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Disease Activity after Sars-Cov-2 Delta and Omicron Breakthrough Infections in Patients with Immune-Mediated Inflammatory Diseases

15 Pages Posted: 15 Jul 2024 Publication Status: Under Review

See all articles by Eileen Stalman

Eileen Stalman

Amsterdam UMC - Department of Neurology and Neurophysiology

P.J. van Dam

Amsterdam UMC - Department of Neurology and Neurophysiology

Laura Kummer

Amsterdam UMC - Department of Neurology and Neurophysiology

Zoé van Kempen

Amsterdam UMC, Vrije Universiteit - Department of Neurology

Joep Killestein

Amsterdam UMC, Vrije Universiteit - Department of Neurology

Adriaan G. Volkers

University of Amsterdam - Department of Gastroenterology and Hepatology

Sander Tas

University of Amsterdam - Department of Rheumatology and Clinical Immunology

Anneke J. van der Kooi

University of Amsterdam - Department of Neurology

Joost Raaphorst

University of Amsterdam - Department of Neurology

Laura Boekel

University of Amsterdam - Amsterdam Rheumatology and Immunology Centre, Location Reade

Gertjan Wolbink

University of Amsterdam - Amsterdam Rheumatology and Immunology Centre

Mark Löwenberg

affiliation not provided to SSRN

R. Bart Takkenberg

University of Amsterdam - Department of Gastroenterology and Hepatology

Geert R.A.M. D'Haens

University of Amsterdam - University Medical Center; VU University Amsterdam - Department of Epidemiology & Data Science

Phyllis I. Spuls

University of Amsterdam - Department of Dermatology

Marcel W. Bekkenk

University of Amsterdam - Department of Dermatology

Annelie H. Musters

University of Amsterdam - Department of Dermatology

Nicoline F. Post

University of Amsterdam - Department of Dermatology

Angela L. Bosma

University of Amsterdam - Department of Dermatology

Marc L. Hilhorst

University of Amsterdam - Department of Internal Medicine

Yosta Vegting

University of Amsterdam - Department of Internal Medicine

Frederike J. Bemelman

University of Amsterdam - Department of Internal Medicine

Alexandre Voskuyl

VU University Medical Center - Amsterdam Rheumatology and Immunology Center

Bo Broens

University of Amsterdam - Department of Clinical Immunology and Rheumatology

Agner Parra Sanchez

University of Amsterdam - Department of Clinical Immunology and Rheumatology

Cecile van Els

National Institute for Public Health and the Environment (RIVM) - Centre for Infectious Disease Control

Jelle de Wit

National Institute for Public Health and the Environment (RIVM) - Centre for Infectious Disease Control

Abraham Rutgers

University of Groningen - University Medical Center Groningen (UMCG)

Karina de Leeuw

University of Groningen - Department of Rheumatology and Clinical Immunology

Barbara Horváth

University of Groningen - Department of Dermatology

Jan J.G.M. Verschuuren

Leiden University - Department of Neurology

Annabel M. Ruiter

Leiden University - Department of Neurology

Lotte van Ouwerkerk

Leiden University - Department of Rheumatology

Diane van der Woude

Leiden University - Department of Rheumatology

Cornelia F. Allaart

Leiden University - Department of Rheumatology

Onno YK Teng

Leiden University - Department of Nephrology

Pieter van Paassen

Maastricht University - Division of Nephrology and Clinical Immunology

Matthias Busch

Department of Immunology, Maastricht UMC+

Esther Brusse

Erasmus University Rotterdam (EUR) - Department of Neurology

Pieter van Doorn

Erasmus University Rotterdam (EUR) - Department of Neurology

Adája E. Baars

Erasmus University Rotterdam (EUR) - Department of Neurology

Dirk Jan Hijnen

Erasmus University Rotterdam (EUR) - Department of Dermatology

Corine R.G. Schreurs

Erasmus University Rotterdam (EUR) - Department of Dermatology

Ludo van der Pol

Utrecht University - Brain Center Rudolf Magnus

H. Stephan Goedee

Utrecht University - University Medical Center (Utrecht)

Maurice Steenhuis

Sanquin Research - Department of Immunopathology

Jim Keijser

Sanquin Research - Department of Immunopathology

Sofie Keijzer

Sanquin Research - Department of Immunopathology

Olvi Cristianawati

Sanquin Research - Department of Immunopathology

Anja ten Brinke

Sanquin Research

Niels Verstegen

Sanquin Research

Aeilko H. Zwinderman

University of Amsterdam - University Medical Center

Marieke van Ham

Sanquin Research - Department of Immunopathology

Theo Rispens

Sanquin Research - Department of Immunopathology

Taco Kuijpers

University of Amsterdam - Department of Pediatric Immunology, Rheumatology and Infectious Disease

