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

Author:

Dam Koos van1ORCID,Volkers Adriaan1,Wieske Luuk1,Stalman Eileen1,Kummer Laura2,kempen Zoe van3,Killestein Joep4,Tas Sander1,Boekel Laura5,Wolbink Gertjan5,Kooi Anneke van der1,Raaphorst Joost1,Takkenberg Bart1,D'Haens Geert1,Spuls Phyllis1,Bekkenk Marcel1,Musters Annelie1,Post Nicoline1,Bosma Angela1,Hilhorst Marc1,Vegting Yosta1,Bemelman Frederike1,Voskuyl Alexandre3,Broens Bo4,Sanchez Agner Parra4,Els Cecile van6,de Wit Jelle6,Rutgers Abraham7,de Leeuw Karina7,Horvath Barbara7,Verschuuren Jan8,Ruiter Annabel8,Ouwerkerk Lotte van8,Woude Diane van der8,Allaart Renee8,Teng Onno8,Paassen Pieter van9,Busch Matthias9,Jallah Papay9,Brusse Esther10,Doorn Pieter van10,Baars Adaja10,Hijnen DirkJan10,Schreurs Corine10,Pol Ludo van der11,Goedee Stephan11,Steenhuis Maurice2,Keijzer Sofie2,Keijser Jim2,Cristianawati Olvi2,Brinke Anja ten2,Verstegen Niels2,Ham Marieke van2,Rispens Theo2,Kuijpers Taco1,Lowenberg Mark1,Eftimov Filip1

Affiliation:

1. Amsterdam UMC - Locatie AMC: Amsterdam UMC Locatie AMC

2. Sanquin Research

3. Amsterdam UMC - VUMC location: Amsterdam UMC Locatie VUmc

4. Amsterdam UMC - Locatie VUMC: Amsterdam UMC Locatie VUmc

5. Amsterdam Rheumatology and Immunology Center

6. RIVM: Rijksinstituut voor Volksgezondheid en Milieu

7. UMCG: Universitair Medisch Centrum Groningen

8. LUMC: Leids Universitair Medisch Centrum

9. Maastricht UMC+: Maastricht Universitair Medisch Centrum+

10. Erasmus MC

11. UMC Utrecht: Universitair Medisch Centrum Utrecht

Abstract

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.

Publisher

Research Square Platform LLC

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