Verification of a novel quantitative SARS-CoV-2 IgG immunomethod, and its use in the evaluation of the immune response following vaccination in healthcare workers

Introduction: The novel quantitative SARS-CoV-2 anti-spike IgG method from Abbott was fully evaluated in terms of imprecision, Limit of Detection, Limit of Quantitation, linearity, sensitivity, and specificity. The method was then used in the CALM (COVID-19 antibody longitudinal monitoring) observational cohort study performed at the Norfolk and Norwich University Hospital, which aimed to evaluate the immune response to SARS-CoV-2 vaccination in a real world setting. Methodology: The Abbott SARS-CoV-2 anti-spike IgG method is an automated two-step chemiluminescent microparticle immunomethod used for the quantitative determination of antibodies to the receptor binding domain of the S1 subunit. 107 healthcare workers were recruited to the CALM study and their antibody concentrations measured at baseline and weekly following vaccination with the SARS-CoV-2 (Pfizer/BioNTech) vaccine. Results: The SARS-CoV-2 anti-spike IgG method performed well, with excellent imprecision (≤3.9% in the positive range), sensitivity (98.3% [90.6-100.0]), and specificity (99.4% [97.1-100.0]). It was capable of measuring the immune response to natural infection from a range of SARS-CoV-2 strains, and to vaccination. The CALM study showed 98% of participants developed an antibody response following dose one of the vaccine, and 100% following dose two. For individuals responding to dose one, antibody concentrations peaked three weeks following vaccination, with concentrations remaining detectable ten weeks later prior to the second dose. Antibodies then remained detectable in all participants for six months following both doses. Spearman's correlation showed age had a significant effect on peak SARS-CoV-2 anti-spike IgG concentrations (p=0.015), with participants under 40 years of age having a greater antibody response to both doses of the SARS-CoV-2 (Pfizer/BioNTech) vaccine. Participants with a negative baseline result showed a 10-fold greater response to each vaccine dose than those with a positive baseline result (p=0.015). Discussion: Use of a quantitative SARS-CoV-2 anti-spike IgG method allows antibody development, peak concentration, and antibody decline over time to be evaluated. The CALM study identified a potential benefit from measuring SARS-CoV-2 anti-spike IgG antibodies three weeks following dose one of the vaccine to offer individuals not responding, an earlier second dose. The results support the UK government's decision to delay the dose interval, and allow more individuals to be vaccinated with one dose. They also suggest booster vaccines are not required until at least six months post second dose.