Filip Eftimov

Amsterdam UMC - Department of Neurology and Neurophysiology

Luuk Wieske

Amsterdam UMC - Department of Neurology and Neurophysiology

T2B! Immunity Against SARS-CoV-2 Study Group

Independent

Abstract

Abstract   Objective It has been suggested that SARS-CoV-2 infections prior to primary vaccination are associated with increased disease activity of underlying immune-mediated inflammatory diseases (IMIDs). Our primary objective was to assess the incidence of increased disease activity after SARS-CoV-2 breakthrough infections in patients with IMIDs, and study risk factors associated with increased disease activity.   Methods IMID patients, enrolled in the prospective Target-to-B! (T2B!) study, who completed primary vaccination and reported a positive SARS-CoV-2 test between 1 July 2021 and 1 April 2022 were included. Patients reported increased disease activity (yes/no) in surveys at 7 and 28 days after a positive test. Also, proportions of patients who consulted their treating physician, confirmation of increased disease activity by the treating physician, and intensification of immunosuppressive (ISP) treatment were analyzed. Multivariate models were used to identify determinants associated with increased disease activity.   Results We included 457 IMID patients who reported a breakthrough infection. Increased disease activity at 7 and/or 28 days was reported by 148/457 (32.4%; 95% CI 28.3-36.8) patients. Of these, 35/148 (23.6%) consulted their treating physician. Treating physicians confirmed increased disease activity in 20/148 (13.5%) and intensified ISP treatment in 11/148 (7.4%). Factors associated with increased disease activity were ‘recent increase in disease activity prior to the breakthrough infection’, ‘increased disease activity after SARS-CoV-2 vaccination’, and ‘neurological IMIDs’.   Conclusions Approximately one third of the IMID patients reported increased disease activity after SARS-CoV-2 breakthrough infection, but treatment was rarely intensified. These results are reassuring for IMID patients and their treating physicians.

Note:
Funding Information: 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 Interests: None.

Ethics Approval Statement: This is a substudy of a prospective multicenter cohort study, the Target-to-B! (T2B!) study (Trial ID: NL8900; Dutch Trial Register) which was approved by the medical ethical committee of the Amsterdam UMC (2020.194). Signed informed consent was obtained from all participants.

Keywords: autoimmune disease, COVID-19, Disease Activity, SARS-CoV-2 breakthrough infections

Suggested Citation

Stalman, Eileen and van Dam, Koos and Kummer, Laura and van Kempen, Zoé and Killestein, Joep and Volkers, Adriaan G. and Tas, Sander and van der Kooi, Anneke J. and Raaphorst, Joost and Boekel, Laura and Wolbink, Gertjan and Löwenberg, Mark and Takkenberg, R. Bart and D'Haens, Geert R.A.M. and Spuls, Phyllis I. and Bekkenk, Marcel W. and Musters, Annelie H. and Post, Nicoline F. and Bosma, Angela L. and Hilhorst, Marc L. and Vegting, Yosta and Bemelman, Frederike J. and Voskuyl, Alexandre and Broens, Bo and Sanchez, Agner Parra and van Els, Cecile and de Wit, Jelle and Rutgers, Abraham and de Leeuw, Karina and Horváth, Barbara and Verschuuren, Jan J.G.M. and Ruiter, Annabel M. and van Ouwerkerk, Lotte and van der Woude, Diane and Allaart, Cornelia F. and Teng, Onno YK and van Paassen, Pieter and Busch, Matthias and Brusse, Esther and van Doorn, Pieter and Baars, Adája E. and Hijnen, Dirk Jan and Schreurs, Corine R.G. and van der Pol, Ludo and Goedee, H. Stephan and Steenhuis, Maurice and Keijser, Jim and Keijzer, Sofie and Cristianawati, Olvi and ten Brinke, Anja and Verstegen, Niels and Zwinderman, Aeilko H. and van Ham, Marieke and Rispens, Theo and Kuijpers, Taco and Eftimov, Filip and Wieske, Luuk and Study Group, T2B! Immunity Against SARS-CoV-2, Disease Activity after Sars-Cov-2 Delta and Omicron Breakthrough Infections in Patients with Immune-Mediated Inflammatory Diseases. Available at SSRN: https://ssrn.com/abstract=4885476 or http://dx.doi.org/10.2139/ssrn.4885476

Eileen Stalman (Contact Author)

Amsterdam UMC - Department of Neurology and Neurophysiology ( email )

Netherlands

Koos Van Dam

Amsterdam UMC - Department of Neurology and Neurophysiology ( email )

Meibergdreef 9
Amsterdam, Noord Holland 1105
Netherlands

Laura Kummer

Amsterdam UMC - Department of Neurology and Neurophysiology ( email )

Netherlands

Zoé Van Kempen

Amsterdam UMC, Vrije Universiteit - Department of Neurology ( email )

Spui 21
Amsterdam, 1018 WB
Netherlands

Joep Killestein

Amsterdam UMC, Vrije Universiteit - Department of Neurology ( email )

Meibergdreef 9
Amsterdam, Noord Holland 1105
Netherlands

Adriaan G. Volkers

University of Amsterdam - Department of Gastroenterology and Hepatology ( email )

Sander Tas

University of Amsterdam - Department of Rheumatology and Clinical Immunology ( email )

Amsterdam
Netherlands

Anneke J. Van der Kooi

University of Amsterdam - Department of Neurology ( email )

