Comparison of the 2021 COVID-19 'Roadmap' Projections against Public Health Data

Control and mitigation of the COVID-19 pandemic in England has relied on a combination of vaccination and non-pharmaceutical interventions (NPIs). Some of these NPIs are extremely costly (economically and socially), so it was important to relax these promptly without overwhelming already burdened health services. The eventual policy was a Roadmap of four relaxation steps throughout 2021, taking England from lock-down to the cessation of all restrictions on social interaction. In a series of six Roadmap documents generated throughout 2021, models assessed the potential risk of each relaxation step. Here we show that the model projections generated a reliable estimation of medium-term hospital admission trends, with the data points up to September 2021 generally lying within our 95% prediction intervals. The greatest uncertainties in the modelled scenarios came from vaccine efficacy estimates against novel variants, and from assumptions about human behaviour in the face of changing restrictions and risk.

Short-term Projections based on Early Omicron Variant Dynamics in England.

Throughout the ongoing COVID-19 pandemic, the worldwide transmission and replication of SARS-COV-2, the causative agent of COVID-19 disease, has resulted in the opportunity for multiple mutations to occur that may alter the virus transmission characteristics, the effectiveness of vaccines and the severity of disease upon infection. The Omicron variant (B.1.1.529) was first reported to the WHO by South Africa on 24 November 2021 and was declared a variant of concern by the WHO on 26 November 2021. The variant was first detected in the UK on 27 November 2021 and has since been reported in a number of countries globally where it is frequently associated with rapid increase in cases. Here we present analyses of UK data showing the earliest signatures of the Omicron variant and mathematical modelling that uses the UK data to simulate the potential impact of this variant in the UK. In order to account for the uncertainty in transmission advantage, vaccine escape and severity at the time of writing, we carry out a sensitivity analysis to assess the impact of these variant characteristics on future risk.

Waning, Boosting and a Path to Endemicity for SARS-CoV-2.

In many countries, an extensive vaccination programme has substantially reduced the public-health impact of SARS-CoV-2, limiting the number of hospital admissions and deaths compared to an unmitigated epidemic. Ensuring a low-risk transition from the current situation to one in which SARS-CoV-2 is endemic requires maintenance of high levels of population immunity. The observed waning of vaccine efficacy over time suggests that booster doses may be required to maintain population immunity especially in the most vulnerable groups. Here, using data and models for England, we consider the dynamics of COVID-19 over a two-year time-frame, and the role that booster vaccinations can play in mitigating the worst effects. We find that boosters are necessary to suppress the imminent wave of infections that would be generated by waning vaccine efficacy. Projecting further into the future, the optimal deployment of boosters is highly sensitive to their long-term action. If protection from boosters wanes slowly (akin to protection following infection) then a single booster dose to the over 50s may be all that is needed over the next two-years. However, if protection wanes more rapidly (akin to protection following second dose vaccination) then annual or even biannual boosters are required to limit subsequent epidemic peaks an reduce the pressure on public health services.

Optimal health and economic impact of non-pharmaceutical intervention measures prior and post vaccination in England: a mathematical modelling study

BackgroundEven with good progress on vaccination, SARS-CoV-2 infections in the UK may continue to impose a high burden of disease and therefore pose substantial challenges for health policy decision makers. Stringent government-mandated physical distancing measures (lockdown) have been demonstrated to be epidemiologically effective, but can have both positive and negative economic consequences. The duration and frequency of any intervention policy could, in theory, could be optimised to maximise economic benefits while achieving substantial reductions in disease. MethodsHere we use a pre-existing SARS-CoV-2 transmission model to assess the health and economic implications of different strengths of control through time in order to identify optimal approaches to non-pharmaceutical intervention stringency in the UK, considering the role of vaccination in reducing the need for future physical distancing measures. The model is calibrated to the COVID-19 epidemic in England and we carry out retrospective analysis of the optimal timing of precautionary breaks in 2020 and the optimal relaxation policy from the January 2021 lockdown, considering the willingness to pay for health improvement. ResultsWe find that the precise timing and intensity of interventions is highly dependent upon the objective of control. As intervention measures are relaxed, we predict a resurgence in cases, but the optimal intervention policy can be established dependent upon the willingness to pay (WTP) per QALY loss avoided. Our results show that establishing an optimal level of control can result in a reduction in net monetary loss of billions of pounds, dependent upon the precise WTP value. ConclusionsIt is vital, as the UK emerges from lockdown, but continues to face an on-going pandemic, to accurately establish the overall health and economic costs when making policy decisions. We demonstrate how some of these can be quantified, employing mechanistic infectious disease transmission models to establish optimal levels of control for the ongoing COVID-19 pandemic.

