Hester Allen’s research while affiliated with University of Oxford and other places

Introduction Electronic health records can be used to understand the diverse presentation of post-acute and long-term health outcomes following COVID-19 infection. In England, the UK Health Security Agency, in collaboration with the University of Oxford, has created the Evaluation of post-acute COVID-19 Health Outcomes (ECHOES) dataset to monitor how an initial SARS-CoV-2 infection episode is associated with changes in the risk of health outcomes that are recorded in routinely collected health data. Methods The ECHOES dataset is a national-level dataset combining national-level surveillance, administrative, and healthcare data. Entity resolution and data linkage methods are used to create a cohort of individuals who have tested positive and negative for SARS-CoV-2 in England throughout the COVID-19 pandemic, alongside information on a range of health outcomes, including diagnosed clinical conditions, mortality, and risk factor information. Results The dataset contains comprehensive COVID-19 testing data and demographic, socio-economic, and health-related information for 44 million individuals who tested for SARS-CoV-2 between March 2020 and April 2022, representing 15,720,286 individuals who tested positive and 42,351,016 individuals who tested negative. Discussion With the application of epidemiological and statistical methods, this dataset allows a range of clinical outcomes to be investigated, including pre-specified health conditions and mortality. Furthermore, understanding potential determinants of health outcomes can be gained, including pre-existing health conditions, acute disease characteristics, SARS-CoV-2 vaccination status, and genomic variants.

Introduction COVID-19 disease has been associated with severe illness, hospitalisation and death, however, widespread vaccination coverage in England has resulted in reduced disease severity. From 2022, the national vaccination programme has been run twice per year, prioritising older age groups or those classified as clinically vulnerable. Here we assess the trends in COVID-19 outcomes between September 2023 and April 2024, using national-level data held by the UK Health Security Agency (UKHSA). Methods Data linkage of national-level COVID-19 episode data, NHS emergency and hospital attendance data, and death registrations were used to analyse COVID-19 outcomes. Outcomes were defined as COVID-19 associated A&E attendances, hospital admissions, severe hospitalisations, and deaths The number and rate of each COVID-19 outcome category between September 2023 and April 2024 was calculated, stratified by clinical risk status and age and sex. Results The most common COVID-19 outcomes during this time-period were A&E attendance and hospital admission, with the rates highest among those aged 75 and over. Among this age group, all outcomes disproportionately affect those who have been identified as at clinical risk and those who were immunosuppressed. High rates of A&E attendance and hospital admission were also observed among infants (under 6 months old) but were lower for more severe outcomes. Discussion Groups that were most affected by COVID-19 outcomes were currently prioritised for COVID-19 vaccination in England, which will help protect against more severe outcomes including admission to intensive care and death. Routine national levels surveillance of COVID-19 outcomes is essential to monitor populations most of severe disease and informing vaccination policy.

Introduction Electronic health records can be used to understand the diverse presentation of post-acute and long-term health outcomes following COVID-19 infection. In England, the UK Health Security Agency in collaboration with the University of Oxford have created the ECHOES dataset to monitor how an initial SARS-CoV-2 infection episode is associated with changes in the risk of health outcomes that are recorded in routinely collected health data. Methods The ECHOES dataset is as a national level dataset combining national level surveillance, administrative, and healthcare data. Entity resolution and data linkages methods are used to create a cohort of individuals who have tested positive and negative for SARS-CoV-2 in England throughout the COVID-19 pandemic, alongside information on a range of health outcomes including diagnosed clinical conditions and mortality, and risk factor information. Results The dataset contains comprehensive COVID-19 testing data and demographic, socio economic and health related information for 44 million individuals, who tested for SARS-CoV-2 between March 2020 and April 2022, representing 15,720,286 individuals who tested positive and 42,351,016 individuals who tested negative. Discussion With the application of epidemiological and statistical methods, this dataset allows a range of clinical outcomes to be investigated, including pre-specified health conditions and mortality. Furthermore, understanding of potential determinants of health outcomes can be gained, including pre-existing health conditions, acute disease characteristics, SARS-CoV-2 vaccination status and genomic variant.

