Agent-based modelling of reactive vaccination of workplaces and schools against COVID-19.

With vaccination against COVID-19 stalled in some countries, increasing vaccine accessibility and distribution could help keep transmission under control. Here, we study the impact of reactive vaccination targeting schools and workplaces where cases are detected, with an agent-based model accounting for COVID-19 natural history, vaccine characteristics, demographics, behavioural changes and social distancing. In most scenarios, reactive vaccination leads to a higher reduction in cases compared with non-reactive strategies using the same number of doses. The reactive strategy could however be less effective than a moderate/high pace mass vaccination program if initial vaccination coverage is high or disease incidence is low, because few people would be vaccinated around each case. In case of flare-ups, reactive vaccination could better mitigate spread if it is implemented quickly, is supported by enhanced test-trace-isolate and triggers an increased vaccine uptake. These results provide key information to plan an adaptive vaccination rollout.

Impact of booster vaccination on the control of COVID-19 Delta wave in the context of waning immunity: application to France in the winter 2021/22.

Europe has experienced a large COVID-19 wave caused by the Delta variant in winter 2021/22. Using mathematical models applied to Metropolitan France, we find that boosters administered to ≥ 65, ≥ 50 or ≥ 18 year-olds may reduce the hospitalisation peak by 25%, 36% and 43% respectively, with a delay of 5 months between second and third dose. A 10% reduction in transmission rates might further reduce it by 41%, indicating that even small increases in protective behaviours may be critical to mitigate the wave.

SARS-CoV-2 transmission across age groups in France and implications for control.

The shielding of older individuals has been proposed to limit COVID-19 hospitalizations while relaxing general social distancing in the absence of vaccines. Evaluating such approaches requires a deep understanding of transmission dynamics across ages. Here, we use detailed age-specific case and hospitalization data to model the rebound in the French epidemic in summer 2020, characterize age-specific transmission dynamics and critically evaluate different age-targeted intervention measures in the absence of vaccines. We find that while the rebound started in young adults, it reached individuals aged ≥80 y.o. after 4 weeks, despite substantial contact reductions, indicating substantial transmission flows across ages. We derive the contribution of each age group to transmission. While shielding older individuals reduces mortality, it is insufficient to allow major relaxations of social distancing. When the epidemic remains manageable (R close to 1), targeting those most contributing to transmission is better than shielding at-risk individuals. Pandemic control requires an effort from all age groups.

A modelling study investigating short and medium-term challenges for COVID-19 vaccination: From prioritisation to the relaxation of measures.

BACKGROUND: The roll-out of COVID-19 vaccines is a multi-faceted challenge whose performance depends on pace of vaccination, vaccine characteristics and heterogeneities in individual risks. METHODS: We developed a mathematical model accounting for the risk of severe disease by age and comorbidity, and transmission dynamics. We compared vaccine prioritisation strategies in the early roll-out stage and quantified the extent to which measures could be relaxed as a function of the vaccine coverage achieved in France. FINDINGS: Prioritizing at-risk individuals reduces morbi-mortality the most if vaccines only reduce severity, but is of less importance if vaccines also substantially reduce infectivity or susceptibility. Age is the most important factor to consider for prioritization; additionally accounting for comorbidities increases the performance of the campaign in a context of scarce resources. Vaccinating 90% of ≥65 y.o. and 70% of 18-64 y.o. before autumn 2021 with a vaccine that reduces severity by 90% and susceptibility by 80%, we find that control measures reducing transmission rates by 15-27% should be maintained to remain below 1000 daily hospital admissions in France with a highly transmissible variant (basic reproduction number R0  = 4). Assuming 90% of ≥65 y.o. are vaccinated, full relaxation of control measures might be achieved with a vaccine coverage of 89-100% in 18-64 y.o or 60-69% of 0-64 y.o. INTERPRETATION: Age and comorbidity-based vaccine prioritization strategies could reduce the burden of the disease. Very high vaccination coverage may be required to completely relax control measures. Vaccination of children, if possible, could lower coverage targets necessary to achieve this objective.

Benefits and risks associated with different uses of the COVID-19 vaccine Vaxzevria: a modelling study, France, May to September 2021.

Thrombosis with thrombocytopenia (TTS) has been identified as a rare adverse event following COVID-19 vaccination with Vaxzevria. We modelled the benefits and risks of Vaxzevria distribution from May to September 2021 in metropolitan France where other vaccines are available, considering French hospitalisation data and European data on TTS. Across different scenarios, benefits of Vaxzevria distribution in people 55 years and older exceeded the risk of death from COVID-19. In young adults, risks were at least of similar magnitude as benefits.

Lockdown as a last resort option in case of COVID-19 epidemic rebound: a modelling study.

