COVID-19 inequalities in England: a mathematical modelling study of transmission risk and clinical vulnerability by socioeconomic status.

BACKGROUND: The COVID-19 pandemic resulted in major inequalities in infection and disease burden between areas of varying socioeconomic deprivation in many countries, including England. Areas of higher deprivation tend to have a different population structure-generally younger-which can increase viral transmission due to higher contact rates in school-going children and working-age adults. Higher deprivation is also associated with a higher presence of chronic comorbidities, which were convincingly demonstrated to be risk factors for severe COVID-19 disease. These two major factors need to be combined to better understand and quantify their relative importance in the observed COVID-19 inequalities. METHODS: We used UK Census data on health status and demography stratified by decile of the Index of Multiple Deprivation (IMD), which is a measure of socioeconomic deprivation. We calculated epidemiological impact using an age-stratified COVID-19 transmission model, which incorporated different contact patterns and clinical health profiles by decile. To separate the contribution of each factor, we considered a scenario where the clinical health profile of all deciles was at the level of the least deprived. We also considered the effectiveness of school closures and vaccination of over 65-year-olds in each decile. RESULTS: In the modelled epidemics in urban areas, the most deprived decile experienced 9% more infections, 13% more clinical cases, and a 97% larger peak clinical size than the least deprived; we found similar inequalities in rural areas. Twenty-one per cent of clinical cases and 16% of deaths in England observed under the model assumptions would not occur if all deciles experienced the clinical health profile of the least deprived decile. We found that more deaths were prevented in more affluent areas during school closures and vaccination rollouts. CONCLUSIONS: This study demonstrates that both clinical and demographic factors synergise to generate health inequalities in COVID-19, that improving the clinical health profile of populations would increase health equity, and that some interventions can increase health inequalities.

Healthcare utilisation in people with long COVID: an OpenSAFELY cohort study.

BACKGROUND: Long COVID potentially increases healthcare utilisation and costs. However, its impact on the NHS remains to be determined. METHODS: This study aims to assess the healthcare utilisation of individuals with long COVID. With the approval of NHS England, we conducted a matched cohort study using primary and secondary care data via OpenSAFELY, a platform for analysing anonymous electronic health records. The long COVID exposure group, defined by diagnostic codes, was matched with five comparators without long COVID between Nov 2020 and Jan 2023. We compared their total healthcare utilisation from GP consultations, prescriptions, hospital admissions, A&E visits, and outpatient appointments. Healthcare utilisation and costs were evaluated using a two-part model adjusting for covariates. Using a difference-in-difference model, we also compared healthcare utilisation after long COVID with pre-pandemic records. RESULTS: We identified 52,988 individuals with a long COVID diagnosis, matched to 264,867 comparators without a diagnosis. In the 12 months post-diagnosis, there was strong evidence that those with long COVID were more likely to use healthcare resources (OR: 8.29, 95% CI: 7.74-8.87), and have 49% more healthcare utilisation (RR: 1.49, 95% CI: 1.48-1.51). Our model estimated that the long COVID group had 30 healthcare visits per year (predicted mean: 29.23, 95% CI: 28.58-29.92), compared to 16 in the comparator group (predicted mean visits: 16.04, 95% CI: 15.73-16.36). Individuals with long COVID were more likely to have non-zero healthcare expenditures (OR = 7.66, 95% CI = 7.20-8.15), with costs being 44% higher than the comparator group (cost ratio = 1.44, 95% CI: 1.39-1.50). The long COVID group costs approximately £2500 per person per year (predicted mean cost: £2562.50, 95% CI: £2335.60-£2819.22), and the comparator group costs £1500 (predicted mean cost: £1527.43, 95% CI: £1404.33-1664.45). Historically, individuals with long COVID utilised healthcare resources more frequently, but their average healthcare utilisation increased more after being diagnosed with long COVID, compared to the comparator group. CONCLUSIONS: Long COVID increases healthcare utilisation and costs. Public health policies should allocate more resources towards preventing, treating, and supporting individuals with long COVID.

