ABSTRACT
Introduction: Vaccines prevent severe disease, but to prevent viral transmission and lessen the risk of new variants emerging they need to also enhance mucosal protection. Intramuscular (IM) vaccines induce systemic antibody and appear to transiently reduce transmission, but their effect on nasal antibody in previously infected subjects has not been studied. Aim(s): To study durability of local and systemic antibody responses after COVID-19 in those subsequently vaccinated. Method(s): Nasal fluid and plasma were collected from 448 hospitalised COVID-19 cases during admission and convalescence via the ISARIC4C/PHOSP-COVID studies. IgA/G to wildtype SARS-CoV-2 S, NP and to receptor binding domain (RBD) of Delta and Omicron variants were measured by ELISA. Result(s): Nasal IgA/G anti-S/RBD responses appeared within 28 days and remained high for 1 year(figure 1). Plasma IgA/G responses to S also remained elevated at 1 year(P<0.001). 87% of those with complete data were vaccinated between 6-12 months after infection;when nasal and plasma anti-NP IgA/G waned, whilst anti-S/RBD responses to Delta and Omicron were maintained or increased. Conclusion(s): This is the first study to demonstrate that IM vaccination may boost nasal antibody 1 year after COVID19. This may explain why IM vaccination reduces transmission, adding to the evidence for booster vaccines in COVID-19 recoverees. (Figure Presented).
ABSTRACT
Introduction: More adverse clinical outcomes following SARS-CoV-2 infection are reported in patients treated with infliximab/thiopurines (IFX/THIO), compared with biological monotherapy with anti-TNF or vedolizumab (VDZ). VDZ has been associated with a heightened and more durable serological response after infection and vaccination, compared to IFX. However, whether IBD patients on VDZ have a fully intact systemic response to SARS- CoV2 remains unknown. We explored the serological and functional neutralizing response after SARS-CoV-2 infection in IBD patients treated with VDZ, IFX or IFX/THIO compared to true healthy controls to guide treatment decisions and vaccination strategies. Methods: Serum from 640 IBD patients attending routine infusions in Oxford and London (May to December 2020) was screened by the Abbott assay for SARS-CoV-2 nucleocapsid (N) antibodies. Serum from seropositive patients was compared to seropositive health care workers (Table 1). Antibody reactivity to the SARS-CoV-2 wild type (WT) strain receptor-binding domain (RBD), full-length spike, and N was assayed by IgG/IgA ELISA over time as well as by IgG MSD V-PLEX ELISA at the time of seropositivity. A pseudotyped SARS-CoV-2 virus microneutralization assay was used to detect neutralizing antibodies to the WT, and an ELISA-based inhibition assay to compare differential inhibition of the WT vs. delta variant (DV) SARS-CoV-2 RBD-ACE2 interaction. Results: All IBD patients showed significantly reduced IgG antibody responses compared to healthy controls to all SARS-CoV-2 antigens, using MSD V-PLEX (Figure 1A-C). The greatest reduction in IgG response by ELISA was observed in patients 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 group. The rate of decline in these monotherapy groups was not significantly different to healthy controls. Compared to healthy controls, functional SARS-CoV-2 neutralization was reduced in each treatment group (Figure 1D), with the greatest effect in patients receiving IFX/THIO (p=0.00000091). Neutralizing capacity to the DV was significantly reduced in 68.1% of IBD patients (30/44, p=0.0005). Conclusion: Both IFX and VDZ are associated with significantly reduced IgG responses to multiple SARS-CoV-2 antigens, and with impaired functional SARS-CoV-2 neutralizing antibody capacity, compared to healthy individuals. However, whilst IgG and neutralization responses are reduced in IBD patients on biological monotherapy, these findings were most pronounced in the combination treatment group. As neutralizing antibody responses are associated with protection, these observations may impact on decision-making regarding treatment and vaccination strategies.(Table Presented)(Figure Presented)
ABSTRACT
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.