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

Author

Stalman, Eileen W., Wieske, Luuk, Keijser, Jim B.D., van Dam, Koos P.J., Kummer, Laura Y.L., Wilbrink, Maarten F., van Kempen, Zoé L.E., Killestein, Joep, Volkers, Adriaan G., Tas, Sander W., Boekel, Laura, Wolbink, Gerrit J., van der Kooi, Anneke J., Raaphorst, Joost, Löwenberg, Mark, Takkenberg, R. Bart, D’Haens, Geert R.A.M., Spuls, Phyllis I., Bekkenk, Marcel W., Musters, Annelie H., Post, Nicoline F., Bosma, Angela L., Hilhorst, Marc L., Vegting, Yosta, Bemelman, Frederique J., Voskuyl, Alexandre E., Broens, Bo, Parra Sanchez, Agner, van Els, Cécile A.C. M., de Wit, Jelle, Rutgers, Abraham, de Leeuw, Karina, Horváth, Barbara, Verschuuren, Jan J.G.M., Ruiter, Annabel M., van Ouwerkerk, Lotte, van der Woude, Diane, Allaart, Renée C.F., Onno Teng, Y.K., van Paassen, Pieter, Busch, Matthias H., Brusse, Esther, van Doorn, Pieter A., Baars, Adája E., Hijnen, Dirkjan, Schreurs, Corine R.G., van der Pol, W. Ludo, Goedee, H. Stephan, Steenhuis, Maurice, Keijzer, Sofie, Cristianawati, Olvi, Brinke, Anja ten, Verstegen, Niels J.M., Zwinderman, Koos A.H., van Ham, S. Marieke, Rispens, Theo, Welkers, Matthijs R., Jonges, Marcel, Eftimov, Filip, and Kuijpers, Taco W.

Published
2024
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2. Disease activity in patients with immune-mediated inflammatory diseases after SARS-CoV-2 vaccinations

Author

van Dam, Koos P.J., Wieske, Luuk, Stalman, Eileen W., Kummer, Laura Y.L., Roosen, Jesse, van Kempen, Zoé L.E., Killestein, Joep, Volkers, Adriaan G., Boekel, Laura, Wolbink, Gerrit J., van der Kooi, Anneke J., Raaphorst, Joost, Löwenberg, Mark, Takkenberg, R. Bart, D'Haens, Geert R.A.M., Spuls, Phyllis I., Bekkenk, Marcel W., Musters, Annelie H., Post, Nicoline F., Bosma, Angela L., Hilhorst, Marc L., Vegting, Yosta, Bemelman, Frederike J., Voskuyl, Alexandre E., Broens, Bo, Sanchez, Agner Parra, van Els, Cécile A.C.M., de Wit, Jelle, Rutgers, Abraham, de Leeuw, Karina, Horváth, Barbara, Verschuuren, Jan J.G.M., Ruiter, Annabel M., van Ouwerkerk, Lotte, van der Woude, Diane, Allaart, Renée C.F., Teng, Y.K. Onno, van Paassen, Pieter, Busch, Matthias H., Jallah, Papay B.P., Brusse, Esther, van Doorn, Pieter A., Baars, Adája E., Hijnen, Dirk Jan, Schreurs, Corine R.G., van der Pol, W.Ludo, Goedee, H. Stephan, Steenhuis, Maurice, Keijzer, Sofie, Keijser, Jim B.D., Cristianawati, Olvi, Rispens, Theo, Brinke, Anja ten, Verstegen, Niels J.M., Marieke van Ham, S., Tas, Sander W., Kuijpers, Taco W., and Eftimov, Filip

Published
2023
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3. Clinical and humoral response after SARS-CoV-2 breakthrough infection in patients receiving immunosuppressant therapy

