Combination therapy of infliximab and thiopurines, but not monotherapy with infliximab or vedolizumab, is associated with attenuated IgA and neutralisation responses to SARS-CoV-2 in inflammatory bowel disease

Wellens, Judith; Edmans, Matthew; Obolski, Uri; McGregor, Colleen GC; Simmonds, Peter; Turner, Marc; Jarvis, Lisa; Skelly, Donal; Dunachie, Susanna; Barnes, Eleanor; Eyre, David W; Colombel, Jean–Frédéric; Wong, Serre-Yu; Klenerman, Paul; Lindsay, James O.; Satsangi, Jack; Thompson, Craig

doi:10.1136/gutjnl-2021-326312

Cited by 4 publications

(9 citation statements)

References 11 publications

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“…We used a multi-spot assay system (Meso Scale Diagnostics [MSD] V-PLEX) to quantify total antibody responses to the SARS-CoV-2 nucleocapsid, the SARS-CoV-2 RBD, N-terminal domain (NTD) of the spike, the full-length spike, as well as the spike proteins of the 4 HCoVs and SARS-CoV-1 ( Figure 1 ) ( 26 ). In-house indirect enzyme-linked immunosorbent assays (ELISAs) were also developed for the SARS-CoV-2 RBD and full-length spike, in addition to the full-length alpha- and beta-HCoV spike proteins, to confirm the results produced by the MSD V-PLEX assay via a second independent method.…”

Section: Resultsmentioning

confidence: 99%

“…Three assays were run to determine neutralizing antibody responses: a pseudotyped SARS-CoV-2 microneutralization assay as well as 2 R-PLEX competition assays measuring the binding capacity of ACE2 to the SARS-CoV-2 spike and RBD, respectively ( Figure 3 ). The assays show entry inhibition, a widely used proxy for live virus SARS-CoV-2 neutralization capacity ( 24 , 26 , 30 ).…”

Section: Resultsmentioning

confidence: 99%

“…This could indicate that individuals admitted to an ICU with fatal outcomes had higher levels of immunity to HCoV-OC43 prior to SARS-CoV-2 infection than individuals admitted to an ICU with nonfatal outcomes ( Figure 5A ; ref. 26 ).…”

Section: Discussionmentioning

confidence: 99%

“…All standards and controls were run in duplicate. Data from the assay were analyzed using MSD Discovery Workbench software, which averaged all the duplicates, and generated and fitted all the data to standard curves ( 26 ).…”

Section: Methodsmentioning

confidence: 99%

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Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses

et al. 2022

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The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal outcomes with coronavirus disease 2019 (COVID-19) is that the immune response to the SARS-CoV-2 spike protein is enriched for antibodies directed against epitopes shared with endemic beta-coronaviruses and has a lower proportion of antibodies targeting the more protective variable regions of the spike. The magnitude of antibody responses to the SARS-CoV-2 full-length spike protein, its domains and subunits, and the SARS-CoV-2 nucleocapsid also correlated strongly with responses to the endemic beta-coronavirus spike proteins in individuals admitted to an intensive care unit (ICU) with fatal COVID-19 outcomes, but not in individuals with nonfatal outcomes. This correlation was found to be due to the antibody response directed at the S2 subunit of the SARS-CoV-2 spike protein, which has the highest degree of conservation between the beta-coronavirus spike proteins. Intriguingly, antibody responses to the less cross-reactive SARS-CoV-2 nucleocapsid were not significantly different in individuals who were admitted to an ICU with fatal and nonfatal outcomes, suggesting an antibody profile in individuals with fatal outcomes consistent with an “original antigenic sin” type response.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses

et al. 2022

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“…Wellens et al. measured the IgG and IgA production against the receptor binding domain (RBD) of the SARS-CoV-2 spike, full-length spike (S) and the nucleocapsid (N) in patients with IBD and SARS-CoV-2 infection treated with either infliximab or vedolizumab monotherapy, or infliximab/thiopurine combination therapy ( 50 ). Moreover, neutralizing SARS-CoV-2 antibodies were evaluated.…”

Section: Immune Response Of Patients With Inflammatory Bowel Disease ...mentioning

confidence: 99%

Risks of SARS-CoV-2 Infection and Immune Response to COVID-19 Vaccines in Patients With Inflammatory Bowel Disease: Current Evidence

Esposito

Caminiti

Giordano³

et al. 2022

Front. Immunol.