Call detail record aggregation methodology impacts infectious disease models informed by human mobility.

This paper demonstrates how two different methods used to calculate population-level mobility from Call Detail Records (CDR) produce varying predictions of the spread of epidemics informed by these data. Our findings are based on one CDR dataset describing inter-district movement in Ghana in 2021, produced using two different aggregation methodologies. One methodology, "all pairs," is designed to retain long distance network connections while the other, "sequential" methodology is designed to accurately reflect the volume of travel between locations. We show how the choice of methodology feeds through models of human mobility to the predictions of a metapopulation SEIR model of disease transmission. We also show that this impact varies depending on the location of pathogen introduction and the transmissibility of infections. For central locations or highly transmissible diseases, we do not observe significant differences between aggregation methodologies on the predicted spread of disease. For less transmissible diseases or those introduced into remote locations, we find that the choice of aggregation methodology influences the speed of spatial spread as well as the size of the peak number of infections in individual districts. Our findings can help researchers and users of epidemiological models to understand how methodological choices at the level of model inputs may influence the results of models of infectious disease transmission, as well as the circumstances in which these choices do not alter model predictions.

How immunity from and interaction with seasonal coronaviruses can shape SARS-CoV-2 epidemiology.

We hypothesized that cross-protection from seasonal epidemics of human coronaviruses (HCoVs) could have affected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, including generating reduced susceptibility in children. To determine what the prepandemic distribution of immunity to HCoVs was, we fitted a mathematical model to 6 y of seasonal coronavirus surveillance data from England and Wales. We estimated a duration of immunity to seasonal HCoVs of 7.8 y (95% CI 6.3 to 8.1) and show that, while cross-protection between HCoV and SARS-CoV-2 may contribute to the age distribution, it is insufficient to explain the age pattern of SARS-CoV-2 infections in the first wave of the pandemic in England and Wales. Projections from our model illustrate how different strengths of cross-protection between circulating coronaviruses could determine the frequency and magnitude of SARS-CoV-2 epidemics over the coming decade, as well as the potential impact of cross-protection on future seasonal coronavirus transmission.

Correspondence to: Estimating the full health and economic benefits of current and future influenza vaccines.

We recently published an article in BMC Medicine looking at the potential health and economic impact of paediatric vaccination using next-generation influenza vaccines in Kenya: a modelling study. In their commentary on our article, Lafond et al. highlight the potential importance of the wider benefits of vaccination on cost-effectiveness. Whilst we agree with many points raised in the commentary, we think it raises further interesting discussion points, specifically around model complexity, model assumptions and data availability. These points are both relevant to this manuscript but have wider implications for vaccine cost-effectiveness studies.

Potential health and economic impact of paediatric vaccination using next-generation influenza vaccines in Kenya: a modelling study.

BACKGROUND: Influenza is a major year-round cause of respiratory illness in Kenya, particularly in children under 5. Current influenza vaccines result in short-term, strain-specific immunity and were found in a previous study not to be cost-effective in Kenya. However, next-generation vaccines are in development that may have a greater impact and cost-effectiveness profile. METHODS: We expanded a model previously used to evaluate the cost-effectiveness of seasonal influenza vaccines in Kenya to include next-generation vaccines by allowing for enhanced vaccine characteristics and multi-annual immunity. We specifically examined vaccinating children under 5 years of age with improved vaccines, evaluating vaccines with combinations of increased vaccine effectiveness, cross-protection between strains (breadth) and duration of immunity. We evaluated cost-effectiveness using incremental cost-effectiveness ratios (ICERs) and incremental net monetary benefits (INMBs) for a range of values for the willingness-to-pay (WTP) per DALY averted. Finally, we estimated threshold per-dose vaccine prices at which vaccination becomes cost-effective. RESULTS: Next-generation vaccines can be cost-effective, dependent on the vaccine characteristics and assumed WTP thresholds. Universal vaccines (assumed to provide long-term and broad immunity) are most cost-effective in Kenya across three of four WTP thresholds evaluated, with the lowest median value of ICER per DALY averted ($263, 95% Credible Interval (CrI): $ - 1698, $1061) and the highest median INMBs. At a WTP of $623, universal vaccines are cost-effective at or below a median price of $5.16 per dose (95% CrI: $0.94, $18.57). We also show that the assumed mechanism underlying infection-derived immunity strongly impacts vaccine outcomes. CONCLUSIONS: This evaluation provides evidence for country-level decision makers about future next-generation vaccine introduction, as well as global research funders about the potential market for these vaccines. Next-generation vaccines may offer a cost-effective intervention to reduce influenza burden in low-income countries with year-round seasonality like Kenya.

