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

Ross J Harris¹, Heather J Whitaker¹, Nick J Andrews¹, Felicity Aiano², Zahin Amin-Chowdhury², Jessica Flood², Ray Borrow³, Ezra Linley³, Shazaad Ahmad⁴, Lorraine Stapley⁵, Bassam Hallis⁵, Gayatri Amirthalingam², Katja Höschler⁶, Ben Parker⁷, Alex Horsley⁸, Timothy J G Brooks⁹, Kevin E Brown², Mary E Ramsay², Shamez N Ladhani¹⁰

Affiliations

¹ Statistics, Modelling and Economics Department, Public Health England Colindale, National Infection Service, 61 Colindale Avenue, London NW9 5EQ, UK.
² Immunisation and Countermeasures Division, PHE Colindale, National Infection Service, 61 Colindale Avenue, London NW9 5EQ, UK.
³ Sero-epidemiology Unit, Public Health England, Public Health Laboratory Manchester, Manchester Medical Microbiology Partnership, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK.
⁴ Manchester University NHS Foundation Trust, UK.
⁵ Immunoassay Lab, National Infection Service, Porton Down, SP4 0JG, UK.
⁶ Virus Reference Department, Reference Microbiology, Public Health England Colindale, National Infection Service, 61 Colindale Avenue, London NW9 5EQ, UK.
⁷ NIHR Manchester Clinical Research Facility, Manchester University NHS Foundation Trust, Manchester M13 9WL, UK; Kellgren Centre for Rheumatology, NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester M13 9WL, UK.
⁸ Division of Infection, Inflammation and Respiratory Medicine, University of Manchester, Manchester M23 9LT, UK.
⁹ Rare & Imported Pathogens Laboratory, Public Health England, Manor Farm Road, Porton Down, Salisbury SO4 0JG, UK.
¹⁰ Immunisation and Countermeasures Division, PHE Colindale, National Infection Service, 61 Colindale Avenue, London NW9 5EQ, UK; Paediatric Infectious Diseases Research Group (PIDRG), St. Georges University of London (SGUL), London, UK. Electronic address: Shamez.Ladhani@phe.gov.uk.

PMID: 33766553
PMCID: PMC7982645
DOI: 10.1016/j.jinf.2021.03.015

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

Ross J Harris et al. J Infect. 2021 May.

. 2021 May;82(5):162-169.

doi: 10.1016/j.jinf.2021.03.015. Epub 2021 Mar 22.

Authors

Affiliations

¹ Statistics, Modelling and Economics Department, Public Health England Colindale, National Infection Service, 61 Colindale Avenue, London NW9 5EQ, UK.
² Immunisation and Countermeasures Division, PHE Colindale, National Infection Service, 61 Colindale Avenue, London NW9 5EQ, UK.
³ Sero-epidemiology Unit, Public Health England, Public Health Laboratory Manchester, Manchester Medical Microbiology Partnership, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, UK.
⁴ Manchester University NHS Foundation Trust, UK.
⁵ Immunoassay Lab, National Infection Service, Porton Down, SP4 0JG, UK.
⁶ Virus Reference Department, Reference Microbiology, Public Health England Colindale, National Infection Service, 61 Colindale Avenue, London NW9 5EQ, UK.
⁷ NIHR Manchester Clinical Research Facility, Manchester University NHS Foundation Trust, Manchester M13 9WL, UK; Kellgren Centre for Rheumatology, NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester M13 9WL, UK.
⁸ Division of Infection, Inflammation and Respiratory Medicine, University of Manchester, Manchester M23 9LT, UK.
⁹ Rare & Imported Pathogens Laboratory, Public Health England, Manor Farm Road, Porton Down, Salisbury SO4 0JG, UK.
¹⁰ Immunisation and Countermeasures Division, PHE Colindale, National Infection Service, 61 Colindale Avenue, London NW9 5EQ, UK; Paediatric Infectious Diseases Research Group (PIDRG), St. Georges University of London (SGUL), London, UK. Electronic address: Shamez.Ladhani@phe.gov.uk.

PMID: 33766553
PMCID: PMC7982645
DOI: 10.1016/j.jinf.2021.03.015

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.

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Figures

**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.

See this image and copyright information in PMC

Comment in

Reactogenicity, safety and antibody response, after one and two doses of mRNA-1273 in seronegative and seropositive healthcare workers.
Tré-Hardy M, Cupaiolo R, Papleux E, Wilmet A, Horeanga A, Antoine-Moussiaux T, Della Vecchia A, Beukinga I, Vekemans M, Blairon L. Tré-Hardy M, et al. J Infect. 2021 Aug;83(2):237-279. doi: 10.1016/j.jinf.2021.03.025. Epub 2021 Apr 1. J Infect. 2021. PMID: 33811939 Free PMC article. No abstract available.
One-year durability of anti-spike IgG to SARS-CoV-2: Preliminary data from the anticrown prospective observational study one year durability of COVID-19 anti-spike IgG.
Capetti AF, Borgonovo F, Mileto D, Gagliardi G, Mariani C, Lupo A, Dedivitiis G, Meraviglia P, Pellicciotta M, Armiento L, Cossu MV, Rizzardini G. Capetti AF, et al. J Infect. 2021 Aug;83(2):237-279. doi: 10.1016/j.jinf.2021.05.023. Epub 2021 May 27. J Infect. 2021. PMID: 34052240 Free PMC article.
Decreasing humoral response among healthcare workers up to 4 months after two doses of BNT162b2 vaccine.
Ferré VM, Lebourgeois S, Menidjel R, Collin G, Chenane HR, Guindi MO, Yazdanpanah Y, Timsit JF, Charpentier C, Descamps D, Fidouh N, Visseaux B. Ferré VM, et al. J Infect. 2022 Feb;84(2):248-288. doi: 10.1016/j.jinf.2021.09.017. Epub 2021 Sep 29. J Infect. 2022. PMID: 34600020 Free PMC article. No abstract available.

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

Affiliations

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

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References

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Medical

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