Serological surveillance of SARS-CoV-2: Six-month trends and antibody response in a cohort of public health workers

Abstract

Background: Antibody waning after SARS-CoV-2 infection may result in reduction in long-term immunity following natural infection and vaccination, and is therefore a major public health issue. We undertook prospective serosurveillance in a large cohort of healthy adults from the start of the epidemic in England.

Methods: Clinical and non-clinical healthcare workers were recruited across three English regions and tested monthly from March to November 2020 for SARS-CoV-2 spike (S) protein and nucleoprotein (N) antibodies using five different immunoassays. In positive individuals, antibody responses and long-term trends were modelled using mixed effects regression.

Findings: In total, 2246 individuals attended 12,247 visits and 264 were seropositive in ≥ 2 assays. Most seroconversions occurred between March and April 2020. The assays showed > 85% agreement for ever-positivity, although this changed markedly over time. Antibodies were detected earlier with Abbott (N) but declined rapidly thereafter. With the EuroImmun (S) and receptor-binding domain (RBD) assays, responses increased for 4 weeks then fell until week 12-16 before stabilising. For Roche (N), responses increased until 8 weeks, stabilised, then declined, but most remained above the positive threshold. For Roche (S), responses continued to climb over the full 24 weeks, with no sero-reversions. Predicted proportions sero-reverting after 52 weeks were 100% for Abbott, 59% (95% credible interval 50-68%) Euroimmun, 41% (30-52%) RBD, 10% (8-14%) Roche (N) < 2% Roche (S).

Interpretation: Trends in SARS-CoV-2 antibodies following infection are highly dependent on the assay used. Ongoing serosurveillance using multiple assays is critical for monitoring the course and long-term progression of SARS-CoV-2 antibodies.

Fig. 1

% positive (spike protein IgG) or % positive/indeterminate (nucleoprotein IgG), by assay, study site and calendar month, with binomial 95% confidence intervals. Sample sizes are indicated above each bar. Note: There were 21 Roche N/S tests for Wythenshawe in October with majority positive, which are not shown. The high observed prevalence is likely due to sampling of particular individuals: 260 were sampled in September.

Fig. 2

Trends in antibody response in confirmed positives (at least two of EuroImmun, Roche N and Abbott). Means and bars for 95% confidence intervals are superimposed on the plot. Reference lines on the y-axis indicate positive threshold for the tests, the reference line at week 0 indicates time of first positive test (any assay).

Fig. 3

Kappa statistics with 95% confidence intervals for agreement between assays over the study period.