Do quantitative levels of antispike‐IgG antibodies aid in predicting protection from SARS‐CoV‐2 infection? Results from a longitudinal study in a police cohort

In a COVID-19 sero-surveillance cohort study with predominantly healthy and vaccinated individuals, the objectives were (i) to investigate longitudinally the factors associated with the quantitative dynamics of antispike (anti-S1) IgG antibody levels, (ii) to evaluate whether the levels were associated with protection from SARS-CoV-2 infection, and (iii) to assess whether the association was different in the pre-Omicron compared with the Omicron period. The QuantiVac Euroimmun ELISA test was used to quantify anti-S1 IgG levels. The entire study period (16 months), the 11-month pre-Omicron period and the cross-sectional analysis before the Omicron surge included 3219, 2310, and 895 reactive serum samples from 949, 919, and 895 individuals, respectively. Mixed-effect linear, mixed-effect time-to-event, and logistic regression models were used to achieve the objectives. Age and time since infection or vaccination were the only factors associated with a decline of anti-S1 IgG levels. Higher antibody levels were significantly associated with protection from SARS-CoV-2 infection (0.89, 95% confidence interval [CI] 0.82-0.97), and the association was higher during the time period when Omicron was predominantly circulating compared with the ones when Alpha and Delta variants were predominant (adjusted hazard ratio for interaction 0.66, 95% CI 0.53-0.84). In a prediction model, it was estimated that >8000 BAU/mL anti-S1 IgG was required to reduce the risk of infection with Omicron variants by approximately 20%-30% for 90 days. Though, such high levels were only found in 1.9% of the samples before the Omicron surge, and they were not durable for 3 months. Anti-S1 IgG antibody levels are statistically associated with protection from SARS-CoV-2 infection. However, the prediction impact of the antibody level findings on infection protection is limited.

[1]  P. Sendi,et al.  The disease burden of Delta and Omicron variants of severe acute respiratory syndrome coronavirus 2 in a predominantly vaccinated and healthy cohort , 2022, Clinical Microbiology and Infection.

[2]  R. Biemann,et al.  Comparison of the measured values of quantitative SARS-CoV-2 spike antibody assays , 2022, Journal of Clinical Virology.

[3]  Kuan-Ying A. Huang,et al.  Overview of Neutralization Assays and International Standard for Detecting SARS-CoV-2 Neutralizing Antibody , 2022, Viruses.

[4]  A. Piwowar,et al.  How Humoral Response and Side Effects Depend on the Type of Vaccine and Past SARS-CoV-2 Infection , 2022, Vaccines.

[5]  D. Barouch,et al.  Neutralization Escape by SARS-CoV-2 Omicron Subvariants BA.2.12.1, BA.4, and BA.5 , 2022, The New England journal of medicine.

[6]  E. Theel,et al.  Serosurveillance after a COVID‐19 vaccine campaign in a Swiss police cohort , 2022, Immunity, inflammation and disease.

[7]  D. Harats,et al.  Efficacy of a Fourth Dose of Covid-19 mRNA Vaccine against Omicron , 2022, The New England journal of medicine.

[8]  R. Wölfel,et al.  Side-By-Side Evaluation of Three Commercial ELISAs for the Quantification of SARS-CoV-2 IgG Antibodies , 2022, Viruses.

[9]  Özge Uluçkan,et al.  Comparison of SARS-CoV-2 anti-spike receptor binding domain IgG antibody responses after CoronaVac, BNT162b2, ChAdOx1 COVID-19 vaccines, and a single booster dose: a prospective, longitudinal population-based study , 2022, The Lancet Microbe.

[10]  O. Levy,et al.  Waning effectiveness of SARS-CoV-2 mRNA vaccines in older adults: a rapid review , 2022, medRxiv.

[11]  T. Peto,et al.  Effect of Covid-19 Vaccination on Transmission of Alpha and Delta Variants , 2022, The New England journal of medicine.

[12]  E. Theel,et al.  A Multidimensional Cross-Sectional Analysis of Coronavirus Disease 2019 Seroprevalence Among a Police Officer Cohort: The PoliCOV-19 Study , 2021, Open forum infectious diseases.

[13]  O. Vandenberg,et al.  Neutralizing antibody responses following natural SARS-CoV-2 infection: Dynamics and correlation with commercial serologic tests. , 2021, Journal of Clinical Virology.

[14]  G. Hartmann,et al.  Correlation between a quantitative anti‐SARS‐CoV‐2 IgG ELISA and neutralization activity , 2021, Journal of medical virology.

[15]  P. Findeisen,et al.  Multicentre Performance Evaluation of the Elecsys Anti-SARS-CoV-2 Immunoassay as an Aid in Determining Previous Exposure to SARS-CoV-2 , 2021, Infectious Disease and Therapy.

[16]  A. Mangia,et al.  Early Serological Response to BNT162b2 mRNA Vaccine in Healthcare Workers , 2021, Vaccines.

[17]  E. Zeggini,et al.  In Search of the SARS-CoV-2 Protection Correlate: Head-to-Head Comparison of Two Quantitative S1 Assays in Pre-characterized Oligo-/Asymptomatic Patients , 2021, Infectious Diseases and Therapy.

[18]  M. Davenport,et al.  Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection , 2021, Nature Medicine.

[19]  R. Chemaly,et al.  How to interpret and use COVID-19 serology and immunology tests , 2021, Clinical Microbiology and Infection.

[20]  P. Findeisen,et al.  Performance evaluation of the Roche Elecsys Anti-SARS-CoV-2 S immunoassay , 2021, Journal of Virological Methods.

[21]  G. Rodger,et al.  Performance characteristics of five immunoassays for SARS-CoV-2: a head-to-head benchmark comparison , 2020, The Lancet Infectious Diseases.

[22]  D. Cummings,et al.  A systematic review of antibody mediated immunity to coronaviruses: kinetics, correlates of protection, and association with severity , 2020, Nature Communications.

[23]  D. Bhattacharya,et al.  Antibody Responses to SARS-CoV-2: Let’s Stick to Known Knowns , 2020, The Journal of Immunology.

[24]  OUP accepted manuscript , 2022, Rheumatology.