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Publications (85)
The UK Health Security Agency (UKHSA) is working with the Animal and Plant Health Agency (APHA) and the Department for Environment, Food and Rural Affairs (Defra) to investigate the risk to human health of avian influenza (influenza A H5N1) in England. This briefing is produced to share data useful to other public health investigators and academic...
Complement, a critical defence against pathogens, has been implicated as a driver of pathology in COVID-19. Complement activation products are detected in plasma and tissues and complement blockade considered for therapy. To delineate roles of complement in immunopathogenesis, we undertook the largest comprehensive study of complement in an COVID-1...
The Omicron variant of SARS-CoV-2 became the globally dominant variant in early 2022. A sub-lineage of the Omicron variant (BA.2) was identified in England in January 2022. Here, we investigated hospitalisation and mortality risks of COVID-19 cases with the Omicron sub-lineage BA.2 (n = 258,875) compared to BA.1 (n = 984,337) in a large cohort stud...
The first SARS-CoV-2 variant of concern (VOC) to be designated was lineage B.1.1.7, later labelled by the World Health Organization as Alpha. Originating in early autumn but discovered in December 2020, it spread rapidly and caused large waves of infections worldwide. The Alpha variant is notable for being defined by a long ancestral phylogenetic b...
The SARS-CoV-2 Delta variant of concern spread globally, causing resurgences of COVID-19 worldwide1,2. Delta’s emergence in the UK occurred on the background of a heterogeneous landscape of immunity and relaxation of non-pharmaceutical interventions. Here we analyse 52,992 virus genomes from England together with 93,649 global genomes to reconstruc...
Following the report of an excess in paediatric cases of severe acute hepatitis of unknown aetiology by the United Kingdom (UK) on 5 April 2022, 427 cases were reported from 20 countries in the World Health Organization European Region to the European Surveillance System TESSy from 1 January 2022 to 16 June 2022. Here, we analysed demographic, epid...
Since the first reports of hepatitis of unknown aetiology occurring in UK children, over 1000 cases have been reported worldwide, including 268 cases in the UK, with the majority younger than 6 years old. Using genomic, proteomic and immunohistochemical methods, we undertook extensive investigation of 28 cases and 136 control subjects. In five case...
Since the first reports of hepatitis of unknown aetiology occurring in UK children, over 1000 cases have been reported worldwide, including 268 cases in the UK, with the majority younger than 6 years old. Using genomic, proteomic and immunohistochemical methods, we undertook extensive investigation of 28 cases and 136 control subjects. In five case...
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An outbreak of acute hepatitis of unknown aetiology in children was first reported in Scotland in April 2022. ¹ Cases aged <16 years have since been identified in 35 countries. ² Here we report a detailed investigation of 9 early cases and 58 control subjects. Using next-generation sequencing and real-time PCR, adeno-associated virus 2 (A...
Some COVID-19 patients are unable to clear their infection or are at risk of severe disease, requiring treatment with neutralising monoclonal antibodies (nmAb) and/or antivirals. The rapid roll-out of novel therapeutics means there is limited understanding of the likely genetic barrier to drug resistance. Unprecedented genomic surveillance of SARS-...
Background:
Since the emergence of SARS-CoV-2, evolutionary pressure has driven large increases in the transmissibility of the virus. However, with increasing levels of immunity through vaccination and natural infection the evolutionary pressure will switch towards immune escape. Genomic surveillance in regions of high immunity is crucial in detec...
Introduction:
Understanding the effectiveness and durability of protection against SARS-CoV-2 infection conferred by previous infection and COVID-19 is essential to inform ongoing management of the pandemic. This study aims to determine whether prior SARS-CoV-2 infection or COVID-19 vaccination in healthcare workers protects against future infecti...
Between 7 and 25 May, 86 monkeypox cases were confirmed in the United Kingdom (UK). Only one case is known to have travelled to a monkeypox virus (MPXV) endemic country. Seventy-nine cases with information were male and 66 reported being gay, bisexual, or other men who have sex with men. This is the first reported sustained MPXV transmission in the...
Background
The emergence of the SARS-CoV-2 Alpha variant in England coincided with a rapid increase in the number of PCR-confirmed COVID-19 cases in areas where the variant was concentrated.
Aim
Our aim was to assess whether infection with Alpha was associated with more severe clinical outcomes than the wild type.
Methods
Laboratory-confirmed inf...
Admission procalcitonin measurements and microbiology results were available for 1040 hospitalized adults with coronavirus disease 2019 (from 48 902 included in the International Severe Acute Respiratory and Emerging Infections Consortium World Health Organization Clinical Characterisation Protocol UK study). Although procalcitonin was higher in ba...
Global sequencing and surveillance capacity for SARS-CoV-2 must be strengthened and combined with multidisciplinary studies of infectivity, virulence and immune escape, in order to track the unpredictable evolution of the ongoing COVID-19 pandemic.