Objectives Although hepatitis A virus (HAV) and hepatitis B virus (HBV) immunisation is recommended in the UK for gay, bisexual and other men who have sex with men (GBMSM), data on immunisation coverage are limited. We aimed to determine the seroprevalence of HAV and HBV immunity among a sample of GBMSM attending sexual health services (SHS) in England. Methods Residual serum samples from HIV/syphilis testing for adult GBMSM attending eight SHS in London and one in Leeds were tested for markers of HAV immunity (HAV IgG) and HBV immunity (anti-HBs) using an unlinked anonymous approach. We estimated seroprevalence of HAV and HBV immunity overall and stratified by individuals’ characteristics, which we obtained from the Genitourinary Medicine Clinic Activity Dataset Sexually Transmitted Infection (STI) Surveillance System. We used logistic regression to calculate crude and adjusted ORs between seropositivity and demographic and clinical characteristics. Results Seroprevalence of immunity to HAV (74.5% of 2577) and HBV (77.1% of 2551) was high. In adjusted analysis, HAV IgG seroprevalence varied by clinic and WHO region of birth (global p<0.001 for each), increased with older age (ORs of 1.50 (95% CI 1.18 to 1.86), 2.91 (2.17 to 3.90) and 3.40 (2.44 to 4.75) for ages 26–35, 36–45 and >46 vs 18–25 years (global p<0.001), was higher in those with an STI in the past year (1.58 (1.25 to 2.00); p<0.001) and those who were living with HIV (1.82 (1.25 to 2.64); p<0.001). Anti-HBs seroprevalence varied by clinic (global p<0.001), increased with older age (global p<0.001) and was higher in those with an STI in the past year (1.61 (1.27 to 2.05); p<0.001). Conclusion Our findings provide a baseline seroprevalence from which to monitor serial levels of immunity to HBV and HAV in GBMSM accessing SHS. Levels of immunity for both viruses are high, noting samples were taken after recent widespread outbreaks and vaccination campaigns. High vaccine coverage in all GBMSM should be maintained to prevent further outbreaks.

Objectives Risk of death after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has fallen during the pandemic, largely due to immunity from vaccination. In England, the timing and extent of this reduction varied due to staggered eligibility during the primary vaccination campaign, based on age and clinical risk group. Duration of protection is less well understood. Our objective was to estimate the case fatality risk (CFR) by vaccination status and time since last dose during a period of widespread community testing, to better understand the impact of coronavirus disease 2019 (COVID-19) vaccination and duration of protection. Design SARS-CoV-2 cases diagnosed between May 2020 and February 2022 were linked to vaccine records from the National Immunisation Management System. CFR was calculated as the proportion of cases that died of COVID-19 per the death certificate, aggregated by week of specimen and stratified by 10-year age band and vaccination status. Setting England, UK. Participants A total of 10,616,148 SARS-CoV-2 cases, aged ≥18 years, recorded by England’s laboratory reporting system. Main outcome measures Case fatality risk of COVID-19, stratified by age band and vaccination status. Results Overall, a reduction in CFR was observed for all age bands, with a clear temporal link to when the age group became eligible for primary vaccination and then the first booster. CFR increased with age (0.3% 50–59 years; 1.2% 60–69; 4.7% 70–79; 16.3% 80+) and was highest in the unvaccinated – albeit a reduction was observed over time. The highest CFR was seen in the unvaccinated 80+ group prior to vaccination rollout (30.6%). CFR was consistently lowest in vaccinated populations within 6 months of last dose, yet increased after over 6 months elapsed since last dose, across all age bands. Conclusions COVID-19 CFR reduced after vaccination, with the lowest CFR seen across all age bands when vaccinated up to 6 months prior to specimen date. This provides some evidence for continued booster doses in older age groups.

Background Men and gender-diverse people who have sex with men are disproportionately affected by health conditions associated with increased risk of severe illness due to COVID-19 infection. Methods An online cross-sectional survey of men and gender-diverse people who have sex with men in the UK recruited via social networking and dating applications from 22 November-12 December 2021. Eligible participants included self-identifying men, transgender women, or gender-diverse individuals assigned male at birth (AMAB), aged ≥ 16, who were UK residents, and self-reported having had sex with an individual AMAB in the last year. We calculated self-reported COVID-19 test-positivity, proportion reporting long COVID, and COVID-19 vaccination uptake anytime from pandemic start to survey completion (November/December 2021). Logistic regression was used to assess sociodemographic, clinical, and behavioural characteristics associated with SARS-CoV-2 (COVID-19) test positivity and complete vaccination (≥ 2 vaccine doses). Results Among 1,039 participants (88.1% white, median age 41 years [interquartile range: 31-51]), 18.6% (95% CI: 16.3%-21.1%) reported COVID-19 test positivity, 8.3% (95% CI: 6.7%-10.1%) long COVID, and 94.5% (95% CI: 93.3%-96.1%) complete COVID-19 vaccination through late 2021. In multivariable models, COVID-19 test positivity was associated with UK country of residence (aOR: 2.22 [95% CI: 1.26-3.92], England vs outside England) and employment (aOR: 1.55 [95% CI: 1.01-2.38], current employment vs not employed). Complete COVID-19 vaccination was associated with age (aOR: 1.04 [95% CI: 1.01-1.06], per increasing year), gender (aOR: 0.26 [95% CI: 0.09-0.72], gender minority vs cisgender), education (aOR: 2.11 [95% CI: 1.12-3.98], degree-level or higher vs below degree-level), employment (aOR: 2.07 [95% CI: 1.08-3.94], current employment vs not employed), relationship status (aOR: 0.50 [95% CI: 0.25-1.00], single vs in a relationship), COVID-19 infection history (aOR: 0.47 [95% CI: 0.25-0.88], test positivity or self-perceived infection vs no history), known HPV vaccination (aOR: 3.32 [95% CI: 1.43-7.75]), and low self-worth (aOR: 0.29 [95% CI: 0.15-0.54]). Conclusions In this community sample, COVID-19 vaccine uptake was high overall, though lower among younger age-groups, gender minorities, and those with poorer well-being. Efforts are needed to limit COVID-19 related exacerbation of health inequalities in groups who already experience a greater burden of poor health relative to other men who have sex with men.

