DOP20 Functional viral neutralisation responses after SARS-CoV-2 infection in Inflammatory Bowel Disease patients receiving infusion therapies: Report from the ICARUS-IBD Consortium
Wellens, J.(1,2);Edmans, M.(3);Obolski, U.(4,5);Marlow, L.(1);Brann, S.(1);Dunachie, S.(3,6,7);Eyre, D.(8,9);Helmus, D.(10);Barnes, E.(1,3);Colombel, J.F.(10);Wong, S.Y.(10);Klenerman, P.(1,3);Lindsay, J.O.(11,12);Thompson, C.P.(13);Satsangi, J.(1);
(1)University of Oxford, Translational Gastro-Intestinal Unit- Nuffield Department of Medicine, Oxford, United Kingdom;(2)University hospitals Leuven, Translational Research for Gastrointestinal Diseases, Leuven, Belgium;(3)University of Oxford, Peter Medawar Building for Pathogen Research, Oxford, United Kingdom;(4)Tel-Aviv University, Porter School of Environmental and Earth Sciences- Faculty of Exact Sciences, Tel-Aviv, Israel;(5)Tel-Aviv University, School of Public Health- Faculty of Medicine, Tel-Aviv, Israel;(6)Oxford University Hospitals- NHS, Department of Microbiology/Infectious Diseases, Oxford, United Kingdom;(7)University of Oxford, Centre for Tropical Medicine and Global Health- Nuffield Department of Medicine, Oxford, United Kingdom;(8)University of Oxford, Big Data Institute, Oxford, United Kingdom;(9)University of Oxford, Infectious Diseases & Medical Microbiology, Oxford, United Kingdom;(10)Icahn School of Medicine at Mount Sinai- New York, The Henry D. Janowitz Division of Gastroenterology- Department of Medicine, New York, United States;(11)The Royal London Hospital, Barts Health NHS Trust- department of Gastroenterology, London, United Kingdom;(12)Blizard Institute- Barts and the London School of Medicine Queen Mary University of London, Centre for Immunobiology, London, United Kingdom;(13)University of Oxford, Department of Zoology, Oxford, United Kingdom; The ICARUS-IBD CONSORTIUM
Background
Recent data have highlighted adverse clinical outcomes in IBD patients treated with infliximab/thiopurines (IFX/THIO) upon infection with SARS-CoV-2, as well as attenuated serological responses after infection and vaccination in patients treated with IFX. To provide mechanistic insight, we explored the serological and functional anti-viral response after infection in IBD patients treated with VDZ, IFX or IFX/THIO compared to healthy controls to guide clinical decision-making regarding treatment and vaccination strategies.
Methods
Serum from 640 IBD patients attending routine infusions in Oxford and London in May to December 2020 was screened for anti-SARS-CoV-2 antibody responses by the Abbott assay. Serum from seropositive patients was compared to seropositive health care workers (Table 1). Antibody reactivity to the SARS-CoV-2 wild type strain receptor-binding domain (RBD), full-length spike, and nucleocapsid was assayed by IgG/IgA ELISA over time as well as by IgG high-throughput MSD V-PLEX ELISA at the time of seropositivity. A pseudotyped SARS-CoV-2 virus microneutralization assay was used to detect neutralising antibodies to the wild type, and an ELISA-based inhibition assay to compare differential inhibition of the wild type vs. delta variant SARS-CoV-2 RBD-ACE2 interaction.
Results
All IBD patients showed significantly reduced IgG antibody responses compared to healthy controls for all SARS-CoV-2 antigens, using MSD V-PLEX ELISA (Figure 1). The greatest reduction in IgG response by ELISA was observed in individuals treated with IFX/THIO (p=0.00019), whereas IgG response over time declined significantly faster in the IFX treated group (p=0.019). IgA responses were significantly reduced in the IFX/THIO group compared to healthy controls (p=0.009), but not in the IFX or VDZ monotherapy group. The rate of decline in these monotherapy groups was also not significantly different to healthy controls. Functional SARS-CoV-2 neutralisation was significantly lower in all IBD patients compared to healthy controls, with the greatest reduction in patients receiving IFX/THIO (Figure 2A; p=0.00000091). The delta variant inhibition capacity was significantly reduced in 68.1% of IBD patients (30/44, Figure 2B; p=0.0005).
Conclusion
IFX/THIO is associated with significantly lower IgA and IgG responses, and with impaired functional SARS-CoV-2 neutralising antibody capacity, compared to healthy individuals. Whilst IgG and neutralisation responses are reduced in each group of IBD patients, these findings were most pronounced in the combination treatment group. As neutralising antibody responses are associated with protection, this observation may impact on decision-making regarding treatment and vaccination/antiviral strategies.