TY - JOUR
T1 - Clinical and humoral response after SARS-CoV-2 breakthrough infection in patients receiving immunosuppressant therapy
AU - Stalman, Eileen W.
AU - Wieske, Luuk
AU - Keijser, Jim B.D.
AU - van Dam, Koos P.J.
AU - Kummer, Laura Y.L.
AU - Wilbrink, Maarten F.
AU - van Kempen, Zoé L.E.
AU - Killestein, Joep
AU - Volkers, Adriaan G.
AU - Tas, Sander W.
AU - Boekel, Laura
AU - Wolbink, Gerrit J.
AU - van der Kooi, Anneke J.
AU - Raaphorst, Joost
AU - Löwenberg, Mark
AU - Takkenberg, R. Bart
AU - D'Haens, Geert R.A.M.
AU - Spuls, Phyllis I.
AU - Bekkenk, Marcel W.
AU - Musters, Annelie H.
AU - Post, Nicoline F.
AU - Bosma, Angela L.
AU - Hilhorst, Marc L.
AU - Vegting, Yosta
AU - Bemelman, Frederique J.
AU - Voskuyl, Alexandre E.
AU - Broens, Bo
AU - Parra Sanchez, Agner
AU - van Els, Cécile A.C.M.
AU - de Wit, Jelle
AU - Rutgers, Abraham
AU - de Leeuw, Karina
AU - Horváth, Barbara
AU - Verschuuren, Jan J.G.M.
AU - Ruiter, Annabel M.
AU - van Ouwerkerk, Lotte
AU - van der Woude, Diane
AU - Allaart, Renée C.F.
AU - Onno Teng, Y. K.
AU - van Paassen, Pieter
AU - Busch, Matthias H.
AU - Brusse, Esther
AU - van Doorn, Pieter A.
AU - Baars, Adája E.
AU - Hijnen, Dirkjan
AU - Schreurs, Corine R.G.
AU - van der Pol, W. Ludo
AU - Goedee, H. Stephan
AU - Steenhuis, Maurice
AU - Keijzer, Sofie
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/9
Y1 - 2024/9
N2 - 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.
AB - 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.
KW - autoimmune disease
KW - breakthrough infection
KW - humoral response
KW - immunosuppressants
KW - SARS-CoV-2
UR - http://www.scopus.com/inward/record.url?scp=85196480210&partnerID=8YFLogxK
U2 - 10.1016/j.jaci.2024.04.031
DO - 10.1016/j.jaci.2024.04.031
M3 - Article
C2 - 38763170
AN - SCOPUS:85196480210
SN - 0091-6749
VL - 154
SP - 754-766.e7
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 3
ER -