Transient increased risk of influenza infection following RSV infection in South Africa: findings from the PHIRST study, South Africa, 2016-2018.

BACKGROUND: Large-scale prevention of respiratory syncytial virus (RSV) infection may have ecological consequences for co-circulating pathogens, including influenza. We assessed if and for how long RSV infection alters the risk for subsequent influenza infection. METHODS: We analysed a prospective longitudinal cohort study conducted in South Africa between 2016 and 2018. For participating households, nasopharyngeal samples were taken twice weekly, irrespective of symptoms, across three respiratory virus seasons, and real-time polymerase chain reaction (PCR) was used to identify infection with RSV and/or influenza. We fitted an individual-level hidden Markov transmission model in order to estimate RSV and influenza infection rates and their interdependence. RESULTS: Of a total of 122,113 samples collected, 1265 (1.0%) were positive for influenza and 1002 (0.8%) positive for RSV, with 15 (0.01%) samples from 12 individuals positive for both influenza and RSV. We observed a 2.25-fold higher incidence of co-infection than expected if assuming infections were unrelated. We estimated that infection with influenza is 2.13 (95% CI 0.97-4.69) times more likely when already infected with, and for a week following, RSV infection, adjusted for age. This equates to 1.4% of influenza infections that may be attributable to RSV in this population. Due to the local seasonality (RSV season precedes the influenza season), we were unable to estimate changes in RSV infection risk following influenza infection. CONCLUSIONS: We find no evidence to suggest that RSV was associated with a subsequent reduced risk of influenza infection. Instead, we observed an increased risk for influenza infection for a short period after infection. However, the impact on population-level transmission dynamics of this individual-level synergistic effect was not measurable in this setting.

Assessing the impacts of COVID-19 vaccination programme's timing and speed on health benefits, cost-effectiveness, and relative affordability in 27 African countries.

BACKGROUND: The COVID-19 vaccine supply shortage in 2021 constrained roll-out efforts in Africa while populations experienced waves of epidemics. As supply improves, a key question is whether vaccination remains an impactful and cost-effective strategy given changes in the timing of implementation. METHODS: We assessed the impact of vaccination programme timing using an epidemiological and economic model. We fitted an age-specific dynamic transmission model to reported COVID-19 deaths in 27 African countries to approximate existing immunity resulting from infection before substantial vaccine roll-out. We then projected health outcomes (from symptomatic cases to overall disability-adjusted life years (DALYs) averted) for different programme start dates (01 January to 01 December 2021, n = 12) and roll-out rates (slow, medium, fast; 275, 826, and 2066 doses/million population-day, respectively) for viral vector and mRNA vaccines by the end of 2022. Roll-out rates used were derived from observed uptake trajectories in this region. Vaccination programmes were assumed to prioritise those above 60 years before other adults. We collected data on vaccine delivery costs, calculated incremental cost-effectiveness ratios (ICERs) compared to no vaccine use, and compared these ICERs to GDP per capita. We additionally calculated a relative affordability measure of vaccination programmes to assess potential nonmarginal budget impacts. RESULTS: Vaccination programmes with early start dates yielded the most health benefits and lowest ICERs compared to those with late starts. While producing the most health benefits, fast vaccine roll-out did not always result in the lowest ICERs. The highest marginal effectiveness within vaccination programmes was found among older adults. High country income groups, high proportions of populations over 60 years or non-susceptible at the start of vaccination programmes are associated with low ICERs relative to GDP per capita. Most vaccination programmes with small ICERs relative to GDP per capita were also relatively affordable. CONCLUSION: Although ICERs increased significantly as vaccination programmes were delayed, programmes starting late in 2021 may still generate low ICERs and manageable affordability measures. Looking forward, lower vaccine purchasing costs and vaccines with improved efficacies can help increase the economic value of COVID-19 vaccination programmes.

