Primary SARS-CoV-2 infection in patients with immune-mediated inflammatory diseases: long-term humoral immune responses and effects on disease activity

Abstract

Background Patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressants (ISPs) may have impaired long-term humoral immune responses and increased disease activity after SARS-CoV-2 infection. We aimed to investigate long-term humoral immune responses against SARS-CoV-2 and increased disease activity after a primary SARS-CoV-2 infection in unvaccinated IMID patients on ISPs. Methods IMID patients on active treatment with ISPs and controls (i.e. IMID patients not on ISP and healthy controls) with a confirmed SARS-CoV-2 infection before first vaccination were included from an ongoing prospective cohort study (T2B! study). Clinical data on infections and increased disease activity were registered using electronic surveys and health records. A serum sample was collected before first vaccination to measure SARS-CoV-2 anti-receptor-binding domain (RBD) antibodies. Results In total, 193 IMID patients on ISP and 113 controls were included. Serum samples from 185 participants were available, with a median time of 173 days between infection and sample collection. The rate of seropositive IMID patients on ISPs was 78% compared to 100% in controls (p < 0.001). Seropositivity rates were lowest in patients on anti-CD20 (40.0%) and anti-tumor necrosis factor (TNF) agents (60.5%), as compared to other ISPs (p < 0.001 and p < 0.001, respectively). Increased disease activity after infection was reported by 68 of 260 patients (26.2%; 95% CI 21.2–31.8%), leading to ISP intensification in 6 out of these 68 patients (8.8%). Conclusion IMID patients using ISPs showed reduced long-term humoral immune responses after primary SARS-CoV-2 infection, which was mainly attributed to treatment with anti-CD20 and anti-TNF agents. Increased disease activity after SARS-CoV-2 infection was reported commonly, but was mostly mild. Trial registration NL74974.018.20, Trial ID: NL8900. Registered on 9 September 2020.

The risk of COVID-19 in IBD patients is increased by urban living and is not influenced by disease activity or intravenous biologics

“…Indeed, in this study, anti-SARS-CoV-2 antibodies were only assessed at the end of the follow-up for all patients, and in patients who were seropositive at the time of their last infusion, anti-SARS-CoV-2 antibody assays were retrospectively performed at each of their visit in order to determine the time of seroconversion. Thus, we may have underestimated the number of pauci-symptomatic infections if they were contracted early during the follow-up, particularly for patients treated with anti-TNF, that can attenuate seroprevalence as suggested in some studies ( 43 , 44 ), even though another study recently showed that patients with IBD previously infected with COVID-19 have similar quantitative antibody response as healthy controls previously infected with COVID-19 ( 45 ). The parallel can be drawn with the response to the vaccination because the antibody levels after vaccination have been shown to be lower with anti-TNF agents than with other treatments, studied in this prospective case-control study (483 cases for 121 controls) between May and November 2021, in which the antibody level measured between 53 and 92 days after the second vaccination dose was lower under infliximab (geometric mean ratio 0.12, 95% CI 0.08-0.17; p<0.0001), compared to thiopurines (0.89, 0.64-1.24; p=0.50), ustekinumab (0.69, 0.41-1.19; p=0.18), or vedolizumab (1.16, 0.74-1.83; p=0.51) ( 32 ).…”