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.

Figure 1

Trajectory of the COVID-19 epidemic in England and the emergence of the delta variant Observed (grey points) daily hospital admissions (A), log hospital admissions (B), hospital deaths (C), and log hospital deaths (D). The blue line shows the model fit up to July 19, 2021, and the red and purple lines show the projected admissions and deaths assuming a central vaccine effectiveness, cross-immunity, and immunity duration and a gradual increase in contacts and a return to high (dark red), moderate (light red), or low (purple) transmissibility (contact rates) after non-pharmaceutical interventions are lifted. The shaded area is the 95% credible interval. Note that the central projected trend is the median across all daily projections and is not a single trajectory. The yellow points in panels A–D show the most recent data (July 19–Sept 16, 2021), which were not fitted to. (E) Model fit to the daily proportion of cases due to the delta variant (variant and mutation data) over time from March 8–July 19, 2021, in London as an example (appendix p 54 shows other regions). Points show the data, bars are 95% CIs, the blue line is the model fit, and the shaded area is the 95% credible interval. (F) Estimated delta seeding date by UK National Health Service region. Points show the median estimate and horizontal bars show the 95% credible interval.

Figure 2

Prevalence-weighted effective R(t) and R(t) excluding infection-induced or vaccine-induced immunity (A) and proportion of the population in England protected after infection or vaccination against infection, severe disease, or death (B), over time (A) Estimated values from the end of the second national lockdown up to July 19, 2021, and assumed values thereafter. The solid line shows the median R(t) and the shaded area shows the 95% credible interval. Shaded area shows school holidays—note we do not explicitly model the impact of school closures for the period July 23–Aug 31 in order to capture the overall gradual increase in contacts from July 19 to Oct 1 (appendix p 44). The forward projection section of the figure corresponds to the central immunity and gradual return to moderate mixing scenario. Note that our central projected trend is the median across all daily projections and is not a single trajectory. (B) Proportion of the English population, from Jan 1, 2021, protected after infection or vaccination over time against infection, severe disease, or death. The vertical dashed line shows the separation between the observed vaccination schedule up to July 31, followed by the simulated schedule assuming central immunity and a gradual return to moderate transmissibility after non-pharmaceutical restrictions are lifted. The white space in the plot corresponds to individuals who have neither been vaccinated against nor infected with SARS-CoV-2. R(t)=reproduction number. *Euro 2020 football tournament.

Figure 3

England COVID-19 daily infections (A), hospital admissions (B), deaths (C), and total additional deaths between June 21, 2021, and Jan 1, 2022 (D) Assumptions were that all remaining NPIs were lifted on June 21 (blue) or July 19 (red and purple) with a gradual increase in contacts over 11 weeks thereafter, and a return to low (light blue or purple), moderate (medium blue or red), or high (dark blue or red) transmissibility (contact rates). The grey points show the fitted data and yellow the most recent trends (July 19–Sept 16, not fitted). Each column shows projections assuming delta variant with optimistic (left column); central (middle column); and pessimistic (right column) vaccine effectiveness, cross-protection, and waning immunity assumptions (appendix pp 9, 38). The plots are truncated on Jan 1, 2022, but model results in the main text are based on simulations up to June 1, 2022. The central projected trend is the median across all daily projections and is not a single trajectory. Shading shows 95% credible intervals.