Background The World Health Organization recommends changing the first-line antimicrobial treatment for gonorrhoea when ≥ 5% of Neisseria gonorrhoeae cases fail treatment or are resistant. Susceptibility to ceftriaxone, the last remaining treatment option has been decreasing in many countries. We used antimicrobial resistance surveillance data and developed mathematical models to project the time to reach the 5% threshold for resistance to first-line antimicrobials used for N. gonorrhoeae. Methods We used data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) in England and Wales from 2000–2018 about minimum inhibitory concentrations (MIC) for ciprofloxacin, azithromycin, cefixime and ceftriaxone and antimicrobial treatment in two groups, heterosexual men and women (HMW) and men who have sex with men (MSM). We developed two susceptible-infected-susceptible models to fit these data and produce projections of the proportion of resistance until 2030. The single-step model represents the situation in which a single mutation results in antimicrobial resistance. In the multi-step model, the sequential accumulation of resistance mutations is reflected by changes in the MIC distribution. Results The single-step model described resistance to ciprofloxacin well. Both single-step and multi-step models could describe azithromycin and cefixime resistance, with projected resistance levels higher with the multi-step than the single step model. For ceftriaxone, with very few observed cases of full resistance, the multi-step model was needed to describe long-term dynamics of resistance. Extrapolating from the observed upward drift in MIC values, the multi-step model projected ≥ 5% resistance to ceftriaxone could be reached by 2030, based on treatment pressure alone. Ceftriaxone resistance was projected to rise to 13.2% (95% credible interval [CrI]: 0.7–44.8%) among HMW and 19.6% (95%CrI: 2.6–54.4%) among MSM by 2030. Conclusions New first-line antimicrobials for gonorrhoea treatment are needed. In the meantime, public health authorities should strengthen surveillance for AMR in N. gonorrhoeae and implement strategies for continued antimicrobial stewardship. Our models show the utility of long-term representative surveillance of gonococcal antimicrobial susceptibility data and can be adapted for use in, and for comparison with, other countries.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) rapidly replaced Delta (B.1.617.2) to become dominant in England. Our study assessed differences in transmission between Omicron and Delta using two independent data sources and methods. Omicron and Delta cases were identified through genomic sequencing, genotyping and S-gene target failure in England from 5–11 December 2021. Secondary attack rates for named contacts were calculated in household and non-household settings using contact tracing data, while household clustering was identified using national surveillance data. Logistic regression models were applied to control for factors associated with transmission for both methods. For contact tracing data, higher secondary attack rates for Omicron vs. Delta were identified in households (15.0% vs. 10.8%) and non-households (8.2% vs. 3.7%). For both variants, in household settings, onward transmission was reduced from cases and named contacts who had three doses of vaccine compared to two, but this effect was less pronounced for Omicron (adjusted risk ratio, aRR 0.78 and 0.88) than Delta (aRR 0.62 and 0.68). In non-household settings, a similar reduction was observed only in contacts who had three doses vs. two doses for both Delta (aRR 0.51) and Omicron (aRR 0.76). For national surveillance data, the risk of household clustering, was increased 3.5-fold for Omicron compared to Delta (aRR 3.54 (3.29–3.81)). Our study identified increased risk of onward transmission of Omicron, consistent with its successful global displacement of Delta. We identified a reduced effectiveness of vaccination in lowering risk of transmission, a likely contributor for the rapid propagation of Omicron.