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

the T2B! Immunity against SARS-CoV-2 study group, Koos P.J. van Dam, Adriaan G. Volkers, the T2B! Immunity against SARS-CoV-2 study group, Luuk Wieske, Eileen W. Stalman, Laura Y.L. Kummer, Zoé L.E. van Kempen, Joep Killestein, Sander W. Tas, Laura Boekel, Gerrit J. Wolbink, Anneke J. van der Kooi, Joost Raaphorst, R. Bart Takkenberg, Geert R.A.M. D’Haens, Phyllis I. Spuls, Marcel W. Bekkenk, Annelie H. Musters, Nicoline F. PostAngela L. Bosma, Marc L. Hilhorst, Yosta Vegting, Frederike J. Bemelman, Alexandre E. Voskuyl, Bo Broens, Agner Parra Sanchez, Cécile A.C.M. van Els, Jelle de Wit, Abraham Rutgers, Karina de Leeuw, Barbara Horváth, Jan J.G.M. Verschuuren, Annabel M. Ruiter, Lotte van Ouwerkerk, Diane van der Woude, Renée C.F. Allaart, Y. K.Onno Teng, Pieter van Paassen, Matthias H. Busch, Papay B.P. Jallah, Esther Brusse, Pieter A. van Doorn, Adája E. Baars, Dirk Jan Hijnen, Corine R.G. Schreurs, W. Ludo van der Pol, H. Stephan Goedee, Maurice Steenhuis, Sofie Keijzer, Jim B.D. Keijser, Olvi Cristianawati, Filip Eftimov*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

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.

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%).

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.

Original languageEnglish
Article number332
Number of pages11
JournalBMC Infectious Diseases
Issue number1
Early online date17 May 2023
Publication statusPublished - Dec 2023

Bibliographical note

Funding Information:
We would like to thank ZonMw (The Netherlands Organization for Health Research and Development, grant 10430072010007) for the funding of the study and the T2B partners, including the patient groups and Health Holland for the support in this study. This collaboration project is financed by the PPP Allowance made available by Top Sector Life Sciences & Health to Samenwerkende Gezondheidsfondsen (SGF) under project number LSHM18055-SGF to stimulate public-private partnerships and co-financing by health foundations that are part of the SGF. Also, we would like to thank E.P. Moll van Charante, J.A Bogaards and R.A. Scholte for their guidance in the data safety monitoring board.

Funding Information:
This study was supported by ZonMw (The Netherlands Organization for Health Research and Development; project number 10430072010007). The sponsor had no role in the design, analysis or reporting of the study.

Publisher Copyright:
© 2023, The Author(s).


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