Longitudinal Dynamics of the SARS-CoV-2 Antibody Repertoire after SARS-CoV-2 Delta and Omicron Breakthrough Infections in Patients with Immune-Mediated Inflammatory Diseases

Abstract

Background: Despite impaired humoral responses after SARS-CoV-2 vaccination, the incidence and severity of SARS-CoV-2 breakthrough infections is not increased in patients with immune-mediated inflammatory diseases (IMID) patients on immunosuppressants (ISPs). This could be explained by preserved humoral recall responses but data are lacking. This study aimed to investigate longitudinal dynamics in humoral response after SARS-CoV-2 delta and omicron breakthrough infections in IMID patients on ISPs compared to controls.

Methods: This is a sub-study of the ongoing national Target-to-B! (T2B!) study, focusing on SARS-CoV-2 vaccination responses in IMID patients. We included IMID patients on ISPs and controls (IMID patients not on ISPs and healthy individuals) who had completed primary vaccinations and reported SARS-CoV-2 breakthrough infections between July 1, 2021, and April 1, 2022, during the prevalence of delta and omicron variants. Antibody titers against wild-type RBD, wild-type S, and omicron RBD were measured at various time points post-infection to assess humoral responses. Dynamics in humoral responses were assessed for IMID patients and controls separately, and compared between IMID patients on different ISPs and controls.

Findings: We included 480 participants. Dynamics in humoral response were comparable between IMID patients on ISPs and controls following SARS-CoV-2 delta or omicron breakthrough infections. However, IMID patients on anti-CD20 therapy and S1P modulators showed greatly impaired humoral responses and those on anti-TNF therapy showed moderately greater decline in antibodies than controls.

Interpretations: Most ISPs do not influence humoral recall responses after SARS-CoV-2 delta and omicron breakthrough infections, with the exception of anti-CD20 and S1P modulators, and to a lesser extent by anti-TNF, which shows a more rapid antibody decay.

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

Declaration of Interest: F Eftimov and T Kuijpers report (governmental) grants from ZonMw to study immune response after SARS-Cov2 vaccination in auto-immune diseases. F Eftimov also reports grants from Prinses Beatrix Spierfonds, CSL Behring, Kedrion, Terumo BCT, Grifols, Takeda Pharmaceutical Company, and GBS-CIDP Foundation; consulting fees from UCB Pharma and CSL Behring; honoraria from Grifols. AJ van der Kooi reports grants from CSL Behring and participation on an advisory board for Argen-X. M Löwenberg reports a grant from Galapagos not related to this study, and honoraria from Bristol Myers Squibb, Pfizer, Takeda, and Tillotts. Ph I Spuls is involved in performing clinical trials with many pharmaceutical industries that manufacture drugs used for the treatment of e.g. psoriasis and atopic dermatitis, for which financial compensation is paid to the department/hospital and is a chief investigator of the TREAT NL registry taskforce and SECURE-AD registry. M.W. Bekkenk is a secretary for Dutch Experimental Dermatology Board and head of the pigmentary disorders group within the Dutch Dermatology Board, and reports honoraria from Pfizer, Sanofi, Novartis and Fondation René Touraine. J Killestein has speaking relationships with Merck Serono, Biogen Idec, TEVA, Sanofi, Genzyme, Roche and Novartis; Amsterdam UMC, location VUmc, MS Center Amsterdam has received financial support for research activities from Merck Serono, Bayer Shcering Pharma, Biogen Idec, GlaxoSmithKline, Roche, Teva, Sanofi, Genzyme, GlaxoSmithKline, and Novartis. B Horváth reports unpaid positions as medical advisor for several patient groups, a board position for ERN-SKIN, and associate editor for The British Journal of Dermatology; reports grants from Abbvie, Akari Therapeutics, Celgene, and Novartis; consulting fees from UCB Pharma, Novartis and Janssen-Cilag; honoraria from Abbvie. J.J.G.M. Verschuuren reports consulting fees from Argenx, Alexion and NMD Pharma; is coinventor on patent applications based on MuSK-related research. DJ Hijnen reports grants from Abbvie, AstraZeneca, Janssen, LEO Pharma and UCB Pharma, and honoraria from Abbvie, Galderma, Janssen, Lilly, Pfizer, Sanofi and UCB Pharma, and a paid position in an advisory board for BIOMAP IMI. P.A. van Doorn participated on an advisory board for Octapharma. P. van Paassen reports grants from Alexion Pharma and GSK; and participation on GSK and Vifor Pharma advisory boards. G.R.A.M. D'Haens reports consulting fees from Abbvie, Agomab, AstraZeneca, AM Pharma, AMT, Arena Pharmaceuticals, Bristol Meiers Squibb, Boehringer Ingelheim, Celltrion, Eli Lilly, Exeliom Biosciences, Exo Biologics, Galapagos, Index Pharmaceuticals, Kaleido, Roche, Gilead, Glaxo Smith Kline, Gossamerbio, Pfizer, Immunic, Johnson and Johnson, Origo, Polpharma, Procise Diagnostics, Prometheus laboratories, Prometheus Biosciences, Progenity, and Protagonist; honoraria from Abbvie, Arena, Galapagos, Gilead, Pfizer, BMS, Takeda; participation on advisory boards for Abbvie, Seres Health, Galapagos, and AstraZeneca. R.B. Takkenberg reports honoraria from Sobi and Norgine and participation in an advisory board for Norgine. SH Goedee is a board member of the Dutch Society of Clinical Neurophysiology (unpaid), reports grants from Prinses Beatrix Spierfonds, and received speaker fees from Shire/Takeda. AH Zwinderman reports paid data safety monitoring board positions for Torrent Ltd and Foresee Pharmaceuticals Co. No other disclosures were reported.

Ethical Approval: The medical ethical committee of the Amsterdam UMC, location AMC (2020.194) approved the study.

Keywords: SARS-CoV-2 breaktrough infections, immune-mediated inflammaatory diseases, immunosuppressants, humoral responses