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1.
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.

2.
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.

3.
Journal of Crohn's and Colitis ; 16:i069-i070, 2022.
Article in English | EMBASE | ID: covidwho-1722298

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.

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
6.
Antimicrobial Resistance and Infection Control ; 10(SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1448382

ABSTRACT

Introduction: A better understanding of the relative importance of different transmission pathways of SARS-CoV-2 in hospital settings has the potential to help improve targeting of control measures aimed at reducing nosocomial spread. Objectives: To quantify the associations between risks of nosocomial SARS-CoV-2 infection and exposure on the same ward to infected healthcare workers (HCWs), to patients likely to have been infected nosocomially, and to patients with community onset COVID-19. Methods: Ward-level data were collected from four teaching hospitals in Oxfordshire, UK, over an 8 month period in 2020. SARS-CoV-2 infections were identified using both PCR results from symptomatic and asymptomatic testing and serological data coupled with symptom recall. A series of statistical models were used to quantify associations between exposures and probable hospital transmission events. Results: Risk to patients of probable nosocomial acquisition was most strongly associated with exposure to other patients with hospitalacquired SARS-CoV-2 (aOR, 1.76, 95%CI 1.51, 2.04), followed by the presence of an infected HCW on the same ward (aOR 1.45, 95%CI 1.22,1.71). The association with patients with community onset COVID- 19 was weaker (aOR 1.12, 95%CI 0.96,1.26). Transmission to HCWs was associated with exposure to other infectious HCWs and patients with hospital-acquired SARS-CoV-2 (aOR 1.66, 95%CI 1.55,1.78 and aOR 1.45, 95%CI 1.32,1.58 respectively). The introduction of more stringent infection prevention and control measures which included testing all patients for SARS-CoV-2 by PCR on admission and at weekly intervals was associated with substantial reduction in transmission risk to both patients (adjusted odds ratio, aOR 0.25, 95%CI 0.14, 0.42) and HCWs (aOR 0.43, 95%CI 0.34, 0.53). Conclusion: Patients who acquired SARS-CoV-2 in the hospital and, to a lesser degree, infectious HCWs likely working prior to the onset of symptoms, were the most strongly associated with increased risk of SARSCoV- 2 transmission. In contrast, exposure to patients who had acquired SARS-CoV-2 in the community was associated with, at most, modest increases in the daily risk of infection for both healthcare staff and the other patients.

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