Dataset Information

Non-pharmaceutical interventions, vaccination, and the SARS-CoV-2 delta variant in England: a mathematical modelling study.

ABSTRACT:

Background

England's COVID-19 roadmap out of lockdown policy set out the timeline and conditions for the stepwise lifting of non-pharmaceutical interventions (NPIs) as vaccination roll-out continued, with step one starting on March 8, 2021. In this study, we assess the roadmap, the impact of the delta (B.1.617.2) variant of SARS-CoV-2, and potential future epidemic trajectories.

Methods

This mathematical modelling study was done to assess the UK Government's four-step process to easing lockdown restrictions in England, UK. We extended a previously described model of SARS-CoV-2 transmission to incorporate vaccination and multi-strain dynamics to explicitly capture the emergence of the delta variant. We calibrated the model to English surveillance data, including hospital admissions, hospital occupancy, seroprevalence data, and population-level PCR testing data using a Bayesian evidence synthesis framework, then modelled the potential trajectory of the epidemic for a range of different schedules for relaxing NPIs. We estimated the resulting number of daily infections and hospital admissions, and daily and cumulative deaths. Three scenarios spanning a range of optimistic to pessimistic vaccine effectiveness, waning natural immunity, and cross-protection from previous infections were investigated. We also considered three levels of mixing after the lifting of restrictions.

Findings

The roadmap policy was successful in offsetting the increased transmission resulting from lifting NPIs starting on March 8, 2021, with increasing population immunity through vaccination. However, because of the emergence of the delta variant, with an estimated transmission advantage of 76% (95% credible interval [95% CrI] 69-83) over alpha, fully lifting NPIs on June 21, 2021, as originally planned might have led to 3900 (95% CrI 1500-5700) peak daily hospital admissions under our central parameter scenario. Delaying until July 19, 2021, reduced peak hospital admissions by three fold to 1400 (95% CrI 700-1700) per day. There was substantial uncertainty in the epidemic trajectory, with particular sensitivity to the transmissibility of delta, level of mixing, and estimates of vaccine effectiveness.

Interpretation

Our findings show that the risk of a large wave of COVID-19 hospital admissions resulting from lifting NPIs can be substantially mitigated if the timing of NPI relaxation is carefully balanced against vaccination coverage. However, with the delta variant, it might not be possible to fully lift NPIs without a third wave of hospital admissions and deaths, even if vaccination coverage is high. Variants of concern, their transmissibility, vaccine uptake, and vaccine effectiveness must be carefully monitored as countries relax pandemic control measures.

Funding

National Institute for Health Research, UK Medical Research Council, Wellcome Trust, and UK Foreign, Commonwealth and Development Office.

