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Determinants of SARS-CoV-2 IgG response and decay in Canadian healthcare workers: A prospective cohort study
Nicola Cherry1, Anil Adisesh2, Igor Burstyn3
1Division of Preventive Medicine, University of Alberta, 5-22 University Terrace, Edmonton, AB T6G 2T4, Canada.
Insights
This study tracked anti-receptor binding domain (anti-RBD) IgG in healthcare workers, finding that vaccine effectiveness wanes over time but is boosted by infection. Certain medical conditions and treatments lower antibody levels.
Area of Science:
- Immunology
- Infectious Diseases
- Public Health
Background:
- Healthcare workers (HCWs) provided serial blood samples to identify factors influencing anti-receptor binding domain (anti-RBD) IgG response to SARS-CoV-2.
- Understanding these factors is crucial for optimizing vaccination strategies and public health interventions.
Purpose of the Study:
- To identify factors associated with the anti-receptor binding domain (anti-RBD) IgG response to SARS-CoV-2 in a Canadian healthcare worker cohort.
- To analyze the longitudinal changes in anti-RBD IgG titers following vaccination and infection.
Main Methods:
- A prospective cohort of 2752 healthcare workers donated blood samples at multiple time points post-vaccination (4, 7, 10, 13 months).
- Data on immunizations, SARS-CoV-2 infections, and medical conditions were collected.
- Anti-RBD IgG and anti-nucleocapsid IgG levels were measured centrally; statistical modeling was used to analyze the data, including sensitivity analyses for self-report bias.
Main Results:
- Anti-RBD IgG titers increased with vaccine doses and infection but decreased over time, with the sharpest decline after the third dose.
- mRNA-1273 (Moderna) immunization resulted in higher anti-RBD IgG.
- Lower IgG titers were observed in individuals with multiple sclerosis, rheumatoid arthritis, or on specific immunosuppressive therapies. Lower titers were also noted in women immunized during early or mid-pregnancy.
Conclusions:
- Prospective cohort design and serial serology assessments enhanced the accuracy of findings.
- Longitudinal analysis provided a clearer understanding of factors affecting vaccine response, including medical conditions and treatment regimens.
Introduction:
Healthcare workers (HCWs) from an interprovincial Canadian cohort gave serial blood samples to identify factors associated with anti-receptor binding domain (anti-RBD) IgG response to the SARS-CoV-2 virus.
Methods:
Members of the HCW cohort donated blood samples four months after their first SARS-CoV-2 immunization and again at 7, 10 and 13 months. Date and type of immunizations and dates of SARS-CoV-2 infection were collected at each of four contacts, together with information on immunologically-compromising conditions and current therapies. Blood samples were analyzed centrally for anti-RBD IgG and anti-nucleocapsid IgG (Abbott Architect, Abbott Diagnostics). Records of immunization and SARS-CoV-2 testing from public health agencies were used to assess the impact of reporting errors on estimates from the random-effects multivariable model fitted to the data.
Results:
2752 of 4567 vaccinated cohort participants agreed to donate at least one blood sample. Modelling of anti-RBD IgG titer from 8903 samples showed an increase in IgG with each vaccine dose and with first infection. A decrease in IgG titer was found with the number of months since vaccination or infection, with the sharpest decline after the third dose. An immunization regime that included mRNA1273 (Moderna) resulted in higher anti-RBD IgG. Participants reporting multiple sclerosis, rheumatoid arthritis or taking selective immunosuppressants, tumor necrosis factor inhibitors, calcineurin inhibitors and antineoplastic agents had lower anti-RBD IgG. Supplementary analyses showed higher anti-RBD IgG in those reporting side-effects of vaccination, no relation of anti-RBD IgG to obesity and lower titers in women immunized in early or mid-pregnancy. Sensitivity analysis results suggested no important bias in the self-report data.
Conclusion:
Creation of a prospective cohort was central to the credibility of results presented here. Serial serology assessments, with longitudinal analysis, provided effect estimates with enhanced accuracy and a clearer understanding of medical and other factors affecting response to vaccination.
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