ABSTRACT
Background: Research on the disease severity of COVID-19 in patients with rheumatic immune-mediated inflammatory diseases (IMIDs) has been inconclusive, and long-term prospective data on the development of SARS-CoV-2 antibodies in these patients are lacking. We conducted an investigator-driven prospective cohort study to compare the disease severity of COVID-19, and the development of SARS-CoV-2 antibodies over time between patients with rheumatic IMIDs and healthy controls.Methods: Adult patients with rheumatic IMIDs from the Amsterdam Rheumatology & immunology Center, Amsterdam were invited to participate. All patients were asked to recruit their own sex- and age-matched control subject. We developed a new platform for collecting clinical data in large patient groups with online questionnaires (at baseline, and after 1-4 and 5-9 months of follow-up). Serum samples were collected two times during follow-up; after completing the follow-up questionnaires and prior to COVID-19 vaccination. All serum samples were analyzed for the presence of SARS-CoV-2 specific antibodies with a total-antibody bridging ELISA. IgG titers were quantified in samples with a positive test result in the bridging assay. Logistic regression analyses, and linear and logistic mixed model analyses were used to compare COVID-19 related hospitalization rates, proportions of SARS-CoV-2 seropositivity and IgG antibody titers between patients and controls, and between patients stratified for major immunosuppressive drug categories (i.e. biological [b] or conventional synthetic [cs] disease modifying anti-rheumatic drugs [DMARDs]).Findings: In total, 3080 consecutive patients and 1102 healthy controls with comparable age and sex distribution were included for analyses. The incidence of COVID-19 was slightly lower in patients compared to controls (14.7% vs. 16.0% had detectable SARS-CoV-2 antibodies), but patients were more frequently hospitalized compared to controls; 23 of 347 (7%) patients vs. 1 of 134 (0.7%) controls (adjusted OR: 7.33, 95% CI: 0.96 – 55.77, P 0.055). Three (13%) of 23 patients were admitted to the intensive care unit (ICU), and one of these died. Only treatment with B-cell targeting therapy was independently associated with an increased risk of COVID-19 related hospitalization (adjusted OR: 14.62, 95% CI: 2.31 – 92.39, P 0.004). Proportions of SARS-CoV-2 seropositivity in participants with a PCR confirmed COVID-19 diagnosis were similar for patients and controls ( P 0.73), and did not significantly decrease during the first twelve months after infection ( P 0.10). IgG antibody titers were higher in hospitalized patients compared to non-hospitalized patients, and slowly declined with time (rate per month: 0.86, 95% CI: 0.81 – 0.91, P < 0.0001) in similar patterns for patients in all treatment subgroups and controls.Interpretation: We observed that patients with rheumatic IMIDs, especially those treated with B-cell targeting therapy, were more likely to be hospitalized when infected with SARS-CoV-2, although subsequent ICU admissions and/or death were infrequent. In addition, treatment with cs- or bDMARDs other than B-cell targeting agents is unlikely to have negative effects on the development of long-lasting humoral immunity against SARS-CoV-2.Funding Information: ZonMw and Reade Foundation.Declaration of Interests: None to declare. Ethics Approval Statement: The research protocol was approved by the medical ethical committee of the VU University medical center (registration number 2020.169). All participants gave written informed consent.