COVID-19 is clinically characterised by fever, cough, and dyspnoea. Symptoms affecting other organ systems have been reported. However, it is the clinical associations of different patterns of symptoms which influence diagnostic and therapeutic decision-making. In this study, we applied clustering techniques to a large prospective cohort of hospita...
Background
Dexamethasone was the first intervention proven to reduce mortality in patients with COVID-19 being treated in hospital. We aimed to evaluate the adoption of corticosteroids in the treatment of COVID-19 in the UK after the RECOVERY trial publication on June 16, 2020, and to identify discrepancies in care.
Methods
We did an audit of clin...
The BA.1 sub-lineage of the Omicron (B.1.1.529) variant, first detected in the UK in mid-November 2021, rapidly became the dominant strain partly due to reduced vaccine effectiveness. An increase in a second Omicron sub-lineage BA.2 was observed in early January 2022. In this study we use a test-negative case control study design to estimate vaccin...
The first SARS-CoV-2 variant of concern (VOC) to be designated was lineage B.1.1.7, later labelled by the World Health Organisation (WHO) as Alpha. Originating in early Autumn but discovered in December 2020, it spread rapidly and caused large waves of infections worldwide. The Alpha variant is notable for being defined by a long ancestral phylogen...
Background:
A rapid increase in coronavirus disease 2019 (Covid-19) cases due to the omicron (B.1.1.529) variant of severe acute respiratory syndrome coronavirus 2 in highly vaccinated populations has aroused concerns about the effectiveness of current vaccines.
Methods:
We used a test-negative case-control design to estimate vaccine effectivene...
Background
The omicron variant (B.1.1.529) of SARS-CoV-2 has demonstrated partial vaccine escape and high transmissibility, with early studies indicating lower severity of infection than that of the delta variant (B.1.617.2). We aimed to better characterise omicron severity relative to delta by assessing the relative risk of hospital attendance, ho...
To investigate if the AY.4.2 sub-lineage of the SARS-CoV-2 Delta variant is associated with hospitalisation and mortality risks that differ from non-AY.4.2 Delta risks, we performed a retrospective cohort study of sequencing-confirmed COVID-19 cases in England based on linkage of routine healthcare datasets. Using stratified Cox regression, we esti...
Background:
The duration and effectiveness of immunity from infection with and vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are relevant to pandemic policy interventions, including the timing of vaccine boosters.
Methods:
We investigated the duration and effectiveness of immunity in a prospective cohort of asy...
On 5 January 2022, high pathogenicity avian influenza A(H5N1) was confirmed in an individual who kept a large flock of ducks at their home in England. The individual remained asymptomatic. H5N1 was confirmed in 19/20 sampled live birds on 22 December 2021. Comprehensive contact tracing (n = 11) revealed no additional primary cases or secondary tran...
Background
Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), have been used since December 2020 in the United Kingdom. Real-world data have shown the vaccines to be highly effective against Covid-19 and related severe disease and death. Vaccine effectiveness may...
The Delta variant of concern of SARS-CoV-2 has spread globally causing large outbreaks and resurgences of COVID-19 cases. The emergence of Delta in the UK occurred on the background of a heterogeneous landscape of immunity and relaxation of non-pharmaceutical interventions. Here we analyse 52,992 Delta genomes from England in combination with 93,64...
The evolution of the SARS-CoV-2 pandemic continuously produces new variants, which warrant timely epidemiological characterisation. Here we use the dense genomic surveillance generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June...
Background
A rapid increase in cases due to the SARS-CoV-2 Omicron (B.1.1.529) variant in highly vaccinated populations has raised concerns about the effectiveness of current vaccines.
Methods
We used a test-negative case-control design to estimate vaccine effectiveness (VE) against symptomatic disease caused by the Omicron and Delta variants in En...
The Delta variant of concern of SARS-CoV-2 has spread globally causing large outbreaks and resurgences of COVID-19 cases. The emergence of Delta in the UK occurred on the background of a heterogeneous landscape of immunity and relaxation of non-pharmaceutical interventions. Here we analyse 52,992 Delta genomes from England in combination with 93,64...
Background
Predicting bed occupancy for hospitalised patients with COVID-19 requires understanding of length of stay (LoS) in particular bed types. LoS can vary depending on the patient’s “bed pathway” - the sequence of transfers of individual patients between bed types during a hospital stay. In this study, we characterise these pathways, and thei...
Vaccination and disease
The United Kingdom has high rates of vaccination for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exceeding 80% of adults. As immunity wanes and social distancing is relaxed, how are rates of illness and severe disease affected by more infectious variants? Elliott et al . used reverse transcription PCR data...
