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 further outbreak. 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 may be sufficient to stem the epidemic if the vaccine prevents transmission as well as disease.

Efforts 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. We 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. We 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. Our 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.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused considerable morbidity and mortality worldwide. The protection provided by vaccines and booster doses offered a method of mitigating severe clinical outcomes and mortality. However, by the end of 2021, the global distribution of vaccines was highly heterogeneous, with some countries gaining over 90% coverage in adults, whereas others reached less than 2%. In this study, we used an age-structured model of SARS-CoV-2 dynamics, matched to national data from 152 countries in 2021, to investigate the global impact of different potential vaccine sharing protocols that attempted to address this inequity. We quantified the effects of implemented vaccine rollout strategies on the spread of SARS-CoV-2, the subsequent global burden of disease and the emergence of novel variants. We found that greater vaccine sharing would have lowered the total global burden of disease, and any associated increases in infections in previously vaccine-rich countries could have been mitigated by reduced relaxation of non-pharmaceutical interventions. Our results reinforce the health message, pertinent to future pandemics, that vaccine distribution proportional to wealth, rather than to need, may be detrimental to all.

Viral reproduction of SARS-CoV-2 provides opportunities for the acquisition of advantageous mutations, altering viral transmissibility, disease severity, and/or allowing escape from natural or vaccine-derived immunity. We use three mathematical models: a parsimonious deterministic model with homogeneous mixing; an age-structured model; and a stochastic importation model to investigate the effect of potential variants of concern (VOCs). Calibrating to the situation in England in May 2021, we find epidemiological trajectories for putative VOCs are wide-ranging and dependent on their transmissibility, immune escape capability, and the introduction timing of a postulated VOC-targeted vaccine. We demonstrate that a VOC with a substantial transmission advantage over resident variants, or with immune escape properties, can generate a wave of infections and hospitalisations comparable to the winter 2020-2021 wave. Moreover, a variant that is less transmissible, but shows partial immune-escape could provoke a wave of infection that would not be revealed until control measures are further relaxed.

By mid-May 2020, cases of COVID-19 in the UK had been declining for over a month; a multi-phase emergence from lockdown was planned, including a scheduled partial reopening of schools on 1 June 2020. Although evidence suggests that children generally display mild symptoms, the size of the school-age population means the total impact of reopening schools is unclear. Here, we present work from mid-May 2020 that focused on the imminent opening of schools and consider what these results imply for future policy. We compared eight strategies for reopening primary and secondary schools in England. Modifying a transmission model fitted to UK SARS-CoV-2 data, we assessed how reopening schools affects contact patterns, anticipated secondary infections and the relative change in the reproduction number, R. We determined the associated public health impact and its sensitivity to changes in social distancing within the wider community. We predicted that reopening schools with half-sized classes or focused on younger children was unlikely to push R above one. Older children generally have more social contacts, so reopening secondary schools results in more cases than reopening primary schools, while reopening both could have pushed R above one in some regions. Reductions in community social distancing were found to outweigh and exacerbate any impacts of reopening. In particular, opening schools when the reproduction number R is already above one generates the largest increase in cases. Our work indicates that while any school reopening will result in increased mixing and infection amongst children and the wider population, reopening schools alone in June 2020 was unlikely to push R above one. Ultimately, reopening decisions are a difficult trade-off between epidemiological consequences and the emotional, educational and developmental needs of children. Into the future, there are difficult questions about what controls can be instigated such that schools can remain open if cases increase. This article is part of the theme issue ‘Modelling that shaped the early COVID-19 pandemic response in the UK’.

The rapid emergence of SARS-CoV-2 mutants with new phenotypic properties is a critical challenge to the control of the ongoing pandemic. B.1.1.7 was monitored in the UK through routine testing and S-gene target failures (SGTF), comprising over 90% of cases by March 2021. Now, the reverse is occurring: SGTF cases are being replaced by an S-gene positive variant, which we associate with B.1.617.2. Evidence from the characteristics of S-gene positive cases demonstrates that, following importation, B.1.617.2 is transmitted locally, growing at a rate higher than B.1.1.7 and a doubling time between 5-14 days. S-gene positive cases should be prioritised for sequencing and aggressive control in any countries in which this variant is newly detected. One-Sentence Summary The B.1.617.2 variant of SARS-CoV-2 is replacing B.1.1.7 and emerging as the dominant variant in England, evidenced by sustained local transmission.