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Inflammatory bowel diseases (IBD), including Crohn’s disease, ulcerative colitis, and unclassified inflammatory bowel disease, are a group of chronic, immune mediated conditions that are presumed to occur in genetically susceptible individuals because of a dysregulated intestinal immune response to environmental factors. IBD patients can be considered subjects with an aberrant immune response that makes them at increased risk of infections, particularly those due to opportunistic pathogens. In many cases this risk is significantly increased by the therapy they receive. Aim of this narrative review is to describe the impact of SARS-CoV-2 infection and the immunogenicity of COVID-19 vaccines in patients with IBD. Available data indicate that patients with IBD do not have an increased susceptibility to infection with SARS-CoV-2 and that, if infected, in the majority of the cases they must not modify the therapy in place because this does not negatively affect the COVID-19 course. Only corticosteroids should be reduced or suspended due to the risk of causing severe forms. Furthermore, COVID-19 seems to modify the course of IBD mainly due to the impact on intestinal disease of the psychological factors deriving from the measures implemented to deal with the pandemic. The data relating to the immune response induced by SARS-CoV-2 or by COVID-19 vaccines can be considered much less definitive. It seems certain that the immune response to disease and vaccines is not substantially different from that seen in healthy subjects, with the exception of patients treated with anti-tumor necrosis factor alone or in combination with other immunosuppressants who showed a reduced immune response. How much, however, this problem reduces induced protection is not known. Moreover, the impact of SARS-CoV-2 variants on IBD course and immune response to SARS-CoV-2 infection and COVID-19 vaccines has not been studied and deserves attention. Further studies capable of facing and solving unanswered questions are needed in order to adequately protect IBD patients from the risks associated with SARS-CoV-2 infection.

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Cytokine signature in convalescent SARS-CoV-2 patients with inflammatory bowel disease receiving vedolizumab

Dallari,

Martinez Pazos,

Munoz Eusse

et al. 2024

Sci Rep

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While differential antibody responses SARS-CoV-2 in patients with inflammatory bowel disease (IBD) receiving infliximab and vedolizumab are well-characterized, the immune pathways underlying these differences remain unknown. Prior to COVID-19 vaccine development, we screened 235 patients with IBD receiving biological therapy for antibodies to SARS-CoV-2 and measured serum cytokines. In seropositive patients, we prospectively collected clinical data. We found a cytokine signature in patients receiving vedolizumab who are seropositive compared with seronegative for SARS-CoV-2 antibodies that may be linked to repeated SARS-CoV-2 infections. However, there were no differences between seropositive and seronegative patients receiving infliximab. In this single-center cohort of patients with IBD with anti-SARS-CoV-2 antibodies at the onset of the COVID-19 pandemic, and therefore without influence of vaccination, there is a cytokine signature in patients receiving vedolizumab but not infliximab. These findings lay the groundwork for further studies on immune consequences of viral infection in patients with IBD, which is postulated to evolve from aberrant host-microbe responses.

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Combination therapy of infliximab and thiopurines, but not monotherapy with infliximab or vedolizumab, is associated with attenuated IgA and neutralisation responses to SARS-CoV-2 in inflammatory bowel disease

Cited by 4 publications

References 11 publications

Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses

Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses

Risks of SARS-CoV-2 Infection and Immune Response to COVID-19 Vaccines in Patients With Inflammatory Bowel Disease: Current Evidence

Cytokine signature in convalescent SARS-CoV-2 patients with inflammatory bowel disease receiving vedolizumab

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