The COVID-19 response illustrates that traditional academic reward structures and metrics do not reflect crucial contributions to modern science.

The COVID-19 pandemic has motivated many open and collaborative analytical research projects with real-world impact. However, despite their value, such activities are generally overlooked by traditional academic metrics. Science is ultimately improved by analytical work, whether ensuring reproducible and well-documented code to accompany papers, developing and maintaining flexible tools, sharing and curating data, or disseminating analysis to wider audiences. To increase the impact and sustainability of modern science, it will be crucial to ensure these analytical activities-and the people who do them-are valued in academia.

Evidence for influenza and RSV interaction from 10 years of enhanced surveillance in Nha Trang, Vietnam, a modelling study.

Influenza and Respiratory Syncytial Virus (RSV) interact within their host posing the concern for impacts on heterologous viruses following vaccination. We aimed to estimate the population level impact of their interaction. We developed a dynamic age-stratified two-pathogen mathematical model that includes pathogen interaction through competition for infection and enhanced severity of dual infections. We used parallel tempering to fit its parameters to 11 years of enhanced hospital-based surveillance for acute respiratory illnesses (ARI) in children under 5 years old in Nha Trang, Vietnam. The data supported either a 41% (95%CrI: 36-54) reduction in susceptibility following infection and for 10.0 days (95%CrI 7.1-12.8) thereafter, or no change in susceptibility following infection. We estimate that co-infection increased the probability for an infection in <2y old children to be reported 7.2 fold (95%CrI 5.0-11.4); or 16.6 fold (95%CrI 14.5-18.4) in the moderate or low interaction scenarios. Absence of either pathogen was not to the detriment of the other. We find stronger evidence for severity enhancing than for acquisition limiting interaction. In this setting vaccination against either pathogen is unlikely to have a major detrimental effect on the burden of disease caused by the other.

The Impact of Cocirculating Pathogens on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)/Coronavirus Disease 2019 Surveillance: How Concurrent Epidemics May Introduce Bias and Decrease the Observed SARS-CoV-2 Percentage Positivity.

BACKGROUND: Circulation of seasonal non-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) respiratory viruses with syndromic overlap during the coronavirus disease 2019 (COVID-19) pandemic may alter the quality of COVID-19 surveillance, with possible consequences for real-time analysis and delay in implementation of control measures. METHODS: Using a multipathogen susceptible-exposed-infectious-recovered (SEIR) transmission model formalizing cocirculation of SARS-CoV-2 and another respiratory virus, we assessed how an outbreak of secondary virus may affect 2 COVID-19 surveillance indicators: testing demand and positivity. Using simulation, we assessed to what extent the use of multiplex polymerase chain reaction tests on a subsample of symptomatic individuals can help correct the observed SARS-CoV-2 percentage positivity and improve surveillance quality. RESULTS: We find that a non-SARS-CoV-2 epidemic strongly increases SARS-CoV-2 daily testing demand and artificially reduces the observed SARS-CoV-2 percentage positivity for the duration of the outbreak. We estimate that performing 1 multiplex test for every 1000 COVID-19 tests on symptomatic individuals could be sufficient to maintain surveillance of other respiratory viruses in the population and correct the observed SARS-CoV-2 percentage positivity. CONCLUSIONS: This study showed that cocirculating respiratory viruses can distort SARS-CoV-2 surveillance. Correction of the positivity rate can be achieved by using multiplex polymerase chain reaction tests, and a low number of samples is sufficient to avoid bias in SARS-CoV-2 surveillance.

