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

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

doi:10.1186/s12879-023-08298-6

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

Koos P. J. G. van Dam, Adriaan Volkers, Luuk W. Wieske, Eileen Stalman, Laura Y. L. Kummer, Zoe L. E. van Kempen, Joep W. Killestein, Sander Tas, Laura J. Boekel, Gerrit J. Wolbink, Anneke van der Kooi, Joost Raaphorst, R. Bart Takkenberg, Geert R. A. M. I. D'Haens, Phyllis W. Spuls, Marcel H. Bekkenk, Annelie F. Musters, Nicoline L. Post, Angela L. Bosma, Marc HilhorstYosta J. Vegting, Frederike E. Bemelman, Alexandre Voskuyl, Bo Broens, Agner Parra Sanchez, Cecile A. C. M. van Els, Jelle de Wit, Abraham Rutgers, Karina de Leeuw, Barbara Horvath, Jan J. G. M. M. Verschuuren, Annabel Ruiter, Lotte van Ouwerkerk, Diane van der Woude, Renee C. F. Allaart, Y. K. Onno Teng, Pieter H. van Paassen, Matthias Busch, Papay B. P. Jallah, Esther A. Brusse, Pieter van Doorn, Adaja E. Baars, Dirk Jan Hijnen, Corine R. G. Schreurs, W. Ludo van der Pol, H. Stephan Goedee, Maurice Steenhuis, Sofie Keijzer, Jim B. D. Keijser, Olvi Cristianawati, Filip Eftimov^*, T2B! immunity against SARS-CoV-2 study group

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BackgroundPatients 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.MethodsIMID 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.ResultsIn 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%).ConclusionIMID 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.

Original language	English
Article number	332
Number of pages	11
Journal	BMC Infectious Diseases
Volume	23
Issue number	1
DOIs	https://doi.org/10.1186/s12879-023-08298-6
Publication status	Published - 17 May 2023

Keywords

SARS-CoV-2
Covid-19
Autoimmune disease
Immune-mediated inflammatory diseases
Immunosuppression
TNF
Immunity
Antibodies
Disease activity
Flare
ANTIBODIES

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van Dam, K. P. J. G., Volkers, A., Wieske, L. W., Stalman, E., Kummer, L. Y. L., van Kempen, Z. L. E., Killestein, J. W., Tas, S., Boekel, L. J., Wolbink, G. J., van der Kooi, A., Raaphorst, J., Takkenberg, R. B., D'Haens, G. R. A. M. I., Spuls, P. W., Bekkenk, M. H., Musters, A. F., Post, N. L., Bosma, A. L., ... T2B! immunity against SARS-CoV-2 study group (2023). Primary SARS-CoV-2 infection in patients with immune-mediated inflammatory diseases: long-term humoral immune responses and effects on disease activity. BMC Infectious Diseases, 23(1), Article 332. https://doi.org/10.1186/s12879-023-08298-6

@article{34b081aa304040a1a8c1c7eec815bcf0,

title = "Primary SARS-CoV-2 infection in patients with immune-mediated inflammatory diseases: long-term humoral immune responses and effects on disease activity",

abstract = "BackgroundPatients 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.MethodsIMID 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.ResultsIn 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%).ConclusionIMID 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.",

keywords = "SARS-CoV-2, Covid-19, Autoimmune disease, Immune-mediated inflammatory diseases, Immunosuppression, TNF, Immunity, Antibodies, Disease activity, Flare, ANTIBODIES",