Author

T2B! immunity against SARS-CoV-2 study group, Stalman, Eileen W., Wieske, Luuk, Keijser, Jim B.D., van Dam, Koos P.J., Kummer, Laura Y.L., Wilbrink, Maarten F., van Kempen, Zoé L.E., Killestein, Joep, Volkers, Adriaan G., Tas, Sander W., Boekel, Laura, Wolbink, Gerrit J., van der Kooi, Anneke J., Raaphorst, Joost, Löwenberg, Mark, Takkenberg, R. Bart, D'Haens, Geert R.A.M., Spuls, Phyllis I., Bekkenk, Marcel W., Musters, Annelie H., Post, Nicoline F., Bosma, Angela L., Hilhorst, Marc L., Vegting, Yosta, Bemelman, Frederique J., Voskuyl, Alexandre E., Broens, Bo, Parra Sanchez, Agner, van Els, Cécile A.C.M., de Wit, Jelle, Rutgers, Abraham, de Leeuw, Karina, Horváth, Barbara, Verschuuren, Jan J.G.M., Ruiter, Annabel M., van Ouwerkerk, Lotte, van der Woude, Diane, Allaart, Renée C.F., Onno Teng, Y. K., van Paassen, Pieter, Busch, Matthias H., Brusse, Esther, van Doorn, Pieter A., Baars, Adája E., Hijnen, Dirkjan, Schreurs, Corine R.G., van der Pol, W. Ludo, Goedee, H. Stephan, Steenhuis, Maurice, Keijzer, Sofie, T2B! immunity against SARS-CoV-2 study group, Stalman, Eileen W., Wieske, Luuk, Keijser, Jim B.D., van Dam, Koos P.J., Kummer, Laura Y.L., Wilbrink, Maarten F., van Kempen, Zoé L.E., Killestein, Joep, Volkers, Adriaan G., Tas, Sander W., Boekel, Laura, Wolbink, Gerrit J., van der Kooi, Anneke J., Raaphorst, Joost, Löwenberg, Mark, Takkenberg, R. Bart, D'Haens, Geert R.A.M., Spuls, Phyllis I., Bekkenk, Marcel W., Musters, Annelie H., Post, Nicoline F., Bosma, Angela L., Hilhorst, Marc L., Vegting, Yosta, Bemelman, Frederique J., Voskuyl, Alexandre E., Broens, Bo, Parra Sanchez, Agner, van Els, Cécile A.C.M., de Wit, Jelle, Rutgers, Abraham, de Leeuw, Karina, Horváth, Barbara, Verschuuren, Jan J.G.M., Ruiter, Annabel M., van Ouwerkerk, Lotte, van der Woude, Diane, Allaart, Renée C.F., Onno Teng, Y. K., van Paassen, Pieter, Busch, Matthias H., Brusse, Esther, van Doorn, Pieter A., Baars, Adája E., Hijnen, Dirkjan, Schreurs, Corine R.G., van der Pol, W. Ludo, Goedee, H. Stephan, Steenhuis, Maurice, and Keijzer, Sofie

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 a

Published
2024

4. Primary SARS-CoV-2 infection in patients with immune-mediated inflammatory diseases: long-term humoral immune responses and effects on disease activity

Author

van Dam, Koos P.J., Volkers, Adriaan G., Wieske, Luuk, Stalman, Eileen W., Kummer, Laura Y.L., van Kempen, Zoé L.E., Killestein, Joep, Tas, Sander W., Boekel, Laura, Wolbink, Gerrit J., van der Kooi, Anneke J., Raaphorst, Joost, Takkenberg, R. Bart, D’Haens, Geert R.A.M., Spuls, Phyllis I., Bekkenk, Marcel W., Musters, Annelie H., Post, Nicoline F., Bosma, Angela L., Hilhorst, Marc L., Vegting, Yosta, Bemelman, Frederike J., Voskuyl, Alexandre E., Broens, Bo, Sanchez, Agner Parra, van Els, Cécile A.C.M., de Wit, Jelle, Rutgers, Abraham, de Leeuw, Karina, Horváth, Barbara, Verschuuren, Jan J.G.M., Ruiter, Annabel M., van Ouwerkerk, Lotte, van der Woude, Diane, Allaart, Renée C.F., Teng, Y. K.Onno, van Paassen, Pieter, Busch, Matthias H., Jallah, Papay B.P., Brusse, Esther, van Doorn, Pieter A., Baars, Adája E., Hijnen, Dirk Jan, Schreurs, Corine R.G., van der Pol, W. Ludo, Goedee, H. Stephan, Steenhuis, Maurice, Keijzer, Sofie, Keijser, Jim B.D., Cristianawati, Olvi, Eftimov, Filip, Neurology, and Dermatology

