Projected epidemiological consequences of the Omicron SARS-CoV-2 variant in England, December 2021 to April 2022 (preprint)

The Omicron B.1.1.529 SARS-CoV-2 variant was first detected in late November 2021 and has since spread to multiple countries worldwide. We model the potential consequences of the Omicron variant on SARS-CoV-2 transmission and health outcomes in England between December 2021 and April 2022, using a deterministic compartmental model fitted to epidemiological data from March 2020 onwards. Because of uncertainty around the characteristics of Omicron, we explore scenarios varying the extent of Omicron's immune escape and the effectiveness of COVID-19 booster vaccinations against Omicron, assuming the level of Omicron's transmissibility relative to Delta to match the growth in observed S gene target failure data in England. We consider strategies for the re-introduction of control measures in response to projected surges in transmission, as well as scenarios varying the uptake and speed of COVID-19 booster vaccinations and the rate of Omicron's introduction into the population. These results suggest that Omicron has the potential to cause substantial surges in cases, hospital admissions and deaths in populations with high levels of immunity, including England. The reintroduction of additional non-pharmaceutical interventions may be required to prevent hospital admissions exceeding the levels seen in England during the previous peak in winter 2020-2021.

Dosing interval strategies for two-dose COVID-19 vaccination in 13 low- and middle-income countries of Europe: health impact modelling and benefit-risk analysis (preprint)

Background: In settings where the COVID-19 vaccine supply is constrained, extending the intervals between the first and second doses of the COVID-19 vaccine could let more people receive their first doses earlier. Our aim is to estimate the health impact of COVID-19 vaccination alongside benefit-risk assessment of different dosing intervals for low- and middle-income countries of Europe. Methods: We fitted a dynamic transmission model to country-level daily reported COVID-19 mortality in 13 low- and middle-income countries in the World Health Organization European Region (Albania, Armenia, Azerbaijan, Belarus, Bosnia and Herzegovina, Bulgaria, Georgia, Republic of Moldova, Russian Federation, Serbia, North Macedonia, Turkey, and Ukraine). A vaccine product with characteristics similar to the Oxford/AstraZeneca COVID-19 (AZD1222) vaccine was used in the base case scenario and was complemented by sensitivity analyses around efficacies related to other COVID-19 vaccines. Both fixed dosing intervals at 4, 8, 12, 16, and 20 weeks and dose-specific intervals that prioritise specific doses for certain age groups were tested. Optimal intervals minimise COVID-19 mortality between March 2021 and December 2022. We incorporated the emergence of variants of concern into the model, and also conducted a benefit-risk assessment to quantify the trade-off between health benefits versus adverse events following immunisation. Findings: In 12 of the 13 countries, optimal strategies are those that prioritise the first doses among older adults (60+ years) or adults (20-59 years). These strategies lead to dosing intervals longer than six months. In comparison, a four-week fixed dosing interval may incur 10.2% [range: 4.0% - 22.5%; n = 13 (countries)] more deaths. There is generally a negative association between dosing interval and COVID-19 mortality within the range we investigated. Assuming a shorter first dose waning duration of 120 days, as opposed to 360 days in the base case, led to shorter optimal dosing intervals of 8-12 weeks. Benefit-risk ratios were the highest for fixed dosing intervals of 8-12 weeks. Interpretation: We infer that longer dosing intervals of over six months, which are substantially longer than the current label recommendation for most vaccine products, could reduce COVID-19 mortality in low- and middle-income countries of WHO/Europe. Certain vaccine features, such as fast waning of first doses, significantly shorten the optimal dosing intervals.

Behaviour, booster vaccines and waning vaccine protection: modelling the medium-term dynamics of SARS-CoV-2 transmission in England (preprint)

England has experienced a heavy burden of COVID-19, with high infection levels observed throughout the summer months of 2021. Alongside the emergence of evidence suggesting that COVID-19 vaccine protection wanes over time, booster vaccinations began for individuals aged 50 and above in September 2021. Using a model fitted to 18 months of epidemiological data, we project potential dynamics of SARS-CoV-2 transmission in England to September 2022. We consider key uncertainties including behavioural change, waning vaccine protection, strategies for vaccination, and the reintroduction of public health and social measures. We project the current wave of transmission will peak in Autumn 2021, with low levels of transmission in early 2022. The extent to which SARS-CoV-2 transmission resurges in 2022 depends largely on assumptions around waning vaccine protection and booster vaccinations. Widespread booster vaccinations or the reimposition of mild public health and social measures such as work-from-home policies could largely mitigate the wave of COVID-19 transmission projected to occur in England in Spring/Summer 2022.

Optimising health and economic impacts of COVID-19 vaccine prioritisation strategies in the WHO European Region (preprint)