An analysis of school absences in England during the Covid-19 pandemic

The introduction of SARS-CoV-2, the virus that causes COVID-19 infection, in the UK in early 2020, resulted in the UK government introducing several control policies in order to reduce the spread of disease. As part of these restrictions, schools were closed to all pupils in March (except for vulnerable and key worker children), before re-opening to certain year groups in June. Finally all school children returned to the classroom in September. In this paper, we analyse the data on school absences from September 2020 to December 2020 as a result of COVID-19 infection and how that varied through time as other measures in the community were introduced. We utilise data from the Educational Settings database compiled by the Department for Education and examine how pupil and teacher absences change in both primary and secondary schools. Our results show that absences as a result of COVID-19 infection rose steadily following the re-opening of schools in September. Cases in teachers were seen to decline during the November lockdown, particularly in those regions that had previously been in tier 3, the highest level of control at the time. Cases in secondary school pupils increased for the first two weeks of the November lockdown, before decreasing. Since the introduction of the tier system, the number of absences owing to confirmed infection in primary schools was observed to be significantly lower than in secondary schools across all regions and tiers. In December, we observed a large rise in the number of absences per school in secondary school settings in the South East and Greater London, but such rises were not observed in other regions or in primary school settings. We conjecture that the increased transmissibility of the new variant in these regions may have contributed to this rise in cases in secondary schools. Finally, we observe a positive correlation between cases in the community and cases in schools in most regions, with weak evidence suggesting that cases in schools lag behind cases in the surrounding community. We conclude that there is not significant evidence to suggest that schools are playing a significant role in driving spread in the community and that careful monitoring may be required as schools re-open to determine the effect associated with open schools upon community incidence.

Vaccination and Non-Pharmaceutical Interventions: when can the UK relax about COVID-19?

BackgroundThe announcement of efficacious vaccine candidates against SARS-CoV-2 has been met with worldwide acclaim and relief. Many countries already have detailed plans for vaccine targeting based on minimising severe illness, death and healthcare burdens. Normally, relatively simple relationships between epidemiological parameters, vaccine efficacy and vaccine uptake predict the success of any immunisation programme. However, the dynamics of vaccination against SARS-CoV-2 is made more complex by age-dependent factors, changing levels of infection and the potential relaxation of non-pharmaceutical interventions (NPIs) as the perceived risk declines. MethodsIn this study we use an age-structured mathematical model, matched to a range of epidemiological data in the UK, that also captures the roll-out of a two-dose vaccination programme targeted at specific age groups. FindingsWe consider the interaction between the UK vaccination programme and future relaxation (or removal) of NPIs. Our predictions highlight the population-level risks of early relaxation leading to a pronounced wave of infection, hospital admissions and deaths. Only vaccines that offer high infection-blocking efficacy with high uptake in the general population allow relaxation of NPIs without a huge surge in deaths. InterpretationWhile the novel vaccines against SARS-CoV-2 offer a potential exit strategy for this outbreak, this is highly contingent on the infection-blocking (or transmission-blocking) action of the vaccine and the population uptake, both of which need to be carefully monitored as vaccine programmes are rolled out in the UK and other countries. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSVaccination has been seen as a key tool in the fight against SARS-CoV-2. The vaccines already developed represent a major technological achievement and have been shown to generate significant immune responses, as well as offering considerable protection against disease. However, to date there is limited information on the degree of infection-blocking these vaccines are likely to induce. Mathematical models have already successfully been used to consider age- and risk-structured targeting of vaccination, highlighting the importance of prioritising older and high-risk individuals. Added value of this studyTranslating current knowledge and uncertainty of vaccine behaviour into meaningful public health messages requires models that fully capture the within-country epidemiology as well as the complex roll-out of a two-dose vaccination programme. We show that under reasonable assumptions for vaccine efficacy and uptake the UK is unlikely to reach herd immunity, which means that non-pharmaceutical interventions cannot be released without generating substantial waves of infection. Implications of all the available evidenceVaccination is likely to provide substantial individual protection to those receiving two doses, but the degree of protection to the wider population is still uncertain. While substantial immunisation of the most vulnerable groups will allow for some relaxation of controls, this must be done gradually to prevent large scale public health consequences.