SUBMITTER: Sonabend R

PROVIDER: S-EPMC8550916 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundThe dynamics of vaccination against SARS-CoV-2 are complicated by age-dependent factors, changing levels of infection, and the relaxation of non-pharmaceutical interventions (NPIs) as the perceived risk declines, necessitating the use of mathematical models. Our aims were to use epidemiological data from the UK together with estimates of vaccine efficacy to predict the possible long-term dynamics of SARS-CoV-2 under the planned vaccine rollout.MethodsIn this study, we used a mathematical model structured by age and UK region, fitted to a range of epidemiological data in the UK, which incorporated the planned rollout of a two-dose vaccination programme (doses 12 weeks apart, protection onset 14 days after vaccination). We assumed default vaccine uptake of 95% in those aged 80 years and older, 85% in those aged 50-79 years, and 75% in those aged 18-49 years, and then varied uptake optimistically and pessimistically. Vaccine efficacy against symptomatic disease was assumed to be 88% on the basis of Pfizer-BioNTech and Oxford-AstraZeneca vaccines being administered in the UK, and protection against infection was varied from 0% to 85%. We considered the combined interaction of the UK vaccination programme with multiple potential future relaxations (or removals) of NPIs, to predict the reproduction number (R) and pattern of daily deaths and hospital admissions due to COVID-19 from January, 2021, to January, 2024.FindingsWe estimate that vaccination alone is insufficient to contain the outbreak. In the absence of NPIs, even with our most optimistic assumption that the vaccine will prevent 85% of infections, we estimate R to be 1·58 (95% credible intervals [CI] 1·36-1·84) once all eligible adults have been offered both doses of the vaccine. Under the default uptake scenario, removal of all NPIs once the vaccination programme is complete is predicted to lead to 21 400 deaths (95% CI 1400-55 100) due to COVID-19 for a vaccine that prevents 85% of infections, although this number increases to 96 700 deaths (51 800-173 200) if the vaccine only prevents 60% of infections. Although vaccination substantially reduces total deaths, it only provides partial protection for the individual; we estimate that, for the default uptake scenario and 60% protection against infection, 48·3% (95% CI 48·1-48·5) and 16·0% (15·7-16·3) of deaths will be in individuals who have received one or two doses of the vaccine, respectively.InterpretationFor all vaccination scenarios we investigated, our predictions highlight the risks associated with early or rapid relaxation of NPIs. Although novel vaccines against SARS-CoV-2 offer a potential exit strategy for the pandemic, success is highly contingent on the precise vaccine properties and population uptake, both of which need to be carefully monitored.FundingNational Institute for Health Research, Medical Research Council, and UK Research and Innovation.

Project description:BackgroundIn countries with high COVID-19 vaccination rates the SARS-CoV-2 Delta variant resulted in rapidly increasing case numbers. This study evaluated the use of non-pharmaceutical interventions (NPIs) coupled with alternative vaccination strategies to determine feasible Delta mitigation strategies for Australia. We aimed to understand the potential effectiveness of high vaccine coverage levels together with NPI physical distancing activation and to establish the benefit of adding children and adolescents to the vaccination program. Border closure limited SARS-CoV-2 transmission in Australia; however, slow vaccination uptake resulted in Delta outbreaks in the two largest cities and may continue as international travel increases.MethodsAn agent-based model was used to evaluate the potential reduction in the COVID-19 health burden resulting from alternative vaccination strategies. We assumed immunity was derived from vaccination with the BNT162b2 Pfizer BioNTech vaccine. Two age-specific vaccination strategies were evaluated, ages 5 and above, and 12 and above, and the health burden determined under alternative vaccine coverages, with/without activation of NPIs. Age-specific infections generated by the model, together with recent UK data, permitted reductions in the health burden to be quantified.ResultsCases, hospitalisations and deaths are shown to reduce by (i) increasing coverage to include children aged 5 to 11 years, (ii) activating moderate NPI measures and/or (iii) increasing coverage levels above 80%. At 80% coverage, vaccinating ages 12 and above without NPIs is predicted to result in 1095 additional hospitalisations per million population; adding ages 5 and above reduces this to 996 per million population. Activating moderate NPIs reduces hospitalisations to 611 for ages 12 and over, and 382 per million for ages 5 and above. Alternatively, increasing coverage to 90% for those aged 12 and above is estimated to reduce hospitalisations to 616. Combining all three measures is shown to reduce cases to 158, hospitalisations to 1 and deaths to zero, per million population.ConclusionsDelta variant outbreaks may be managed by vaccine coverage rates higher than 80% and activation of moderate NPI measures, preventing healthcare facilities from being overwhelmed. If 90% coverage cannot be achieved, including young children and adolescents in the vaccination program coupled with activation of moderate NPIs appears necessary to suppress future COVID-19 Delta-like transmission and prevent intensive care unit surge capacity from being exceeded.

