Primary SARS-CoV-2 infection in patients with immune-mediated inflammatory diseases: long-term humoral immune responses and effects on disease activity
Authors: van Dam Koos P. J. , Volkers Adriaan G. , Wieske Luuk , Stalman Eileen W. , Kummer Laura Y. L. , van Kempen Zoé L. E. , Killestein Joep , Tas Sander W. , Boekel Laura , Wolbink Gerrit J. , van der Kooi Anneke J. , Raaphorst Joost , Takkenberg R. Bart , D’Haens Geert R. A. M. , Spuls Phyllis I. , Bekkenk Marcel W. , Musters Annelie H. , Post Nicoline F. , Bosma Angela L. , Hilhorst Marc L. , Vegting Yosta , Bemelman Frederike J. , Voskuyl Alexandre E. , Broens Bo , Sanchez Agner Parra , van Els Cécile A. C. M. , de Wit Jelle , Rutgers Abraham , de Leeuw Karina , Horváth Barbara , Verschuuren Jan J. G. M. , Ruiter Annabel M. , van Ouwerkerk Lotte , van der Woude Diane , Allaart Renée C. F. , Teng Y. K. Onno , van Paassen Pieter , Busch Matthias H. , Jallah Papay B. P. , Brusse Esther , van Doorn Pieter A. , Baars Adája E. , Hijnen Dirk Jan , Schreurs Corine R. G. , van der Pol W. Ludo , Goedee H. Stephan , Steenhuis Maurice , Keijzer Sofie , Keijser Jim B. D. , Cristianawati Olvi , ten Brinke Anja , Verstegen Niels J. M. , van Ham S. Marieke , Rispens Theo , Kuijpers Taco W. , Löwenberg Mark , Eftimov Filip ,   on behalf of the T2B! Immunity against SARS-CoV-2 study group
Published: May 2023

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.