Short-term forecasts to inform the response to the COVID-19 epidemic in the UK

BackgroundShort-term forecasts of infectious disease can aid situational awareness and planning for outbreak response. Here, we report on multi-model forecasts of Covid-19 in the UK that were generated at regular intervals starting at the end of March 2020, in order to monitor expected healthcare utilisation and population impacts in real time. MethodsWe evaluated the performance of individual model forecasts generated between 24 March and 14 July 2020, using a variety of metrics including the weighted interval score as well as metrics that assess the calibration, sharpness, bias and absolute error of forecasts separately. We further combined the predictions from individual models into ensemble forecasts using a simple mean as well as a quantile regression average that aimed to maximise performance. We compared model performance to a null model of no change. ResultsIn most cases, individual models performed better than the null model, and ensembles models were well calibrated and performed comparatively to the best individual models. The quantile regression average did not noticeably outperform the mean ensemble. ConclusionsEnsembles of multi-model forecasts can inform the policy response to the Covid-19 pandemic by assessing future resource needs and expected population impact of morbidity and mortality.

COVID-19 reopening strategies at the county level in the face of uncertainty: Multiple Models for Outbreak Decision Support

Policymakers make decisions about COVID-19 management in the face of considerable uncertainty. We convened multiple modeling teams to evaluate reopening strategies for a mid-sized county in the United States, in a novel process designed to fully express scientific uncertainty while reducing linguistic uncertainty and cognitive biases. For the scenarios considered, the consensus from 17 distinct models was that a second outbreak will occur within 6 months of reopening, unless schools and non-essential workplaces remain closed. Up to half the population could be infected with full workplace reopening; non-essential business closures reduced median cumulative infections by 82%. Intermediate reopening interventions identified no win-win situations; there was a trade-off between public health outcomes and duration of workplace closures. Aggregate results captured twice the uncertainty of individual models, providing a more complete expression of risk for decision-making purposes.

Precautionary breaks: planned, limited duration circuit breaks to control the prevalence of COVID-19

The COVID-19 pandemic in the UK has been characterised by periods of exponential growth and decline, as different non-pharmaceutical interventions (NPIs) are brought into play. During the early uncontrolled phase of the outbreak (early March 2020) there was a period of prolonged exponential growth with epidemiological observations such as hospitalisation doubling every 3-4 days (growth rate r {approx} 0.2). The enforcement of strict lockdown measures led to a noticeable decline in all epidemic quantities (r {approx} -0.06) that slowed during the summer as control measures were relaxed (r {approx} -0.02). Since August, infections, hospitalisations and deaths have been rising (precise estimation of the current growth rate is difficult due to extreme regional heterogeneity and temporal lags between the different epidemiological observations) and various NPIs have been applied locally throughout the UK in response. Controlling any rise in infection is a compromise between public health and societal costs, with more stringent NPIs reducing cases but damaging the economy and restricting freedoms. Currently, NPI imposition is made in response to the epidemiological state, are of indefinite length and are often imposed at short notice, greatly increasing the negative impact. An alternative approach is to consider planned, limited duration periods of strict NPIs aiming to purposefully reduce prevalence before such emergency NPIs are required. These "precautionary breaks" may offer a means of keeping control of the epidemic, while their fixed duration and the forewarning may limit their society impact. Here, using simple analysis and age-structured models matched to the unfolding UK epidemic, we investigate the action of precautionary breaks. In particular we consider their impact on the prevalence of infection, as well as the total number of predicted hospitalisations and deaths. We find that precautionary breaks provide the biggest gains when the growth rate is low, but offer a much needed brake on increasing infection when the growth rate is higher, potentially allowing other measures (such as contact tracing) to regain control.

