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 - Sanchez, Agner Parra
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 - Teng, Y K Onno
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
AU - T2B! immunity against SARS-CoV-2 study group
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 - Auto-immune disease
KW - Breakthrough infections
KW - Humoral responses
KW - Immunosuppressants
KW - SARS-CoV-2
U2 - 10.1016/j.jaci.2024.04.031
DO - 10.1016/j.jaci.2024.04.031
M3 - Article
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 -