BOTH VEDOLIZUMAB AND ANTI-TNF THERAPY ARE ASSOCIATED WITH ATTENUATION OF SEROLOGICAL AND NEUTRALIZING RESPONSES TO SARS-COV-2 INFECTION IN INFLAMMATORY BOWEL DISEASE

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)

Infection prevention and control insights from a decade of pathogen whole-genome sequencing.

Pathogen whole-genome sequencing has become an important tool for understanding the transmission and epidemiology of infectious diseases. It has improved our understanding of sources of infection and transmission routes for important healthcare-associated pathogens, including Clostridioides difficile and Staphylococcus aureus. Transmission from known infected or colonized patients in hospitals may explain fewer cases than previously thought and multiple introductions of these pathogens from the community may play a greater a role. The findings have had important implications for infection prevention and control. Sequencing has identified heterogeneity within pathogen species, with some subtypes transmitting and persisting in hospitals better than others. It has identified sources of infection in healthcare-associated outbreaks of food-borne pathogens, Candida auris and Mycobacterium chimera, as well as individuals or groups involved in transmission and historical sources of infection. SARS-CoV-2 sequencing has been central to tracking variants during the COVID-19 pandemic and has helped understand transmission to and from patients and healthcare workers despite prevention efforts. Metagenomic sequencing is an emerging technology for culture-independent diagnosis of infection and antimicrobial resistance. In future, sequencing is likely to become more accessible and widely available. Real-time use in hospitals may allow infection prevention and control teams to identify transmission and to target interventions. It may also provide surveillance and infection control benchmarking. Attention to ethical and wellbeing issues arising from sequencing identifying individuals involved in transmission is important. Pathogen whole-genome sequencing has provided an incredible new lens to understand the epidemiology of healthcare-associated infection and to better control and prevent these infections.

Parenchymal involvement on CT pulmonary angiography in SARS-CoV-2 Alpha variant infection and correlation of COVID-19 CT severity score with clinical disease severity and short-term prognosis in a UK cohort.

AIM: To determine if there is a difference in radiological, biochemical, or clinical severity between patients infected with Alpha-variant SARS-CoV-2 compared with those infected with pre-existing strains, and to determine if the computed tomography (CT) severity score (CTSS) for COVID-19 pneumonitis correlates with clinical severity and can prognosticate outcomes. MATERIALS AND METHODS: Blinded CTSS scoring was applied to 137 hospital patients who had undergone both CT pulmonary angiography (CTPA) and whole-genome sequencing of SARS-CoV-2 within 14 days of CTPA between 1/12/20-5/1/21. RESULTS: There was no evidence of a difference in imaging severity on CTPA, viral load, clinical parameters of severity, or outcomes between Alpha and preceding variants. CTSS on CTPA strongly correlates with clinical and biochemical severity at the time of CTPA, and with patient outcomes. Classifying CTSS into a binary value of "high" and "low", with a cut-off score of 14, patients with a high score have a significantly increased risk of deterioration, as defined by subsequent admission to critical care or death (multivariate hazard ratio [HR] 2.76, p<0.001), and hospital length of stay (17.4 versus 7.9 days, p<0.0001). CONCLUSION: There was no evidence of a difference in radiological severity of Alpha variant infection compared with pre-existing strains. High CTSS applied to CTPA is associated with increased risk of COVID-19 severity and poorer clinical outcomes and may be of use particularly in settings where CT is not performed for diagnosis of COVID-19 but rather is used following clinical deterioration.