Long-Term Health-Related Quality of Life in Non-Hospitalized Coronavirus Disease 2019 (COVID-19) Cases With Confirmed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in England: Longitudinal Analysis and Cross-Sectional Comparison With Controls.

BACKGROUND: We aimed to quantify the unknown losses in health-related quality of life of coronavirus disease 2019 (COVID-19) cases using quality-adjusted lifedays (QALDs) and the recommended EQ-5D instrument in England. METHODS: Prospective cohort study of nonhospitalized, polymerase chain reaction (PCR)-confirmed severe acute respiratory syndrome coronavirus 2-positive (SARS-CoV-2-positive) cases aged 12-85 years and followed up for 6 months from 1 December 2020, with cross-sectional comparison to SARS-CoV-2-negative controls. Main outcomes were QALD losses; physical symptoms; and COVID-19-related private expenditures. We analyzed results using multivariable regressions with post hoc weighting by age and sex, and conditional logistic regressions for the association of each symptom and EQ-5D limitation on cases and controls. RESULTS: Of 548 cases (mean age 41.1 years; 61.5% female), 16.8% reported physical symptoms at month 6 (most frequently extreme tiredness, headache, loss of taste and/or smell, and shortness of breath). Cases reported more limitations with doing usual activities than controls. Almost half of cases spent a mean of £18.1 on nonprescription drugs (median: £10.0), and 52.7% missed work or school for a mean of 12 days (median: 10). On average, all cases lost 13.7 (95% confidence interval [CI]: 9.7, 17.7) QALDs, whereas those reporting symptoms at month 6 lost 32.9 (95% CI: 24.5, 37.6) QALDs. Losses also increased with older age. Cumulatively, the health loss from morbidity contributes at least 18% of the total COVID-19-related disease burden in the England. CONCLUSIONS: One in 6 cases report ongoing symptoms at 6 months, and 10% report prolonged loss of function compared to pre-COVID-19 baselines. A marked health burden was observed among older COVID-19 cases and those with persistent physical symptoms.

Severity of Severe Acute Respiratory System Coronavirus 2 (SARS-CoV-2) Alpha Variant (B.1.1.7) in England.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) alpha variant (B.1.1.7) is associated with higher transmissibility than wild-type virus, becoming the dominant variant in England by January 2021. We aimed to describe the severity of the alpha variant in terms of the pathway of disease from testing positive to hospital admission and death. METHODS: With the approval of NHS England, we linked individual-level data from primary care with SARS-CoV-2 community testing, hospital admission, and Office for National Statistics all-cause death data. We used testing data with S-gene target failure as a proxy for distinguishing alpha and wild-type cases, and stratified Cox proportional hazards regression to compare the relative severity of alpha cases with wild-type diagnosed from 16 November 2020 to 11 January 2021. RESULTS: Using data from 185 234 people who tested positive for SARS-CoV-2 in the community (alpha = 93 153; wild-type = 92 081), in fully adjusted analysis accounting for individual-level demographics and comorbidities as well as regional variation in infection incidence, we found alpha associated with 73% higher hazards of all-cause death (adjusted hazard ratio [aHR]: 1.73; 95% confidence interval [CI]: 1.41-2.13; P < .0001) and 62% higher hazards of hospital admission (1.62; 1.48-1.78; P < .0001) compared with wild-type virus. Among patients already admitted to the intensive care unit, the association between alpha and increased all-cause mortality was smaller and the CI included the null (aHR: 1.20; 95% CI: .74-1.95; P = .45). CONCLUSIONS: The SARS-CoV-2 alpha variant is associated with an increased risk of both hospitalization and mortality than wild-type virus.

Seroprevalence of SARS-Cov-2 Antibodies in Adults, Arkhangelsk, Russia.