Project description:BackgroundSince its emergence in Autumn 2020, the SARS-CoV-2 Variant of Concern (VOC) B.1.1.7 (WHO label Alpha) rapidly became the dominant lineage across much of Europe. Simultaneously, several other VOCs were identified globally. Unlike B.1.1.7, some of these VOCs possess mutations thought to confer partial immune escape. Understanding when and how these additional VOCs pose a threat in settings where B.1.1.7 is currently dominant is vital.MethodsWe examine trends in the prevalence of non-B.1.1.7 lineages in London and other English regions using passive-case detection PCR data, cross-sectional community infection surveys, genomic surveillance, and wastewater monitoring. The study period spans from 31st January 2021 to 15th May 2021.FindingsAcross data sources, the percentage of non-B.1.1.7 variants has been increasing since late March 2021. This increase was initially driven by a variety of lineages with immune escape. From mid-April, B.1.617.2 (WHO label Delta) spread rapidly, becoming the dominant variant in England by late May.InterpretationThe outcome of competition between variants depends on a wide range of factors such as intrinsic transmissibility, evasion of prior immunity, demographic specificities and interactions with non-pharmaceutical interventions. The presence and rise of non-B.1.1.7 variants in March likely was driven by importations and some community transmission. There was competition between non-B.1.17 variants which resulted in B.1.617.2 becoming dominant in April and May with considerable community transmission. Our results underscore that early detection of new variants requires a diverse array of data sources in community surveillance. Continued real-time information on the highly dynamic composition and trajectory of different SARS-CoV-2 lineages is essential to future control efforts.FundingNational Institute for Health Research, Medicines and Healthcare products Regulatory Agency, DeepMind, EPSRC, EA Funds programme, Open Philanthropy, Academy of Medical Sciences Bill,Melinda Gates Foundation, Imperial College Healthcare NHS Trust, The Novo Nordisk Foundation, MRC Centre for Global Infectious Disease Analysis, Community Jameel, Cancer Research UK, Imperial College COVID-19 Research Fund, Medical Research Council, Wellcome Sanger Institute.

Project description:Waning humoral immunity after mRNA vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a significant problem for public health. Breakthrough infection in hospitals over several months after vaccination has not been fully characterized, especially against the delta (B.1.617.2) variant. Here, we describe an outbreak in our hospital in September of 2021, mainly through serological evaluation of the breakthrough infection. This retrospective observational study was done at an emergency and acute care hospital with 204 beds and 486 staff members where most staff members (92.6%) had had their second BNT162b2 vaccination by May of 2021. The peri-infection anti-spike RBD protein IgG (anti-S IgG) titers (lowest values between 11 days before and 7 days after onset or diagnosis) of serum samples from the breakthrough-infected persons were quantified. We also logarithmically estimated the anti-S IgG titers during the exposure period in September of uninfected staff members from their samples collected in May and December 2021. Whole-genome sequencing was done on obtained samples. In this outbreak, twelve persons (ten inpatients and two staff members) were diagnosed with SARS-CoV-2 infection by Loop-Mediated Isothermal Amplification (LAMP) or RT-PCR, eight of whom had been vaccinated twice. Peri-infection anti-S IgG titers could be determined in seven of the eight breakthrough cases, with a geometric mean titer (GMT) of 1,034 AU/ml (95% confidence interval [CI], 398 to 2,686). Among 289 uninfected staff members with data from the two sampling points, the GMT of the estimated anti-S IgG titers during the exposure period in 51 staff members, who were working at the outbreak ward and potentially exposed but uninfected, and 238 other unexposed staff members were 1,458 AU/ml (95% CI, 1,196 to 1,777) and 1,628 AU/ml (95% CI, 1,500 to 1,766), respectively. All viruses from the eight samples for which whole-genome sequencing was available were identified as delta variants. Of the infected persons, one remained asymptomatic throughout the course of treatment, and eleven had an illness of mild to moderate severity, including ten who received monoclonal antibody cocktail (Casirivimab/imdevimab) therapy. Measurement and estimation of anti-spike antibody levels after SARS-CoV-2 vaccination would be helpful for evaluating the risk of breakthrough infection and for determining the necessity of booster vaccination.