density. For the HD cohort, 98.8% were seropositive to the Wuhan strain, 97.6% against Delta and 100% against Omicron strains. For the PPP and AAP cohorts, 100% were seropositive against all 3 strains. Lastly, we examined the WHO NIBSC 20/136 standard and there was no loss of antibody binding to either VOC. Similarly, a dilution series of Sotrovimab (GSK) found this therapeutic monoclonal antibody bound similarly to all VOC.
Subject(s)
Huntington DiseaseABSTRACT
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.