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

year = "2023",

month = may,

day = "17",

doi = "10.1186/s12879-023-08298-6",

language = "English",

volume = "23",

journal = "BMC Infectious Diseases",

issn = "1471-2334",

publisher = "BioMed Central Ltd",

number = "1",

}

van Dam, KPJG, Volkers, A, Wieske, LW, Stalman, E, Kummer, LYL, van Kempen, ZLE, Killestein, JW, Tas, S, Boekel, LJ, Wolbink, GJ, van der Kooi, A, Raaphorst, J, Takkenberg, RB, D'Haens, GRAMI, Spuls, PW, Bekkenk, MH, Musters, AF, Post, NL, Bosma, AL, Hilhorst, M, Vegting, YJ, Bemelman, FE, Voskuyl, A, Broens, B, Sanchez, AP, van Els, CACM, de Wit, J, Rutgers, A, de Leeuw, K, Horvath, B, Verschuuren, JJGMM, Ruiter, A, van Ouwerkerk, L, van der Woude, D, Allaart, RCF, Teng, YKO, van Paassen, PH, Busch, M, Jallah, PBP, Brusse, EA, van Doorn, P, Baars, AE, Hijnen, DJ, Schreurs, CRG, van der Pol, WL, Goedee, HS, Steenhuis, M, Keijzer, S, Keijser, JBD, Cristianawati, O, Eftimov, F & T2B! immunity against SARS-CoV-2 study group 2023, 'Primary SARS-CoV-2 infection in patients with immune-mediated inflammatory diseases: long-term humoral immune responses and effects on disease activity', BMC Infectious Diseases, vol. 23, no. 1, 332. https://doi.org/10.1186/s12879-023-08298-6

TY - JOUR

T1 - Primary SARS-CoV-2 infection in patients with immune-mediated inflammatory diseases: long-term humoral immune responses and effects on disease activity

AU - van Dam, Koos P. J. G.

AU - Volkers, Adriaan

AU - Wieske, Luuk W.

AU - Stalman, Eileen

AU - Kummer, Laura Y. L.

AU - van Kempen, Zoe L. E.

AU - Killestein, Joep W.

AU - Tas, Sander

AU - Boekel, Laura J.

AU - Wolbink, Gerrit J.

AU - van der Kooi, Anneke

AU - Raaphorst, Joost

AU - Takkenberg, R. Bart

AU - D'Haens, Geert R. A. M. I.

AU - Spuls, Phyllis W.

AU - Bekkenk, Marcel H.

AU - Musters, Annelie F.

AU - Post, Nicoline L.

AU - Bosma, Angela L.

AU - Hilhorst, Marc

AU - Vegting, Yosta J.

AU - Bemelman, Frederike E.

AU - Voskuyl, Alexandre

AU - Broens, Bo

AU - Sanchez, Agner Parra

AU - van Els, Cecile A. C. M.

AU - de Wit, Jelle

AU - Rutgers, Abraham

AU - de Leeuw, Karina

AU - Horvath, Barbara

AU - Verschuuren, Jan J. G. M. M.

AU - Ruiter, Annabel

AU - van Ouwerkerk, Lotte

AU - van der Woude, Diane

AU - Allaart, Renee C. F.

AU - Teng, Y. K. Onno

AU - van Paassen, Pieter H.

AU - Busch, Matthias

AU - Jallah, Papay B. P.

AU - Brusse, Esther A.

AU - van Doorn, Pieter

AU - Baars, Adaja E.

AU - Hijnen, Dirk Jan

AU - Schreurs, Corine R. G.

AU - van der Pol, W. Ludo

AU - Goedee, H. Stephan

AU - Steenhuis, Maurice

AU - Keijzer, Sofie

AU - Keijser, Jim B. D.

AU - Cristianawati, Olvi

AU - Eftimov, Filip

AU - T2B! immunity against SARS-CoV-2 study group

PY - 2023/5/17

Y1 - 2023/5/17

N2 - BackgroundPatients 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.MethodsIMID 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.ResultsIn 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%).ConclusionIMID 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.

AB - BackgroundPatients 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.MethodsIMID 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.ResultsIn 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%).ConclusionIMID 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.

KW - SARS-CoV-2

KW - Covid-19

KW - Autoimmune disease

KW - Immune-mediated inflammatory diseases

KW - Immunosuppression

KW - TNF

KW - Immunity

KW - Antibodies

KW - Disease activity

KW - Flare

KW - ANTIBODIES

U2 - 10.1186/s12879-023-08298-6

DO - 10.1186/s12879-023-08298-6

M3 - Article

C2 - 37198536

SN - 1471-2334

VL - 23

JO - BMC Infectious Diseases

JF - BMC Infectious Diseases

IS - 1

M1 - 332

ER -