Breakthrough SARS-CoV-2 infections with the delta (B.1.617.2) variant in immunosuppressed vaccinated individuals with immune-mediated inflammatory diseases: a substudy of two prospective cohort studies

Concerns have been raised about the likelihood of SARS-CoV-2 breakthrough infections in vaccinated patients with immune-mediated inflammatory disorders who are on immunosuppressants, although clinical evidence on these infections is currently lacking. The primary goal of this study was to compare the incidence and severity of SARS-CoV-2 breakthrough infections in patients with immune-mediated inflammatory diseases who were taking immunosuppressants versus controls (patients with immune-mediated inflammatory diseases who were not on immunosuppressants and healthy controls) who had received full COVID-19 vaccinations. The secondary goal was to look at the factors that lead to SARS-CoV-2 delta (B.1.617.2) breakthrough infections, as well as humoral immune responses following vaccination.

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Methods

We combined data from two major ongoing prospective multicenter cohort studies in the Netherlands (the Target to-B! [T2B!] project and the Amsterdam Rheumatology Center COVID [ARC-COVID] research) for this substudy. Adult patients with immune-mediated inflammatory disorders and healthy controls were included in both investigations. Clinical information was gathered using standardised electronic case record forms, digital questionnaires, and medical records. Only those who have been vaccinated against SARS-CoV-2 were included in the study. Participants for T2B! were recruited between February 2 and August 1, 2021, and for ARC-COVID, between April 26, 2020, and March 1, 2021. The data on breakthrough infections acquired between July 1 and December 15, 2021, when the delta SARS-CoV-2 variation was the prevalent form in the Netherlands, was analysed in this research. A SARS-CoV-2 breakthrough infection was defined as a SARS-CoV-2 infection verified by PCR or antigen test at least 14 days following immunisation. Due to the delta variant's dominance throughout the research period, all breakthrough infections were believed to be caused by it. Anti-receptor binding domain (RBD) antibodies were used to evaluate the humoral vaccination response (T2B! study alone) and anti-nucleocapsid antibodies were used to detect asymptomatic breakthrough infections in post-vaccination serum samples (ARC-COVID study only). We investigated possible clinical and humoral variables linked to the risk of breakthrough infections using multivariable logistic regression models. The T2B! study has been registered with the Dutch Trial Register under the number NL8900, while the ARC-COVID study has been registered under the number NL8513.

Findings

3207 individuals with immune-mediated inflammatory disorders who were using immunosuppressants and 1807 healthy people were included in the study (985 patients with immune-mediated inflammatory disease not on immunosuppressants and 822 healthy controls). Patients on immunosuppressants had a mean age of 53 years (SD 14), with 2042 (64 percent) of 3207 females and 1165 (36 percent) males; patients not on immunosuppressants had a mean age of 54 years (SD 14), with 598 (61 percent) of 985 females and 387 (39 percent) males; and healthy controls had a mean age of 57 years (SD 13), with 549 (67 percent) of 822 females and 2 Patients on immunosuppressants (148 of 3207; 46% [95 percent CI 39%–54%]), patients not on immunosuppressants (52 of 985; 53% [95 percent CI 40–69%]), and healthy controls (33 of 822; 40% [95 percent CI 28%–56%]) all had similar rates of PCR-test or antigen-test confirmed SARS-CoV-2 breakthrough infections. There was no change in the risk of breakthrough infection between immunosuppressant-treated patients with immune-mediated inflammatory illness and combined controls (ie, patients not on immunosuppressants and healthy controls; adjusted odds ratio 088 [95 percent CI 066–118]). Seroconversion after vaccination (odds ratio 058 [95 percent confidence interval 034–098]; T2B! cohort alone) and SARS-CoV-2 infection before vaccination (odds ratio 034 [018–056]) were linked to a decreased risk of breakthrough infections.