Subjects
SDG 3 - Good Health and Well-being
Abstract

Background: Patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressants (ISPs) may have impaired long-term humoral immune responses and increased disease activity after SARS-CoV-2 infection. We aimed to investigate long-term humoral immune responses against SARS-CoV-2 and increased disease activity after a primary SARS-CoV-2 infection in unvaccinated IMID patients on ISPs. Methods: IMID patients on active treatment with ISPs and controls (i.e. IMID patients not on ISP and healthy controls) with a confirmed SARS-CoV-2 infection before first vaccination were included from an ongoing prospective cohort study (T2B! study). Clinical data on infections and increased disease activity were registered using electronic surveys and health records. A serum sample was collected before first vaccination to measure SARS-CoV-2 anti-receptor-binding domain (RBD) antibodies. Results: In total, 193 IMID patients on ISP and 113 controls were included. Serum samples from 185 participants were available, with a median time of 173 days between infection and sample collection. The rate of seropositive IMID patients on ISPs was 78% compared to 100% in controls (p < 0.001). Seropositivity rates were lowest in patients on anti-CD20 (40.0%) and anti-tumor necrosis factor (TNF) agents (60.5%), as compared to other ISPs (p < 0.001 and p < 0.001, respectively). Increased disease activity after infection was reported by 68 of 260 patients (26.2%; 95% CI 21.2–31.8%), leading to ISP intensification in 6 out of these 68 patients (8.8%). Conclusion: IMID patients using ISPs showed reduced long-term humoral immune responses after primary SARS-CoV-2 infection, which was mainly attributed to treatment with anti-CD20 and anti-TNF agents. Increased disease activity after SARS-CoV-2 infection was reported commonly, but was mostly mild. Trial registration: NL74974.018.20, Trial ID: NL8900. Registered on 9 September 2020.

Published
2023

5. Disease activity in patients with immune-mediated inflammatory diseases after SARS-CoV-2 vaccinations

Author

Neurologen, Brain, van Dam, Koos P.J., Wieske, Luuk, Stalman, Eileen W., Kummer, Laura Y.L., Roosen, Jesse, van Kempen, Zoé L.E., Killestein, Joep, Volkers, Adriaan G., Boekel, Laura, Wolbink, Gerrit J., van der Kooi, Anneke J., Raaphorst, Joost, Löwenberg, Mark, Takkenberg, R. Bart, D'Haens, Geert R.A.M., Spuls, Phyllis I., Bekkenk, Marcel W., Musters, Annelie H., Post, Nicoline F., Bosma, Angela L., Hilhorst, Marc L., Vegting, Yosta, Bemelman, Frederike J., Voskuyl, Alexandre E., Broens, Bo, Sanchez, Agner Parra, van Els, Cécile A.C.M., de Wit, Jelle, Rutgers, Abraham, de Leeuw, Karina, Horváth, Barbara, Verschuuren, Jan J.G.M., Ruiter, Annabel M., van Ouwerkerk, Lotte, van der Woude, Diane, Allaart, Renée C.F., Teng, Y. K.Onno, van Paassen, Pieter, Busch, Matthias H., Jallah, Papay B.P., Brusse, Esther, van Doorn, Pieter A., Baars, Adája E., Hijnen, Dirk Jan, Schreurs, Corine R.G., van der Pol, W. Ludo, Goedee, H. Stephan, Steenhuis, Maurice, Keijzer, Sofie, Keijser, Jim B.D., the T2B! Immunity against SARS-CoV-2 study group, Neurologen, Brain, van Dam, Koos P.J., Wieske, Luuk, Stalman, Eileen W., Kummer, Laura Y.L., Roosen, Jesse, van Kempen, Zoé L.E., Killestein, Joep, Volkers, Adriaan G., Boekel, Laura, Wolbink, Gerrit J., van der Kooi, Anneke J., Raaphorst, Joost, Löwenberg, Mark, Takkenberg, R. Bart, D'Haens, Geert R.A.M., Spuls, Phyllis I., Bekkenk, Marcel W., Musters, Annelie H., Post, Nicoline F., Bosma, Angela L., Hilhorst, Marc L., Vegting, Yosta, Bemelman, Frederike J., Voskuyl, Alexandre E., Broens, Bo, Sanchez, Agner Parra, van Els, Cécile A.C.M., de Wit, Jelle, Rutgers, Abraham, de Leeuw, Karina, Horváth, Barbara, Verschuuren, Jan J.G.M., Ruiter, Annabel M., van Ouwerkerk, Lotte, van der Woude, Diane, Allaart, Renée C.F., Teng, Y. K.Onno, van Paassen, Pieter, Busch, Matthias H., Jallah, Papay B.P., Brusse, Esther, van Doorn, Pieter A., Baars, Adája E., Hijnen, Dirk Jan, Schreurs, Corine R.G., van der Pol, W. Ludo, Goedee, H. Stephan, Steenhuis, Maurice, Keijzer, Sofie, Keijser, Jim B.D., and the T2B! Immunity against SARS-CoV-2 study group

Published
2023

6. Primary SARS-CoV-2 infection in patients with immune-mediated inflammatory diseases:long-term humoral immune responses and effects on disease activity