Background:
Previous infection with SARS-CoV-2 affects the immune response to the first dose of the SARS-CoV-2 vaccine. We aimed to compare SARS-CoV-2-specific T-cell and antibody responses in health-care workers with and without previous SARS-CoV-2 infection following a single dose of the BNT162b2 (tozinameran; Pfizer-BioNTech) mRNA vaccine.
Met...
Background
Acute kidney injury (AKI) is common in COVID-19. This study investigated adults hospitalised with COVID-19 and hypothesised that risk factors for AKI would include co-morbidities and non-white race.
Methods
A prospective multicentre cohort study was performed using patients admitted to 254 UK hospitals with COVID-19 between January 17th...
The bat connection
The heterogeneity of COVID-19 makes it challenging to predict the course of infection in an individual. Upon virus infection, interferons (IFNs) generate the initial signals for cellular defenses. Knowing that defects in IFN signaling are associated with more severe COVID-19, Wickenhagen et al . used IFN-stimulated gene expressio...
Background
COVID-19 vaccines have been used for 9 months in the UK. Real world data have demonstrated the vaccines to be highly effective against COVID-19, severe disease and death. Here, we estimate vaccine effectiveness over time since the second dose of Comirnaty, Vaxzevria and Spikevax in England.
Methods
We used a test-negative case-control de...
We reviewed all genomic epidemiology studies on COVID-19 in long-term care facilities (LTCFs) that had been published to date. We found that staff and residents were usually infected with identical, or near identical, SARS-CoV-2 genomes. Outbreaks usually involved one predominant cluster, and the same lineages persisted in LTCFs despite infection c...
Background:
The B.1.617.2 (delta) variant of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (Covid-19), has contributed to a surge in cases in India and has now been detected across the globe, including a notable increase in cases in the United Kingdom. The effectiveness of the BNT1...
The COVID-19 pandemic has spread rapidly throughout the world. In the UK, the initial peak was in April 2020; in the county of Norfolk (UK) and surrounding areas, which has a stable, low-density population, over 3200 cases were reported between March and August 2020. As part of the activities of the national COVID-19 Genomics Consortium (COG-UK) we...
Background
Microbiological characterisation of co-infections and secondary infections in patients with COVID-19 is lacking, and antimicrobial use is high. We aimed to describe microbiologically confirmed co-infections and secondary infections, and antimicrobial use, in patients admitted to hospital with COVID-19.
Methods
The International Severe A...
Despite regional successes in controlling the SARS-CoV-2 pandemic, global cases have reached an all time high in April 2021 in part due to the evolution of more transmissible variants. Here we use the dense genomic surveillance generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 62 different lineages in each of 315 Engli...
Background:
The B.1.617.2 COVID-19 variant has contributed to the surge in cases in India and has now been detected across the globe, including a notable increase in cases in the UK. We estimate the effectiveness of the BNT162b2 and ChAdOx1 COVID-19 vaccines against this variant.
Methods:
A test negative case control design was used to estimate the...
Background:
The largest West African monkeypox outbreak began September 2017, in Nigeria. Four individuals traveling from Nigeria to the UK (2), Israel, and Singapore became the first human monkeypox cases exported from Africa, and a related nosocomial transmission event in the UK became the first confirmed human-to-human monkeypox transmission ev...
Diphtheria is a potentially life-threatening infection in humans. The three species capable of causing diphtheria are: Corynebacterium diphtheriae , C. ulcerans and C. pseudotuberculosis . Although UK cases are rare, recently there has been an increase in reported toxigenic C. ulceransassociated with companion animals. Potentially toxigenic coryneb...
In September 2018, monkeypox virus was transmitted from a patient to a healthcare worker in the United Kingdom. Transmission was probably through contact with contaminated bedding. Infection control precautions for contacts (vaccination, daily monitoring, staying home from work) were implemented. Of 134 potential contacts, 4 became ill; all patient...
Mycobacterial infection-related morbidity and mortality in patients following cardiopulmonary bypass surgery is high and and there is a growing need for a consensus-based expert opinion to provide international guidance for diagnosing, preventing and treating in these patients. In this document the International Society for Cardiovascular Infectiou...
Background
Changes over the last 5 years (2013–18) in the serotypes implicated in adult pneumococcal pneumonia and the patient groups associated with vaccine-type disease are largely unknown.
Methods
We conducted a population-based prospective cohort study of adults admitted to two large university hospitals with community-acquired pneumonia (CAP)...
Monkeypox outbreak in Blackpool, UK, 2018
In early 2017, a United Kingdom (UK)-born person in their 20s presented with a skin ulcer on the foot 3 weeks after returning from Ghana. The patient had last received a diphtheria-containing vaccine in 2013, completing the recommended course. MALDI-TOF of a cutaneous swab identified Corynebacterium diphtheriae. Real-time PCR ascertained the specie...