Population-based data on coronavirus disease in Russia and on the immunogenicity of the Sputnik V vaccine are sparse. In a survey of 1,080 residents of Arkhangelsk 40-75 years of age, 65% were seropositive for IgG. Fifteen percent of participants had been vaccinated; of those, 97% were seropositive.

Correction: COVID-19 vaccination in Sindh Province, Pakistan: A modelling study of health impact and cost-effectiveness.

[This corrects the article DOI: 10.1371/journal.pmed.1003815.].

Overall and cause-specific hospitalisation and death after COVID-19 hospitalisation in England: A cohort study using linked primary care, secondary care, and death registration data in the OpenSAFELY platform.

BACKGROUND: There is concern about medium to long-term adverse outcomes following acute Coronavirus Disease 2019 (COVID-19), but little relevant evidence exists. We aimed to investigate whether risks of hospital admission and death, overall and by specific cause, are raised following discharge from a COVID-19 hospitalisation. METHODS AND FINDINGS: With the approval of NHS-England, we conducted a cohort study, using linked primary care and hospital data in OpenSAFELY to compare risks of hospital admission and death, overall and by specific cause, between people discharged from COVID-19 hospitalisation (February to December 2020) and surviving at least 1 week, and (i) demographically matched controls from the 2019 general population; and (ii) people discharged from influenza hospitalisation in 2017 to 2019. We used Cox regression adjusted for age, sex, ethnicity, obesity, smoking status, deprivation, and comorbidities considered potential risk factors for severe COVID-19 outcomes. We included 24,673 postdischarge COVID-19 patients, 123,362 general population controls, and 16,058 influenza controls, followed for ≤315 days. COVID-19 patients had median age of 66 years, 13,733 (56%) were male, and 19,061 (77%) were of white ethnicity. Overall risk of hospitalisation or death (30,968 events) was higher in the COVID-19 group than general population controls (fully adjusted hazard ratio [aHR] 2.22, 2.14 to 2.30, p < 0.001) but slightly lower than the influenza group (aHR 0.95, 0.91 to 0.98, p = 0.004). All-cause mortality (7,439 events) was highest in the COVID-19 group (aHR 4.82, 4.48 to 5.19 versus general population controls [p < 0.001] and 1.74, 1.61 to 1.88 versus influenza controls [p < 0.001]). Risks for cause-specific outcomes were higher in COVID-19 survivors than in general population controls and largely similar or lower in COVID-19 compared with influenza patients. However, COVID-19 patients were more likely than influenza patients to be readmitted or die due to their initial infection or other lower respiratory tract infection (aHR 1.37, 1.22 to 1.54, p < 0.001) and to experience mental health or cognitive-related admission or death (aHR 1.37, 1.02 to 1.84, p = 0.039); in particular, COVID-19 survivors with preexisting dementia had higher risk of dementia hospitalisation or death (age- and sex-adjusted HR 2.47, 1.37 to 4.44, p = 0.002). Limitations of our study were that reasons for hospitalisation or death may have been misclassified in some cases due to inconsistent use of codes, and we did not have data to distinguish COVID-19 variants. CONCLUSIONS: In this study, we observed that people discharged from a COVID-19 hospital admission had markedly higher risks for rehospitalisation and death than the general population, suggesting a substantial extra burden on healthcare. Most risks were similar to those observed after influenza hospitalisations, but COVID-19 patients had higher risks of all-cause mortality, readmission or death due to the initial infection, and dementia death, highlighting the importance of postdischarge monitoring.

Ethnic differences in SARS-CoV-2 infection and COVID-19-related hospitalisation, intensive care unit admission, and death in 17 million adults in England: an observational cohort study using the OpenSAFELY platform.