Author

van Dam, Koos P.J., Volkers, Adriaan G., Wieske, Luuk, Stalman, Eileen W., Kummer, Laura Y.L., van Kempen, Zoé L.E., Killestein, Joep, Tas, Sander W., Boekel, Laura, Wolbink, Gerrit J., van der Kooi, Anneke J., Raaphorst, Joost, Takkenberg, R. Bart, D’Haens, Geert R.A.M., Spuls, Phyllis I., Bekkenk, Marcel W., Musters, Annelie H., Post, Nicoline F., Bosma, Angela L., Hilhorst, Marc L., Vegting, Yosta, Bemelman, Frederike J., Voskuyl, Alexandre E., Broens, Bo, Sanchez, Agner Parra, van Els, Cécile A.C.M., de Wit, Jelle, Rutgers, Abraham, de Leeuw, Karina, Horváth, Barbara, Verschuuren, Jan J.G.M., Ruiter, Annabel M., van Ouwerkerk, Lotte, van der Woude, Diane, Allaart, Renée C.F., Teng, Y. K.Onno, van Paassen, Pieter, Busch, Matthias H., Jallah, Papay B.P., Brusse, Esther, van Doorn, Pieter A., Baars, Adája E., Hijnen, Dirk Jan, Schreurs, Corine R.G., van der Pol, W. Ludo, Goedee, H. Stephan, Steenhuis, Maurice, Keijzer, Sofie, Keijser, Jim B.D., Cristianawati, Olvi, Eftimov, Filip, van Dam, Koos P.J., Volkers, Adriaan G., Wieske, Luuk, Stalman, Eileen W., Kummer, Laura Y.L., van Kempen, Zoé L.E., Killestein, Joep, Tas, Sander W., Boekel, Laura, Wolbink, Gerrit J., van der Kooi, Anneke J., Raaphorst, Joost, Takkenberg, R. Bart, D’Haens, Geert R.A.M., Spuls, Phyllis I., Bekkenk, Marcel W., Musters, Annelie H., Post, Nicoline F., Bosma, Angela L., Hilhorst, Marc L., Vegting, Yosta, Bemelman, Frederike J., Voskuyl, Alexandre E., Broens, Bo, Sanchez, Agner Parra, van Els, Cécile A.C.M., de Wit, Jelle, Rutgers, Abraham, de Leeuw, Karina, Horváth, Barbara, Verschuuren, Jan J.G.M., Ruiter, Annabel M., van Ouwerkerk, Lotte, van der Woude, Diane, Allaart, Renée C.F., Teng, Y. K.Onno, van Paassen, Pieter, Busch, Matthias H., Jallah, Papay B.P., Brusse, Esther, van Doorn, Pieter A., Baars, Adája E., Hijnen, Dirk Jan, Schreurs, Corine R.G., van der Pol, W. Ludo, Goedee, H. Stephan, Steenhuis, Maurice, Keijzer, Sofie, Keijser, Jim B.D., Cristianawati, Olvi, and Eftimov, Filip

Abstract

Background: Patients with immune-mediated inflammatory diseases (IMIDs) on immunosuppressants (ISPs) may have impaired long-term humoral immune responses and increased disease activity after SARS-CoV-2 infection. We aimed to investigate long-term humoral immune responses against SARS-CoV-2 and increased disease activity after a primary SARS-CoV-2 infection in unvaccinated IMID patients on ISPs. Methods: IMID patients on active treatment with ISPs and controls (i.e. IMID patients not on ISP and healthy controls) with a confirmed SARS-CoV-2 infection before first vaccination were included from an ongoing prospective cohort study (T2B! study). Clinical data on infections and increased disease activity were registered using electronic surveys and health records. A serum sample was collected before first vaccination to measure SARS-CoV-2 anti-receptor-binding domain (RBD) antibodies. Results: In total, 193 IMID patients on ISP and 113 controls were included. Serum samples from 185 participants were available, with a median time of 173 days between infection and sample collection. The rate of seropositive IMID patients on ISPs was 78% compared to 100% in controls (p < 0.001). Seropositivity rates were lowest in patients on anti-CD20 (40.0%) and anti-tumor necrosis factor (TNF) agents (60.5%), as compared to other ISPs (p < 0.001 and p < 0.001, respectively). Increased disease activity after infection was reported by 68 of 260 patients (26.2%; 95% CI 21.2–31.8%), leading to ISP intensification in 6 out of these 68 patients (8.8%). Conclusion: IMID patients using ISPs showed reduced long-term humoral immune responses after primary SARS-CoV-2 infection, which was mainly attributed to treatment with anti-CD20 and anti-TNF agents. Increased disease activity after SARS-CoV-2 infection was reported commonly, but was mostly mild. Trial registration: NL74974.018.20, Trial ID: NL8900. Register

Published
2023

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