Modelling SARS-CoV-2 transmission in a UK university setting

Around 40% of school leavers in the UK attend university and individual universities generally host thousands of students each academic year. Bringing together these student communities during the COVID-19 pandemic may require strong interventions to control transmission. Prior modelling analyses of SARS-CoV-2 transmission within universities using compartmental modelling approaches suggest that outbreaks are almost inevitable. We constructed a network-based model to capture the interactions of a student population in different settings (housing, social and study). For a single academic term of a representative campus-based university, we ran a susceptible-latent-infectious-recovered type epidemic process, parameterised according to available estimates for SARS-CoV-2. We investigated the impact of: adherence to (or effectiveness of) isolation and test and trace measures; room isolation of symptomatic students; and supplementary mass testing. With all adhering to test, trace and isolation measures, we found that 22% (7% - 41%) of the student population could be infected during the autumn term, compared to 69% (56% - 76%) when assuming zero adherence to such measures. Irrespective of the adherence to isolation measures, on average a higher proportion of students resident on-campus became infected compared to students resident off-campus. Room isolation generated minimal benefits. Regular mass testing, together with high adherence to isolation and test and trace measures, could substantially reduce the proportion infected during the term compared to having no testing. Our findings suggest SARS-CoV-2 may readily transmit in a university setting if there is limited adherence to nonpharmaceutical interventions and/or there are delays in receiving test results. Following isolation guidance and effective contact tracing curbed transmission and reduced the expected time an adhering student would spend in isolation.

Modelling optimal vaccination strategy for SARS-CoV-2.

The COVID-19 outbreak has highlighted our vulnerability to novel infections. Faced with this threat and no effective treatment, in line with many other countries, the UK adopted enforced social distancing (lockdown) to reduce transmission- successfully reducing the reproductive number, R, below one. However, given the large pool of susceptible individuals that remain, complete relaxation of controls is likely to generate a substantial second wave. Vaccination remains the only foreseeable means of both containing the infection and returning to normal interactions and behaviour. Here, we consider the optimal targeting of vaccination within the UK, with the aim of minimising future deaths or quality adjusted life year (QALY) losses. We show that, for a range of assumptions on the action and efficacy of the vaccine, targeting older age groups first is optimal and can avoid a second wave if the vaccine prevents transmission as well as disease.

Predictions of COVID-19 dynamics in the UK: short-term forecasting and analysis of potential exit strategies

BackgroundEfforts to suppress transmission of SARS-CoV-2 in the UK have seen non-pharmaceutical interventions being invoked. The most severe measures to date include all restaurants, pubs and cafes being ordered to close on 20th March, followed by a "stay at home" order on the 23rd March and the closure of all non-essential retail outlets for an indefinite period. Government agencies are presently analysing how best to develop an exit strategy from these measures and to determine how the epidemic may progress once measures are lifted. Mathematical models are currently providing short and long term forecasts regarding the future course of the COVID-19 outbreak in the UK to support evidence-based policymaking. MethodsWe present a deterministic, age-structured transmission model that uses real-time data on confirmed cases requiring hospital care and mortality to provide up-to-date predictions on epidemic spread in ten regions of the UK. The model captures a range of age-dependent heterogeneities, reduced transmission from asymptomatic infections and produces a good fit to the key epidemic features over time. We simulated a suite of scenarios to assess the impact of differing approaches to relaxing social distancing measures from 7th May 2020, on the estimated number of patients requiring inpatient and critical care treatment, and deaths. With regard to future epidemic outcomes, we investigated the impact of reducing compliance, ongoing shielding of elder age groups, reapplying stringent social distancing measures using region based triggers and the role of asymptomatic transmission. FindingsWe find that significant relaxation of social distancing measures from 7th May onwards can lead to a rapid resurgence of COVID-19 disease and the health system being quickly overwhelmed by a sizeable, second epidemic wave. In all considered age-shielding based strategies, we projected serious demand on critical care resources during the course of the pandemic. The reintroduction and release of strict measures on a regional basis, based on ICU bed occupancy, results in a long epidemic tail, until the second half of 2021, but ensures that the health service is protected by reintroducing social distancing measures for all individuals in a region when required. DiscussionOur work confirms the effectiveness of stringent non-pharmaceutical measures in March 2020 to suppress the epidemic. It also provides strong evidence to support the need for a cautious, measured approach to relaxation of lockdown measures, to protect the most vulnerable members of society and support the health service through subduing demand on hospital beds, in particular bed occupancy in intensive care units.