Intensity and longevity of SARS-CoV-2 vaccination response in patients with immune-mediated inflammatory disease: a prospective cohort study

Abstract

Background: Concerns have been raised about the reduced immunogenicity of vaccines against SARS-CoV-2 in patients with immune-mediated inflammatory diseases and the higher risk of breakthrough infections. The objective of our study was to investigate the intensity and longevity of SARS-CoV-2 vaccination responses in patients with immune-mediated inflammatory diseases, and to assess the effects of diagnosis, treatment, and adapted vaccination schedules.

Methods: SARS-CoV-2 IgG antibody response after SARS-CoV-2 vaccination was measured over time in a large prospective cohort of healthy controls and participants with immune-mediated inflammatory diseases (attending or admitted to affiliated centres) between Dec 15, 2020, and Dec 1, 2021. Cohort participants with immune-mediated inflammatory diseases and control participants with no diagnosis of immune-mediated inflammatory diseases, were eligible for this analysis. Demographic data and disease-specific data were collected using a questionnaire. Humoral response was compared across treatment and disease groups, and with respect to the receipt of additional vaccinations. SARS-CoV-2 antibody response was measured by ELISA using optical density ratio units and modelled over time with age and sex adjustment using mixed-effects models. Using these models, marginal mean antibody titres and marginal risks of a poor response (optical density ratio <1·1) were calculated for each week starting from week 8 after the first vaccination to week 40.

Findings: Among 5076 individuals registered, 2535 participants with immune-mediated inflammatory diseases (mean age 55·0 [15·2] years; 1494 [58·9%] women and 1041 [41·1%] men) and 1198 healthy controls (mean age 40·7 [13·5] years; 554 [46·2%] women and 644 [53·8%] men) were included in this analysis. Mean antibody titres were higher in healthy controls compared with people with immune-mediated inflammatory diseases at all timepoints, with a peak antibody response in healthy controls (mean optical density ratio 12·48; 95% CI 11·50-13·53) of more than twice that in participants with immune-mediated inflammatory diseases (5·50; 5·23-5·77; mean difference 6·98; 5·92-8·04). A poor response to vaccination was observed in participants with immune-mediated inflammatory diseases who were taking B-cell inhibitors (peak mean difference from healthy controls 11·68; 10·07-13·29) and T-cell inhibitors (peakmean difference from healthy controls 10·43; 8·33-12·53). Mean differences in antibody responses between different immune-mediated inflammatory diseases were small. Participants with immune-mediated inflammatory diseases who were given a third vaccine dose had higher mean antibody titres than did healthy controls vaccinated with two vaccine doses at 40 weeks after the initial vaccination (mean difference 1·34; 0·01-2·69).

Interpretation: People with immune-mediated inflammatory diseases show a lower and less durable SARS-CoV-2 vaccination response and are at risk of losing humoral immune protection. Adjusted vaccination schedules with earlier booster doses or more frequent re-doses, or both, could better protect people with immune-mediated inflammatory diseases.

Funding: Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, European Research Council, Innovative Medicine Initiative, Friedrich-Alexander-Universität Erlangen-Nürnberg, Else Kröner-Memorial Foundation.

Figure 1

Estimated marginal mean anti-spike IgG titres (A) and estimated risks of a poor antibody response (B) between 8 to 40 weeks after first vaccination The bands represent the 95% CIs. The dashed lines mark negative (0·8) and borderline (1·1) optical density ratio thresholds. Estimated risk of poor response is the estimated percentage of participants that would have a poor vaccine response at a given timepoint on the x axis.

Figure 2

Age-adjusted and sex-adjusted estimated marginal mean anti-spike IgG titres at 8–40 weeks after first vaccination by immune-mediated inflammatory disease diagnosis The bands represent the 95% CIs. The panels are ordered by peak mean value from highest to lowest. The dashed lines mark negative (0·8) and borderline (1·1) optical density ratio thresholds.

Figure 3

Age-adjusted and sex-adjusted estimated marginal mean anti-spike IgG titres at 8–40 weeks after first vaccination by type of treatments used for immune-mediated inflammatory diseases The bands represent the 95% CIs. The panels are ordered by the mean of the estimated mean values at all timepoints from highest to lowest. The dashed lines mark negative (0·8) and borderline (1·1) optical density ratio thresholds. A list of individual drugs per class are provided in the appendix (p 1).

Figure 4

Age-adjusted and sex-adjusted estimated marginal mean anti-spike antibody titres in healthy controls and participants with immune-mediated inflammatory diseases receiving two or three doses of COVID-19 vaccine The bands represent the 95% CIs. The grey dashed lines at the bottom mark negative (0·8) and borderline (1·1) optical density ratio thresholds.