BackgroundCountries in the World Health Organization (WHO) European Region differ in terms of the COVID-19 vaccine roll-out speed. We evaluated the health and economic impact of different age-based vaccine prioritisation strategies across this demographically and socio-economically diverse region. MethodsWe fitted country-specific age-stratified compartmental transmission models to reported COVID-19 mortality in the WHO European Region to inform the immunity level before vaccine roll-out. Building upon broad recommendations from the WHO Strategic Advisory Group of Experts on Immunisation (SAGE), we examined four strategies that prioritise: all adults (V+), younger (20-59 year-olds) followed by older adults (60+) (V20), older followed by younger adults (V60), and the oldest adults (75+) (V75) followed by incremental expansion to successively younger five-year age groups. We explored four roll-out scenarios based on projections or recent observations (R1-4) - the slowest scenario (R1) covers 30% of the total population by December 2022 and the fastest (R4) 80% by December 2021. Five decision-making metrics were summarised over 2021-22: mortality, morbidity, and losses in comorbidity-adjusted life expectancy (cLE), comorbidity- and quality-adjusted life years (cQALY), and the value of human capital (HC). Six sets of infection-blocking and disease-reducing vaccine efficacies were considered. FindingsThe optimal age-based vaccine prioritisation strategies were sensitive to country characteristics, decision-making metrics and roll-out speeds. Overall, V60 consistently performed better than or comparably to V75. There were greater benefits in prioritising older adults when roll-out is slow and when VE is low. Under faster roll-out, V+ was the most desirable option. InterpretationA prioritisation strategy involving more age-based stages (V75) does not necessarily lead to better health and economic outcomes than targeting broad age groups (V60). Countries expecting a slow vaccine roll-out may particularly benefit from prioritising older adults. FundingWorld Health Organization, Bill and Melinda Gates Foundation, the Medical Research Council (United Kingdom), the National Institute of Health Research (United Kingdom), the European Commission, the Foreign, Commonwealth and Development Office (United Kingdom), Wellcome Trust Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSWe searched PubMed and medRxiv for articles published in English from inception to 9 Jun 2021, with the search terms: ("COVID-19" OR "SARS-CoV-2") AND ("priorit*) AND ("model*") AND ("vaccin*") and identified 66 studies on vaccine prioritization strategies. Of the 25 studies that compared two or more age-based prioritisation strategies, 12 found that targeting younger adults minimised infections while targeting older adults minimised mortality; an additional handful of studies found similar outcomes between different age-based prioritisation strategies where large outbreaks had already occurred. However, only two studies have explored age-based vaccine prioritisation using models calibrated to observed outbreaks in more than one country, and no study has explored the effectiveness of vaccine prioritisation strategies across settings with different population structures, contact patterns, and outbreak history. Added-value of this studyWe evaluated various age-based vaccine prioritisation strategies for 38 countries in the WHO European Region using various health and economic outcomes for decision-making, by parameterising models using observed outbreak history, known epidemiologic and vaccine characteristics, and a range of realistic vaccine roll-out scenarios. We showed that while targeting older adults was generally advantageous, broadly targeting everyone above 60 years might perform better than or comparably to a more detailed strategy that targeted the oldest age group above 75 years followed by those in the next younger five-year age band. Rapid vaccine roll-out has only been observed in a small number of countries. If vaccine coverage can reach 80% by the end of 2021, prioritising older adults may not be optimal in terms of health and economic impact. Lower vaccine efficacy was associated with greater relative benefits only under relatively slow roll-out scenarios considered. Implication of all the available evidenceCOVID-19 vaccine prioritization strategies that require more precise targeting of individuals of a specific and narrow age range may not necessarily lead to better outcomes compared to strategies that prioritise populations across broader age ranges. In the WHO European Region, prioritising all adults equally or younger adults first will only optimise health and economic impact when roll-out is rapid, which may raise between-country equity issues given the global demand for COVID-19 vaccines.

Impact of non-pharmaceutical interventions on SARS-CoV-2 outbreaks in English care homes: a modelling study (preprint)

Background COVID-19 outbreaks are still occurring in English care homes despite the non-pharmaceutical interventions (NPIs) in place. Methods We developed a stochastic compartmental model to simulate the spread of SARS-CoV-2 within an English care home. We quantified the outbreak risk under the NPIs already in place, the role of community prevalence in driving outbreaks, and the relative contribution of all importation routes into the care home. We also considered the potential impact of additional control measures, namely: increasing staff and resident testing frequency, using lateral flow antigen testing (LFD) tests instead of PCR, enhancing infection prevention and control (IPC), increasing the proportion of residents isolated, shortening the delay to isolation, improving the effectiveness of isolation, restricting visitors and limiting staff to working in one care home. Findings The model suggests that importation of SARS-CoV-2 by staff, from the community, is the main driver of outbreaks, that importation by visitors or from hospitals is rare, and that the past testing strategy (monthly testing of residents and daily testing of staff by PCR) likely provides negligible benefit in preventing outbreaks. Daily staff testing by LFD was 39% (95% 18-55%) effective in preventing outbreaks at 30 days compared to no testing. Interpretation Increasing the frequency of testing in staff and enhancing IPC are important to preventing importations to the care home. Further work is needed to understand the impact of vaccination in this population, which is likely to be very effective in preventing outbreaks. Funding The National Institute for Health Research, European Union Horizon 2020, Canadian Institutes of Health Research, French National Research Agency, UK Medical Research Council. The World Health Organisation funded the development of the COS-LTCF Shiny application.

Estimated transmissibility and severity of novel SARS-CoV-2 Variant of Concern 202012/01 in England (preprint)

A novel SARS-CoV-2 variant, VOC 202012/01 (lineage B.1.1.7), emerged in southeast England in November 2020 and is rapidly spreading towards fixation. Using a variety of statistical and dynamic modelling approaches, we estimate that this variant has a 43-90% (range of 95% credible intervals 38-130%) higher reproduction number than preexisting variants. A fitted two-strain dynamic transmission model shows that VOC 202012/01 will lead to large resurgences of COVID-19 cases. Without stringent control measures, including limited closure of educational institutions and a greatly accelerated vaccine roll-out, COVID-19 hospitalisations and deaths across England in 2021 will exceed those in 2020. Concerningly, VOC 202012/01 has spread globally and exhibits a similar transmission increase (59-74%) in Denmark, Switzerland, and the United States.