T cell responses to repeated SARS-CoV-2 vaccination and breakthrough infections in patients on TNF inhibitor treatment: a prospective cohort studyResearch in context
Asia-Sophia Wolf,
Kristin H. Bjørlykke,
Hilde S. Ørbo,
Sabin Bhandari,
Guri Solum,
Ingrid Fadum Kjønstad,
Ingrid Jyssum,
Unni C. Nygaard,
Anja Bråthen Kristoffersen,
Ingrid E. Christensen,
Sarah E. Josefsson,
Katrine Persgård Lund,
Adity Chopra,
Julie Røkke Osen,
Viktoriia Chaban,
Anne T. Tveter,
Joseph Sexton,
Tore K. Kvien,
Jørgen Jahnsen,
Espen A. Haavardsholm,
Gunnveig Grødeland,
John Torgils Vaage,
Sella A. Provan,
Hassen Kared,
Fridtjof Lund-Johansen,
Ludvig A. Munthe,
Silje Watterdal Syversen,
Guro Løvik Goll,
Kristin Kaasen Jørgensen,
Siri Mjaaland
Affiliations
Asia-Sophia Wolf
Division of Infection Control, Section for Immunology, Norwegian Institute of Public Health, Oslo, Norway; Corresponding author. Section for Immunology, Norwegian Institute of Public Health, Lovisenberggata 8, 0456, Oslo, Norway.
Kristin H. Bjørlykke
Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway
Hilde S. Ørbo
Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Center for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway
Sabin Bhandari
Division of Infection Control, Section for Immunology, Norwegian Institute of Public Health, Oslo, Norway
Guri Solum
Division of Infection Control, Section for Immunology, Norwegian Institute of Public Health, Oslo, Norway
Ingrid Fadum Kjønstad
Division of Infection Control, Section for Immunology, Norwegian Institute of Public Health, Oslo, Norway
Ingrid Jyssum
Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Center for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway
Unni C. Nygaard
Division of Infection Control, Section for Immunology, Norwegian Institute of Public Health, Oslo, Norway
Anja Bråthen Kristoffersen
Division of Infection Control, Section for Modelling and Bioinformatics, Norwegian Institute of Public Health, Oslo, Norway
Ingrid E. Christensen
Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Center for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway
Sarah E. Josefsson
Division of Infection Control, Section for Immunology, Norwegian Institute of Public Health, Oslo, Norway
Katrine Persgård Lund
Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Immunology, Oslo University Hospital, Oslo, Norway; KG Jebsen Centre for B Cell Malignancy, University of Oslo, Oslo, Norway
Adity Chopra
Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Immunology, Oslo University Hospital, Oslo, Norway
Julie Røkke Osen
Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Immunology, Oslo University Hospital, Oslo, Norway; KG Jebsen Centre for B Cell Malignancy, University of Oslo, Oslo, Norway
Viktoriia Chaban
Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Immunology, Oslo University Hospital, Oslo, Norway; KG Jebsen Centre for B Cell Malignancy, University of Oslo, Oslo, Norway
Anne T. Tveter
Center for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway; Faculty of Health Sciences, Oslo Metropolitan University, Oslo, Norway
Joseph Sexton
Center for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway
Tore K. Kvien
Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Center for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway
Jørgen Jahnsen
Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway
Espen A. Haavardsholm
Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Center for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway
Gunnveig Grødeland
Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Immunology, Oslo University Hospital, Oslo, Norway
John Torgils Vaage
Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Immunology, Oslo University Hospital, Oslo, Norway
Sella A. Provan
Center for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway; Section for Public Health, Inland Norway University of Applied Sciences, Norway
Hassen Kared
Department of Immunology, Oslo University Hospital, Oslo, Norway; KG Jebsen Centre for B Cell Malignancy, University of Oslo, Oslo, Norway
Fridtjof Lund-Johansen
Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Immunology, Oslo University Hospital, Oslo, Norway
Ludvig A. Munthe
Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Immunology, Oslo University Hospital, Oslo, Norway; KG Jebsen Centre for B Cell Malignancy, University of Oslo, Oslo, Norway
Silje Watterdal Syversen
Center for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway; Institute of Health and Society, University of Oslo, Norway
Guro Løvik Goll
Center for Treatment of Rheumatic and Musculoskeletal Diseases (REMEDY), Diakonhjemmet Hospital, Oslo, Norway; Institute of Health and Society, University of Oslo, Norway
Kristin Kaasen Jørgensen
Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway; Corresponding author. Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway.
Siri Mjaaland
Division of Infection Control, Section for Immunology, Norwegian Institute of Public Health, Oslo, Norway
Summary: Background: Understanding cellular responses to SARS-CoV-2 immunisations is important for informing vaccine recommendations in patients with inflammatory bowel disease (IBD) and other vulnerable patients on immunosuppressive therapies. This study investigated the magnitude and quality of T cell responses after multiple SARS-CoV-2 vaccine doses and COVID-19 breakthrough infection. Methods: This prospective, observational study included patients with IBD and arthritis on tumour necrosis factor inhibitors (TNFi) receiving up to four SARS-CoV-2 vaccine doses. T cell responses to SARS-CoV-2 peptides were measured by flow cytometry before and 2–4 weeks after vaccinations and breakthrough infection to assess the frequency and polyfunctionality of responding cells, along with receptor-binding domain (anti-RBD) antibodies. Findings: Between March 2, 2021, and December 20, 2022, 143 patients (118 IBD, 25 arthritis) and 73 healthy controls were included. In patients with either IBD or arthritis, humoral immunity was attenuated compared to healthy controls (median anti-RBD levels 3391 vs. 6280 BAU/ml, p = 0.008) after three SARS-CoV-2 vaccine doses. Patients with IBD had comparable quantities (median CD4 0.11% vs. 0.11%, p = 0.26, CD8 0.031% vs. 0.047%, p = 0.33) and quality (polyfunctionality score: 0.403 vs. 0.371, p = 0.39; 0.105 vs. 0.101, p = 0.87) of spike-specific T cells to healthy controls. Patients with arthritis had lower frequencies but comparable quality of responding T cells to controls. Breakthrough infection increased spike-specific CD8 T cell quality and T cell responses against non-spike peptides. Interpretation: Patients with IBD on TNFi have T cell responses comparable to healthy controls despite attenuated humoral responses following three vaccine doses. Repeated vaccination and breakthrough infection increased the quality of T cell responses. Our study adds evidence that, in the absence of other risk factors, this group may in future be able to follow the general recommendations for COVID-19 vaccines. Funding: South-Eastern Norway Regional Health Authority, Coalition for Epidemic Preparedness Innovations (CEPI), Norwegian Institute of Public Health, Akershus University Hospital, Diakonhjemmet Hospital.
