SARS-CoV-2 vaccination responses in untreated, conventionally treated and anticytokine-treated patients with immune-mediated inflammatory diseases

Abstract

Objectives: To better understand the factors that influence the humoral immune response to vaccination against SARS-CoV-2 in patients with immune-mediated inflammatory diseases (IMIDs).

Methods: Patients and controls from a large COVID-19 study, with (1) no previous history of COVID-19, (2) negative baseline anti-SARS-CoV-2 IgG test and (3) SARS-CoV-2 vaccination at least 10 days before serum collection were measured for anti-SARS-CoV-2 IgG. Demographic, disease-specific and vaccination-specific data were recorded.

Results: Vaccination responses from 84 patients with IMID and 182 controls were analysed. While all controls developed anti-SARS-CoV-2 IgG, five patients with IMID failed to develop a response (p=0.003). Moreover, 99.5% of controls but only 90.5% of patients with IMID developed neutralising antibody activity (p=0.0008). Overall responses were delayed and reduced in patients (mean (SD): 6.47 (3.14)) compared with controls (9.36 (1.85); p<0.001). Estimated marginal means (95% CI) adjusted for age, sex and time from first vaccination to sampling were 8.48 (8.12-8.85) for controls and 6.90 (6.45-7.35) for IMIDs. Significantly reduced vaccination responses pertained to untreated, conventionally and anticytokine treated patients with IMID.

Conclusions: Immune responses against the SARS-CoV-2 are delayed and reduced in patients with IMID. This effect is based on the disease itself rather than concomitant treatment.

Keywords: COVID-19; biological therapy; epidemiology; vaccination.

Figure 1

Temporal pattern of vaccination response and antibody levels in different disease and treatment groups. (A) Temporal course of anti-SARS-CoV-2 antibody formation after first and second mRNA vaccine doses, first vaccination is depicted by a dotted vertical line, second vaccination by a red vertical band, smoothed plots show time-conditional mean antibody levels in healthy controls and IMID subgroups. (B) Distribution of antibody levels by type of treatment (B) and diagnosis (C). Dotted horizontal lines represent OD cut-off of ≥0.8 (OD 450 nm). (D, E) Distribution of neutralisation activity of the antibodies based on per cent inhibition of binding of the receptor-binding domain to angiotensin-converting enzyme-2 by type of treatment (D) and diagnosis (E). Dotted horizontal lines represent cut-off of ≥30% inhibition. bDMARDs, biological disease-modifying antirheumatic drugs; csDMARDs, conventional synthetic disease-modifying antirheumatic drugs; IBD, inflammatory bowel disease; OD, optical density; PsA, psoriatic arthritis; RA, rheumatoid arthritis; SpA, spondyloarthritis; tsDMARDs, targeted-synthetic disease-modifying antirheumatic drugs.