COVID-19 in patients with immune-mediated inflammatory diseases
Authors:   , Boekel Laura 
Published: January 2024

The COVID-19 pandemic raised major concerns for patients with immune-mediated inflammatory diseases (IMIDs), but simultaneously provided unique opportunities to investigate infection risk of IMID patients and effects of immunosuppressive treatment. At the Amsterdam Rheumatology and Immunology Center (ARC), we therefore set up a prospective cohort study to compare COVID-19 related outcomes between patients with rheumatic IMIDs and healthy controls. We designed a digital research platform that was complemented by serum collection via home finger pricks, in order to collect clinical and serological data remotely from over 3000 IMID patients and 1000 healthy controls. During the first six months of the pandemic, we observed that IMID patients were almost twice as likely to adhere to strict isolation measures compared to healthy controls, indicating that adherence to isolation measures would be an important factor to consider when interpreting incidence and hospitalization rates of SARS-CoV-2 infections. Subsequently, we were able to demonstrate that the risk of COVID-19 related hospitalization was comparable for IMID patients and healthy controls, except for patients treated with anti-CD20 therapy who showed a higher risk for developing severe COVID-19 manifestations. Near the end of 2020, it became clear that SARS-CoV-2 vaccinations would soon become available for the Dutch population, but this news was accompanied by hesitancy among people. We therefore investigated the perspective of IMID patients and healthy controls towards SARS-CoV-2 vaccination, and observed that vaccination willingness was similar for patients and controls. Hesitancy was mostly caused by concerns for adverse events, lack of long-term research and concerns for aggravation of underlying IMIDs, but this could for an important part be addressed by vaccine counseling by treating rheumatologists. As we had seen that concerns for adverse events were an important reason for hesitancy towards SARS-CoV-2 vaccinations among IMID patients, we investigated the occurrence of adverse events after first SARS-CoV-2 vaccinations early after the start of the Dutch vaccination program. Reassuringly, we showed that SARS-CoV-2 vaccines were well-tolerated by IMID patients. Next, we investigated effects of different immunosuppressants on antibody development after SARS-CoV-2, and found that methotrexate reduced seroconversion rates only after a first vaccine dose, whereas anti-CD20 therapy considerably impaired seroconversion rates after first and second vaccine doses. We therefore advocated that physicians should critically re-evaluate the necessity of anti-CD20 therapy with their patients. In 2021, the SARS-CoV-2 virus evolved into new variants of concern; the delta (B.1.617.2) and omicron (B.1.1.529) variant. For both variants, we compared the disease severity of infections between IMID patients and controls, and showed that the risk of severe disease was similar between both groups, again with the exception for patients treated with anti-CD20 therapy who remained at increased risk of hospitalization. Lastly, we compared the incidence and characteristics of long COVID between IMID patients and healthy controls during the omicron dominant period, while trying to account for shared symptoms between long COVID and rheumatic IMIDs. Our results indicate that while IMID patients were more likely to fulfill criteria for long COVID compared to controls, the observed difference could be partly explained by clinical manifestations in the context of underlying rheumatic diseases.
In conclusion, our combined use of a digital platform and finger pricks to longitudinally monitor a large cohort of IMID patients and healthy controls enabled us to answer important COVID-19 related questions in an efficient and innovative manner at a time when the need for information was extremely high. This allowed us to actively contribute to informing and reassuring IMID patients during the pandemic, and to successfully advocate for an early additional SARS-CoV-2 vaccination for all patients receiving anti-CD20 therapy and adaptation of treatment guidelines for rituximab in IMID patients.