Joost Raaphorst

University of Amsterdam - Department of Neurology ( email )

Laura Boekel

University of Amsterdam - Amsterdam Rheumatology and Immunology Centre, Location Reade ( email )

Amsterdam
Netherlands

Gertjan Wolbink

University of Amsterdam - Amsterdam Rheumatology and Immunology Centre ( email )

Amsterdam
Netherlands

Mark Löwenberg

affiliation not provided to SSRN ( email )

No Address Available

R. Bart Takkenberg

University of Amsterdam - Department of Gastroenterology and Hepatology ( email )

Geert R.A.M. D'Haens

University of Amsterdam - University Medical Center ( email )

VU University Amsterdam - Department of Epidemiology & Data Science ( email )

Phyllis I. Spuls

University of Amsterdam - Department of Dermatology ( email )

Marcel W. Bekkenk

University of Amsterdam - Department of Dermatology ( email )

Annelie H. Musters

University of Amsterdam - Department of Dermatology ( email )

Nicoline F. Post

University of Amsterdam - Department of Dermatology ( email )

Angela L. Bosma

University of Amsterdam - Department of Dermatology ( email )

Marc L. Hilhorst

University of Amsterdam - Department of Internal Medicine ( email )

Yosta Vegting

University of Amsterdam - Department of Internal Medicine ( email )

Frederike J. Bemelman

University of Amsterdam - Department of Internal Medicine ( email )

Alexandre Voskuyl

VU University Medical Center - Amsterdam Rheumatology and Immunology Center ( email )

Bo Broens

University of Amsterdam - Department of Clinical Immunology and Rheumatology ( email )

Agner Parra Sanchez

University of Amsterdam - Department of Clinical Immunology and Rheumatology ( email )

Cecile Van Els

National Institute for Public Health and the Environment (RIVM) - Centre for Infectious Disease Control

Jelle De Wit

National Institute for Public Health and the Environment (RIVM) - Centre for Infectious Disease Control ( email )

Abraham Rutgers

University of Groningen - University Medical Center Groningen (UMCG) ( email )

Hanzeplein 1
Groningen, 9713
Netherlands

Karina De Leeuw

University of Groningen - Department of Rheumatology and Clinical Immunology ( email )

Groningen
Netherlands

Barbara Horváth

University of Groningen - Department of Dermatology ( email )

Jan J.G.M. Verschuuren

Leiden University - Department of Neurology ( email )

Annabel M. Ruiter

Leiden University - Department of Neurology ( email )

Lotte Van Ouwerkerk

Leiden University - Department of Rheumatology ( email )

Leiden, 2333 ZA
Netherlands

Diane Van der Woude

Leiden University - Department of Rheumatology ( email )

Cornelia F. Allaart

Leiden University - Department of Rheumatology ( email )

Leiden, 2333 ZA
Netherlands

Onno YK Teng

Leiden University - Department of Nephrology ( email )

Pieter Van Paassen

Maastricht University - Division of Nephrology and Clinical Immunology ( email )

Netherlands

Matthias Busch

Department of Immunology, Maastricht UMC+ ( email )

Esther Brusse

Erasmus University Rotterdam (EUR) - Department of Neurology ( email )

Pieter Van Doorn

Erasmus University Rotterdam (EUR) - Department of Neurology

Adája E. Baars

Erasmus University Rotterdam (EUR) - Department of Neurology ( email )

Dirk Jan Hijnen

Erasmus University Rotterdam (EUR) - Department of Dermatology ( email )

Corine R.G. Schreurs

Erasmus University Rotterdam (EUR) - Department of Dermatology ( email )

Ludo Van der Pol

Utrecht University - Brain Center Rudolf Magnus ( email )

Utrecht
Netherlands

H. Stephan Goedee

Utrecht University - University Medical Center (Utrecht) ( email )

Maurice Steenhuis

Sanquin Research - Department of Immunopathology

Amsterdam
Netherlands

Jim Keijser

Sanquin Research - Department of Immunopathology ( email )

Netherlands

Sofie Keijzer

Sanquin Research - Department of Immunopathology

Amsterdam
Netherlands

Olvi Cristianawati

Sanquin Research - Department of Immunopathology ( email )

Netherlands

Anja Ten Brinke

Sanquin Research ( email )

Amsterdam
Netherlands

Niels Verstegen

Sanquin Research ( email )

Aeilko H. Zwinderman

University of Amsterdam - University Medical Center ( email )

Marieke Van Ham

Sanquin Research - Department of Immunopathology

Amsterdam
Netherlands

Theo Rispens

Sanquin Research - Department of Immunopathology

Amsterdam
Netherlands

Taco Kuijpers

University of Amsterdam - Department of Pediatric Immunology, Rheumatology and Infectious Disease ( email )

Filip Eftimov

Amsterdam UMC - Department of Neurology and Neurophysiology ( email )

Spui 21
Amsterdam, 1018 WB
Netherlands

Luuk Wieske

Amsterdam UMC - Department of Neurology and Neurophysiology ( email )

Spui 21
Amsterdam, 1018 WB
Netherlands

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