BACKGROUND: COVID-19 has disproportionately affected minority ethnic populations in the UK. Our aim was to quantify ethnic differences in SARS-CoV-2 infection and COVID-19 outcomes during the first and second waves of the COVID-19 pandemic in England. METHODS: We conducted an observational cohort study of adults (aged ≥18 years) registered with primary care practices in England for whom electronic health records were available through the OpenSAFELY platform, and who had at least 1 year of continuous registration at the start of each study period (Feb 1 to Aug 3, 2020 [wave 1], and Sept 1 to Dec 31, 2020 [wave 2]). Individual-level primary care data were linked to data from other sources on the outcomes of interest: SARS-CoV-2 testing and positive test results and COVID-19-related hospital admissions, intensive care unit (ICU) admissions, and death. The exposure was self-reported ethnicity as captured on the primary care record, grouped into five high-level census categories (White, South Asian, Black, other, and mixed) and 16 subcategories across these five categories, as well as an unknown ethnicity category. We used multivariable Cox regression to examine ethnic differences in the outcomes of interest. Models were adjusted for age, sex, deprivation, clinical factors and comorbidities, and household size, with stratification by geographical region. FINDINGS: Of 17 288 532 adults included in the study (excluding care home residents), 10 877 978 (62·9%) were White, 1 025 319 (5·9%) were South Asian, 340 912 (2·0%) were Black, 170 484 (1·0%) were of mixed ethnicity, 320 788 (1·9%) were of other ethnicity, and 4 553 051 (26·3%) were of unknown ethnicity. In wave 1, the likelihood of being tested for SARS-CoV-2 infection was slightly higher in the South Asian group (adjusted hazard ratio 1·08 [95% CI 1·07-1·09]), Black group (1·08 [1·06-1·09]), and mixed ethnicity group (1·04 [1·02-1·05]) and was decreased in the other ethnicity group (0·77 [0·76-0·78]) relative to the White group. The risk of testing positive for SARS-CoV-2 infection was higher in the South Asian group (1·99 [1·94-2·04]), Black group (1·69 [1·62-1·77]), mixed ethnicity group (1·49 [1·39-1·59]), and other ethnicity group (1·20 [1·14-1·28]). Compared with the White group, the four remaining high-level ethnic groups had an increased risk of COVID-19-related hospitalisation (South Asian group 1·48 [1·41-1·55], Black group 1·78 [1·67-1·90], mixed ethnicity group 1·63 [1·45-1·83], other ethnicity group 1·54 [1·41-1·69]), COVID-19-related ICU admission (2·18 [1·92-2·48], 3·12 [2·65-3·67], 2·96 [2·26-3·87], 3·18 [2·58-3·93]), and death (1·26 [1·15-1·37], 1·51 [1·31-1·71], 1·41 [1·11-1·81], 1·22 [1·00-1·48]). In wave 2, the risks of hospitalisation, ICU admission, and death relative to the White group were increased in the South Asian group but attenuated for the Black group compared with these risks in wave 1. Disaggregation into 16 ethnicity groups showed important heterogeneity within the five broader categories. INTERPRETATION: Some minority ethnic populations in England have excess risks of testing positive for SARS-CoV-2 and of adverse COVID-19 outcomes compared with the White population, even after accounting for differences in sociodemographic, clinical, and household characteristics. Causes are likely to be multifactorial, and delineating the exact mechanisms is crucial. Tackling ethnic inequalities will require action across many fronts, including reducing structural inequalities, addressing barriers to equitable care, and improving uptake of testing and vaccination. FUNDING: Medical Research Council.

Projecting contact matrices in 177 geographical regions: An update and comparison with empirical data for the COVID-19 era.

