SARS-CoV-2 breakthrough infections in patients with immune-mediated inflammatory diseases

The SARS-CoV-2 pandemic has caused nearly 7,000,000 deaths globally. The Target-to-B! COVID-19 study, a multicentre cohort study, examined SARS-CoV-2 vaccine efficacy in immune-mediated inflammatory disease (IMID) patients treated with immunosuppressants. Compared to IMID patients without immunosuppressants and healthy individuals, patients treated with specific immunosuppressants showed impaired humoral responses. Suggesting reduced vaccine efficacy and thereby reduced protection against SARS-CoV-2 breakthrough infections.
We demonstrate that the occurrence and severity of SARS-CoV-2 breakthrough infections were similar among IMID patients treated with most immunosuppressants and healthy individuals. Patients using anti-CD20 therapy and S1P modulators, which greatly impair humoral responses had slightly increased incidence of SARS-CoV-2 breakthrough infections. However, severe cases were uncommon and often associated with additional risk factors for severe infections, such as older age and comorbidities. Protective factors against SARS-CoV-2 breakthrough infections included extra SARS-CoV-2 vaccinations and hybrid immunity, underlining the importance of repeated exposure to the viral antigen for clinical protection against SARS-CoV-2 infections. Increased disease activity of the underlying IMID due to SARS-CoV-2 (breakthrough) infections were usually self-limiting, resulting in temporary medication intensification in only a few cases. Overall, these results provide reassurance for IMID patients on immunosuppressants and underline the importance of repeated SARS-CoV-2 vaccinations in patients at risk for severe (SARSCoV-2) infections.