BackgroundGiven its high economic and societal cost, policymakers might be reluctant to implement a large-scale lockdown in case of coronavirus disease (COVID-19) epidemic rebound. They may consider it as a last resort option if alternative control measures fail to reduce transmission.AimWe developed a modelling framework to ascertain the use of lockdown to ensure intensive care unit (ICU) capacity does not exceed a peak target defined by policymakers.MethodsWe used a deterministic compartmental model describing transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the trajectories of COVID-19 patients in healthcare settings, accounting for age-specific mixing patterns and an increasing probability of severe outcomes with age. The framework is illustrated in the context of metropolitan France.ResultsThe daily incidence of ICU admissions and the number of occupied ICU beds are the most robust indicators to decide when a lockdown should be triggered. When the doubling time of hospitalisations estimated before lockdown is between 8 and 20 days, lockdown should be enforced when ICU admissions reach 3.0-3.7 and 7.8-9.5 per million for peak targets of 62 and 154 ICU beds per million (4,000 and 10,000 beds for metropolitan France), respectively. When implemented earlier, the lockdown duration required to get back below a desired level is also shorter.ConclusionsWe provide simple indicators and triggers to decide if and when a last-resort lockdown should be implemented to avoid saturation of ICU. These metrics can support the planning and real-time management of successive COVID-19 pandemic waves.

Monitoring the proportion of the population infected by SARS-CoV-2 using age-stratified hospitalisation and serological data: a modelling study.

BACKGROUND: Regional monitoring of the proportion of the population who have been infected by SARS-CoV-2 is important to guide local management of the epidemic, but is difficult in the absence of regular nationwide serosurveys. We aimed to estimate in near real time the proportion of adults who have been infected by SARS-CoV-2. METHODS: In this modelling study, we developed a method to reconstruct the proportion of adults who have been infected by SARS-CoV-2 and the proportion of infections being detected, using the joint analysis of age-stratified seroprevalence, hospitalisation, and case data, with deconvolution methods. We developed our method on a dataset consisting of seroprevalence estimates from 9782 participants (aged ≥20 years) in the two worst affected regions of France in May, 2020, and applied our approach to the 13 French metropolitan regions over the period March, 2020, to January, 2021. We validated our method externally using data from a national seroprevalence study done between May and June, 2020. FINDINGS: We estimate that 5·7% (95% CI 5·1-6·4) of adults in metropolitan France had been infected with SARS-CoV-2 by May 11, 2020. This proportion remained stable until August, 2020, and increased to 14·9% (13·2-16·9) by Jan 15, 2021. With 26·5% (23·4-29·8) of adult residents having been infected in Île-de-France (Paris region) compared with 5·1% (4·5-5·8) in Brittany by January, 2021, regional variations remained large (coefficient of variation [CV] 0·50) although less so than in May, 2020 (CV 0·74). The proportion infected was twice as high (20·4%, 15·6-26·3) in 20-49-year-olds than in individuals aged 50 years or older (9·7%, 6·9-14·1). 40·2% (34·3-46·3) of infections in adults were detected in June to August, 2020, compared with 49·3% (42·9-55·9) in November, 2020, to January, 2021. Our regional estimates of seroprevalence were strongly correlated with the external validation dataset (coefficient of correlation 0·89). INTERPRETATION: Our simple approach to estimate the proportion of adults that have been infected with SARS-CoV-2 can help to characterise the burden of SARS-CoV-2 infection, epidemic dynamics, and the performance of surveillance in different regions. FUNDING: EU RECOVER, Agence Nationale de la Recherche, Fondation pour la Recherche Médicale, Institut National de la Santé et de la Recherche Médicale (Inserm).

Evaluating the impact of curfews and other measures on SARS-CoV-2 transmission in French Guiana.

While general lockdowns have proven effective to control SARS-CoV-2 epidemics, they come with enormous costs for society. It is therefore essential to identify control strategies with lower social and economic impact. Here, we report and evaluate the control strategy implemented during a large SARS-CoV-2 epidemic in June-July 2020 in French Guiana that relied on curfews, targeted lockdowns, and other measures. We find that the combination of these interventions coincided with a reduction in the basic reproduction number of SARS-CoV-2 from 1.7 to 1.1, which was sufficient to avoid hospital saturation. We estimate that thanks to the young demographics, the risk of hospitalisation following infection was 0.3 times that of metropolitan France and that about 20% of the population was infected by July. Our model projections are consistent with a recent seroprevalence study. The study showcases how mathematical modelling can be used to support healthcare planning in a context of high uncertainty.

Estimating the burden of SARS-CoV-2 in France.

France has been heavily affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic and went into lockdown on 17 March 2020. Using models applied to hospital and death data, we estimate the impact of the lockdown and current population immunity. We find that 2.9% of infected individuals are hospitalized and 0.5% of those infected die (95% credible interval: 0.3 to 0.9%), ranging from 0.001% in those under 20 years of age to 8.3% in those 80 years of age or older. Across all ages, men are more likely to be hospitalized, enter intensive care, and die than women. The lockdown reduced the reproductive number from 2.90 to 0.67 (77% reduction). By 11 May 2020, when interventions are scheduled to be eased, we project that 3.5 million people (range: 2.1 million to 6.0 million), or 5.3% of the population (range: 3.3 to 9.3%), will have been infected. Population immunity appears to be insufficient to avoid a second wave if all control measures are released at the end of the lockdown.