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1.
Gastroenterology ; 162(7):S-278, 2022.
Article in English | EMBASE | ID: covidwho-1967264

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)

2.
Journal of Hospital Infection ; 122:180-186, 2022.
Article in English | Web of Science | ID: covidwho-1799838

ABSTRACT

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 patho-gens, 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 sequenc-ing is an emerging technology for culture-independent diagnosis of infection and anti-microbial 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. (c) 2022 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

3.
Embase; 2021.
Preprint in English | EMBASE | ID: ppcovidwho-330530

ABSTRACT

We investigated anti-spike IgG antibody responses and correlates of protection following second doses of ChAdOx1 or BNT162b2 SARS-CoV-2 vaccines in the UK general population. In 222,493 individuals, we found significant boosting of anti-spike IgG by second doses of both vaccines in all ages and using different dosing intervals, including the 3-week interval for BNT162b2. After second vaccination, BNT162b2 generated higher peak levels than ChAdOX1. Older individuals and males had lower peak levels with BNT162b2 but not ChAdOx1, while declines were similar across ages and sexes with ChAdOX1 or BNT162b2. Prior infection significantly increased antibody peak level and half-life with both vaccines. Anti-spike IgG levels were associated with protection from infection after vaccination and, to an even greater degree, after prior infection. At least 67% protection against infection was estimated to last for 2-3 months after two ChAdOx1 doses and 5-8 months after two BNT162b2 doses in those without prior infection, and 1-2 years for those unvaccinated after natural infection. A third booster dose may be needed, prioritised to ChAdOx1 recipients and those more clinically vulnerable.

4.
J Hosp Infect ; 122: 180-186, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1676812

ABSTRACT

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.


Subject(s)
COVID-19 , Cross Infection , COVID-19/prevention & control , Cross Infection/epidemiology , Cross Infection/microbiology , Cross Infection/prevention & control , Humans , Infection Control , Pandemics/prevention & control , SARS-CoV-2/genetics , Whole Genome Sequencing
5.
Clin Radiol ; 77(2): 148-155, 2022 02.
Article in English | MEDLINE | ID: covidwho-1611681

ABSTRACT

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.


Subject(s)
COVID-19/diagnostic imaging , Computed Tomography Angiography , SARS-CoV-2/genetics , Severity of Illness Index , Whole Genome Sequencing , Aged , COVID-19/mortality , COVID-19/virology , Cohort Studies , Critical Care , Female , Humans , Length of Stay , Male , Middle Aged , Retrospective Studies , Time Factors , United Kingdom , Viral Load
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