Mathematical models have played a key role in understanding the spread of directly-transmissible infectious diseases such as Coronavirus Disease 2019 (COVID-19), as well as the effectiveness of public health responses. As the risk of contracting directly-transmitted infections depends on who interacts with whom, mathematical models often use contact matrices to characterise the spread of infectious pathogens. These contact matrices are usually generated from diary-based contact surveys. However, the majority of places in the world do not have representative empirical contact studies, so synthetic contact matrices have been constructed using more widely available setting-specific survey data on household, school, classroom, and workplace composition combined with empirical data on contact patterns in Europe. In 2017, the largest set of synthetic contact matrices to date were published for 152 geographical locations. In this study, we update these matrices with the most recent data and extend our analysis to 177 geographical locations. Due to the observed geographic differences within countries, we also quantify contact patterns in rural and urban settings where data is available. Further, we compare both the 2017 and 2020 synthetic matrices to out-of-sample empirically-constructed contact matrices, and explore the effects of using both the empirical and synthetic contact matrices when modelling physical distancing interventions for the COVID-19 pandemic. We found that the synthetic contact matrices show qualitative similarities to the contact patterns in the empirically-constructed contact matrices. Models parameterised with the empirical and synthetic matrices generated similar findings with few differences observed in age groups where the empirical matrices have missing or aggregated age groups. This finding means that synthetic contact matrices may be used in modelling outbreaks in settings for which empirical studies have yet to be conducted.

Detecting behavioural changes in human movement to inform the spatial scale of interventions against COVID-19.

On March 23 2020, the UK enacted an intensive, nationwide lockdown to mitigate transmission of COVID-19. As restrictions began to ease, more localized interventions were used to target resurgences in transmission. Understanding the spatial scale of networks of human interaction, and how these networks change over time, is critical to targeting interventions at the most at-risk areas without unnecessarily restricting areas at low risk of resurgence. We use detailed human mobility data aggregated from Facebook users to determine how the spatially-explicit network of movements changed before and during the lockdown period, in response to the easing of restrictions, and to the introduction of locally-targeted interventions. We also apply community detection techniques to the weighted, directed network of movements to identify geographically-explicit movement communities and measure the evolution of these community structures through time. We found that the mobility network became more sparse and the number of mobility communities decreased under the national lockdown, a change that disproportionately affected long distance connections central to the mobility network. We also found that the community structure of areas in which locally-targeted interventions were implemented following epidemic resurgence did not show reorganization of community structure but did show small decreases in indicators of travel outside of local areas. We propose that communities detected using Facebook or other mobility data be used to assess the impact of spatially-targeted restrictions and may inform policymakers about the spatial extent of human movement patterns in the UK. These data are available in near real-time, allowing quantification of changes in the distribution of the population across the UK, as well as changes in travel patterns to inform our understanding of the impact of geographically-targeted interventions.

Recording of 'COVID-19 vaccine declined': a cohort study on 57.9 million National Health Service patients' records in situ using OpenSAFELY, England, 8 December 2020 to 25 May 2021.

BackgroundPriority patients in England were offered COVID-19 vaccination by mid-April 2021. Codes in clinical record systems can denote the vaccine being declined.AimWe describe records of COVID-19 vaccines being declined, according to clinical and demographic factors.MethodsWith the approval of NHS England, we conducted a retrospective cohort study between 8 December 2020 and 25 May 2021 with primary care records for 57.9 million patients using OpenSAFELY, a secure health analytics platform. COVID-19 vaccination priority patients were those aged ≥ 50 years or ≥ 16 years clinically extremely vulnerable (CEV) or 'at risk'. We describe the proportion recorded as declining vaccination for each group and stratified by clinical and demographic subgroups, subsequent vaccination and distribution of clinical code usage across general practices.ResultsOf 24.5 million priority patients, 663,033 (2.7%) had a decline recorded, while 2,155,076 (8.8%) had neither a vaccine nor decline recorded. Those recorded as declining, who were subsequently vaccinated (n = 125,587; 18.9%) were overrepresented in the South Asian population (32.3% vs 22.8% for other ethnicities aged ≥ 65 years). The proportion of declining unvaccinated patients was highest in CEV (3.3%), varied strongly with ethnicity (black 15.3%, South Asian 5.6%, white 1.5% for ≥ 80 years) and correlated positively with increasing deprivation.ConclusionsClinical codes indicative of COVID-19 vaccinations being declined are commonly used in England, but substantially more common among black and South Asian people, and in more deprived areas. Qualitative research is needed to determine typical reasons for recorded declines, including to what extent they reflect patients actively declining.