Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Sep;154(3):754-766.e7.
doi: 10.1016/j.jaci.2024.04.031. Epub 2024 May 17.

Clinical and humoral response after SARS-CoV-2 breakthrough infection in patients receiving immunosuppressant therapy

Eileen W Stalman  1 , Luuk Wieske  2 , Jim B D Keijser  3 , Koos P J van Dam  4 , Laura Y L Kummer  5 , Maarten F Wilbrink  4 , Zoé L E van Kempen  6 , Joep Killestein  6 , Adriaan G Volkers  7 , Sander W Tas  8 , Laura Boekel  8 , Gerrit J Wolbink  9 , Anneke J van der Kooi  4 , Joost Raaphorst  4 , Mark Löwenberg  7 , R Bart Takkenberg  7 , Geert R A M D'Haens  7 , Phyllis I Spuls  10 , Marcel W Bekkenk  10 , Annelie H Musters  10 , Nicoline F Post  10 , Angela L Bosma  10 , Marc L Hilhorst  11 , Yosta Vegting  11 , Frederique J Bemelman  11 , Alexandre E Voskuyl  12 , Bo Broens  12 , Agner Parra Sanchez  13 , Cécile A C M van Els  14 , Jelle de Wit  15 , Abraham Rutgers  16 , Karina de Leeuw  16 , Barbara Horváth  17 , Jan J G M Verschuuren  18 , Annabel M Ruiter  18 , Lotte van Ouwerkerk  19 , Diane van der Woude  19 , Renée C F Allaart  19 , Y K Onno Teng  20 , Pieter van Paassen  21 , Matthias H Busch  21 , Esther Brusse  22 , Pieter A van Doorn  22 , Adája E Baars  22 , Dirkjan Hijnen  23 , Corine R G Schreurs  23 , W Ludo van der Pol  24 , H Stephan Goedee  24 , Maurice Steenhuis  3 , Sofie Keijzer  3 , Olvi Cristianawati  3 , Anja Ten Brinke  3 , Niels J M Verstegen  3 , Koos A H Zwinderman  25 , S Marieke van Ham  26 , Theo Rispens  3 , Matthijs R Welkers  27 , Marcel Jonges  27 , Filip Eftimov  4 , Taco W Kuijpers  28 ; T2B! immunity against SARS-CoV-2 study group
Affiliations
Free article

Clinical and humoral response after SARS-CoV-2 breakthrough infection in patients receiving immunosuppressant therapy

Eileen W Stalman et al. J Allergy Clin Immunol. 2024 Sep.
Free article

Abstract

Background: Despite impaired humoral response in patients treated with immunosuppressants (ISPs), recent studies found similar severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection compared to controls. One potential explanation is the rapid generation of humoral response on infection, but evidence is lacking.

Objectives: We investigated the longitudinal dynamics of the SARS-CoV-2 antibody repertoire after SARS-CoV-2 delta and omicron breakthrough infection in patients with immune-mediated inflammatory diseases (IMIDs) receiving ISP therapy and controls.

Methods: As a prospective substudy of the national Target-to-B! (T2B!) consortium, we included IMID patients receiving ISPs therapy and controls who reported SARS-CoV-2 breakthrough infection between July 1, 2021, and April 1, 2022. To get an impression of the dynamics of the antibody repertoire, 3 antibody titers of wild-type RBD, wild-type S, and omicron RBD were measured at 4 time points after SARS-CoV-2 breakthrough infection.

Results: We included 302 IMID patients receiving ISPs and 178 controls. Antibody titers increased up to 28 days after breakthrough infection in both groups. However, in IMID patients receiving therapy with anti-CD20 and sphingosine-1 phosphate receptor modulators, antibody titers were considerably lower compared to controls. In the anti-TNF group, we observed slightly lower antibody titers in the early stages and a faster decline of antibodies after infection compared to controls. Breakthrough infections were mostly mild, and hospitalization was required in less than 1% of cases.

Conclusions: Most ISPs do not influence the dynamics of the SARS-CoV-2 antibody repertoire and exhibit a rapid recall response with cross-reactive antibody clones toward new virus variants. However, in patients treated with anti-CD20 therapy or sphingosine-1 phosphate receptor modulators, the dynamics were greatly impaired, and to a lesser extent in those who received anti-TNF. Nevertheless, only a few severe breakthrough cases were reported.

Keywords: SARS-CoV-2; autoimmune disease; breakthrough infection; humoral response; immunosuppressants.

PubMed Disclaimer

Substances