In early September 2018, two cases of monkeypox were reported in the United Kingdom (UK), diagnosed on 7 September in Cornwall (South West England) and 11 September in Blackpool (North West England). The cases were epidemiologically unconnected and had recently travelled to the UK from Nigeria, where monkeypox is currently circulating. We describe...
Background
Aqueous zanamivir solution, an investigational product, was provided by the manufacturer on compassionate grounds for parenteral administration to severe H1N1pdm09 influenza cases during the 2009 pandemic.
Objective
To describe characteristics and outcomes of United Kingdom patients receiving parenteral zanamivir therapy.
Methods
Colla...
Objectives:
Mycobacterium chimaera infection following cardiac surgery, due to contaminated cardiopulmonary bypass heater-cooler units, has been reported worldwide. However, the spectrum of clinical disease remains poorly understood. To address this, we report the clinical and laboratory features, treatment and outcome of the first 30 UK cases.
M...
Objectives:
To determine if there is a correlation between falling tonsillectomy numbers and increasing numbers of tonsillitis admissions and invasive Group A β-haemolytic streptococcus (iGAS) infection in children aged 14 and under in England.
Design:
An observational cross-sectional study was performed.
Setting:
The data extracted covered th...
Background:
The clinical manifestations of Group A streptococcus (GAS) - (Streptococcus pyogenes) are diverse, ranging from asymptomatic colonisation to devastating invasive disease. Maternity related clusters of invasive Group A streptococcus (iGAS) infection are complex to investigate and control, especially if recurrent.
Aim:
We report on the...
Background:
After decades of decreasing scarlet fever incidence, a dramatic increase was seen in England beginning in 2014. Investigations were launched to assess clinical and epidemiological patterns and identify potential causes.
Methods:
In this population-based surveillance study, we analysed statutory scarlet fever notifications held by Pub...
Summary
Background
Since 2013, over 100 cases of Mycobacterium chimaera prosthetic valve endocarditis and disseminated disease were notified in Europe and the USA, linked to contaminated heater–cooler units (HCUs) used during cardiac surgery. We did a molecular epidemiological investigation to establish the source of these patients' disease.
Metho...
The West African Ebola virus disease (EVD) epidemic was the largest and most devastating outbreak of EVD the world has ever seen. Its impact was felt far from the shores of Guinea, Liberia and Sierra Leone, with public health systems and clinicians across the globe confronted with an international response both in the affected region and within the...
The role of heater cooler units (HCUs) in the transmission of Mycobacterium chimaera during open heart surgery has been recognised since 2013. Subsequent investigations uncovered a remarkable global outbreak reflecting the wide distribution of implicated devices. HCUs are an essential component of cardiopulmonary bypass operations and their withdra...
Background
During a substantial elevation in scarlet fever (SF) notifications in 2014 a national genomic study was undertaken of Streptococcus pyogenes (Group A Streptococci, GAS) isolates from patients with SF with comparison to isolates from patients with invasive disease (iGAS) to test the hypotheses that the increase in SF was due to either the...
Background:
An urgent UK investigation was launched to assess risk of invasive Mycobacterium chimaera infection in cardiothoracic surgery and a possible association with cardiopulmonary bypass heater-cooler units following alerts in Switzerland and the Netherlands.
Methods:
Parallel investigations were pursued: i) identification of cardiopulmona...
Public Health England conducts enhanced national surveillance of tetanus, a potentially life-threatening vaccine-preventable disease. A standardized questionnaire was used to ascertain clinical and demographic details of individuals reported with clinically suspected tetanus. The 96 cases identified between 2001 and 2014 were analysed. The average...
Introduction:
Respiratory and cutaneous infection caused by toxigenic Corynebacterium spp. C. diphtheriae, C. ulcerans, and C. Pseudotuberculosis is a rare notifiable disease in the UK. In recent years the number of toxigenic C. ulcerans cases reported in the UK has been increasing. We describe the public health investigation and interventions fol...
The largest outbreak of Ebola virus disease (EVD) is ongoing in West Africa. Air-travel data indicate that outside Africa, the UK is among the countries at greatest risk of importing a case of EVD. Hospitals in England were therefore instructed to prepare for the assessment and early management of suspected cases. However, the response of hospitals...
Increases in scarlet fever above usual seasonal levels are currently being seen across the United Kingdom. Medical practitioners have been alerted to the exceptional increase in incidence. Given the potential for this to signal a population increase in invasive group A streptococcal disease, close monitoring of invasive disease is essential.
Background:
Febrile illness in returned travellers can rarely be diagnosed on clinical grounds alone. Poor integration and lack of awareness of diagnostic services delays diagnosis, with clinical and public health consequences. The Imported Fever Service (IFS) was established in 2012 as a UK-wide specialist diagnostic and clinical advice service...