Background
More than half of the global population is under strict forms of social distancing [
1,
2], with more than 90 countries in lockdown to fight against COVID-19 pandemic. France implemented the lockdown from March 17 to May 11, 2020 [
3]. The aim of this measure is to drastically increase the so-called social distance between individuals to break the chains of transmission and reduce COVID-19 spread. It is an unprecedented measure that was previously implemented only in Italy, Spain, and Austria [
2], following the example of China [
4], to curb the dramatic increase of hospitalizations and admissions to ICU approaching saturation of the healthcare system.
The implementation of extreme measures of social distancing, including mobility restrictions, banning of mass gatherings, closure of schools and work activities, isolation, and quarantine, helped control the first wave of COVID-19 pandemic in China [
4‐
8]. Such exceptional coverage and intensive degree of intervention coupled with strict enforcement may be key to the resulting outcome. How this will play out in Europe is still uncertain [
9,
10]. Most importantly, how to relax such stringent constraints on social life and economy while controlling the health crisis remains under investigation [
11‐
13].
Here we use an age-structured mathematical model to (i) assess the current COVID-19 pandemic situation in France, (ii) evaluate the impact of the lockdown implemented nationwide on March 17, 2020, and (iii) estimate the effectiveness of possible exit strategies. The model is applied to the region of Île-de-France (heavily affected by the epidemic); it is data-driven and calibrated on hospital admission data for the region prior to lockdown. Different types and durations of social distancing interventions are explored, including a progressive lifting of the lockdown targeted on specific classes of individuals (e.g., allowing a larger portion of the population to go to work, while protecting the elderly) and large-scale testing for case finding and isolation. The aim is to identify possible strategies to reduce the public health impact following the lifting of the lockdown.
The original version of this study was made available as a preprint in mid-April, 1 month before the exit from lockdown. This revised version updates the comparison and validation of model projections, once data became available, while maintaining the context of the beginning of lockdown.
Discussion
We use a stochastic age-structured epidemic transmission model calibrated on hospital admission data in Île-de-France to evaluate the impact of lockdown and exit strategies in controlling COVID-19 epidemic in the region. Our estimate of the reproductive number prior to lockdown is in line with estimates for the epidemic growth in Europe prior to the implementation of interventions [
9,
10], with results from a meta-analysis of the literature [
12,
45], and with concurrent studies in France [
35,
48]. We predict it decreased significantly during lockdown with a 95% probability range well below 1. Under these conditions, the occupancy of the ICU system reaches a plateau before clearly showing a decreasing tendency after several weeks of lockdown, as also observed in other countries [
18]. As of May 11, the model predicts a 48% of ICU occupancy, with less than 30 new admissions to ICUs per day.
Lifting lockdown with no exit strategy in place, i.e., going back to pre-lockdown conditions, would inevitably lead to large rebound effects, as the immunity of the population is estimated to be still very low (from 2 to 13% considering both values of probability of being asymptomatic explored), in agreement with other estimates [
9,
35]. Prolonged interventions of moderate to high intensity could additionally delay the epidemic peak by at least 2 months compared to the no-exit strategy and reduce its peak incidence by more than 80%, but would not avoid exceeding ICU capacity (peak demand of 2–15 times the restored ICU capacity of the region). Even with a 100% increase of ICU capacity to face the second peak, strict interventions would be required for the next full year.
Control of the epidemic without overwhelming the healthcare system requires coupling social distancing measures with aggressive testing to promptly identify infectious individuals and isolate them. Response capacity is critical to lift the lockdown, so that the timeline of these interventions should be carefully planned based on achieved preparedness. We consider different levels of testing capacity starting from the month of May or June. If case isolation is performed on average 1.5 day after infection and is efficient (90% reduction of contacts), we find that identifying at least 50% of all new cases would be required to rapidly reduce the burden on the healthcare system while exiting lockdown. Lower tracing capacity starting May would need to be coupled with more vigorous social distancing to keep the epidemic under control. To release constraints on the population while building capacity, a longer lockdown till June would aid releasing the pressure on the healthcare system. Also, it would be ideal to perform contact tracing and testing while the epidemic is at low activity levels. The benefit of these measures would go beyond the epidemic mitigation and extend to revising and optimizing protocols to improve case finding and isolation—compared to the first phase of the epidemic—under more controlled conditions (reduced mixing of the population).
Fast, efficient, and large-scale contact tracing [
31] is one essential component allowing the partial release of social distancing constraints in the upcoming months. This would require digital technologies that are currently being investigated in Europe [
49] following the examples of COVID-19 response of countries in Asia [
50]. Logistical constraints need to be envisioned, including large-scale and rapid diagnostic capacity, large-scale adoption of the contact tracing technology by the population [
51], uptake of recommendations, and coordination across countries to allow contact tracing across borders [
49].
The set of mild or moderate interventions considered here still impose limitations. We tested strategies allowing a larger proportion of the population to go back to work, also to partially release the huge economic pressure that lockdown generated. Global economic uncertainty is at a record high [
52], due to the fear of COVID-19 pandemic spread, income losses, and globally stalled economies because of exceptional interventions freezing production. As a side effect, lockdown has likely created a forced opportunity to re-organize certain professional activities to make telework possible and efficient at larger scale than previously foreseen. Prior to lockdown, a small fraction of Europeans practiced telework [
37]. If this change of paradigm is maintained beyond emergency response, it would be extremely valuable in the medium- to long-term to aid the control of the epidemic below healthcare system saturation. Rotation of individuals working from home (e.g., every week, or every 2 weeks) can be envisioned to maintain the required social distancing levels in the community while ensuring real-life connections.
Here we consider unchanged intervention measures regarding children and seniors across all scenarios. Schools are assumed to remain closed, though reopening of certain school levels is possible under different protocols of attendance [
44]. Seniors are considered to maintain a reduction of contacts through hygienic measures and physical distance, as they are especially vulnerable against COVID-19. Planning for the upcoming months under these conditions should include logistics to facilitate daily routines of the elderly beyond this phase of emergency, e.g., improving delivery of grocery and medicines, facilitating remote access to healthcare, providing learning programs for the use of technologies to stay connected, and other initiatives. Reopening of the schools in the fall/winter should be explored in the following months once the impact of these interventions will be further assessed [
44].
ICU capacity underwent a large increase in the last weeks to face the rapid surge of patients in critical conditions [
16]. Capacities have been stretched in the most affected regions, and patients have also been transferred to other regions for adequate care. Exiting the current emergency, we envision that ICU capacity will be restored to lower levels for the upcoming months. If a second emergency were to occur, the system would need to be strengthened again to higher limits.
Our findings are based on the mechanistically reconstructed changes in the contact matrices that aim to reproduce the implemented social distancing measures, as done in previous works [
7,
12]. While reconstructing changes in the contact matrices remains arbitrary, available elements support our estimates. First, not being fitted to the lockdown period, our contact matrices reconstructed from social contact data lead to model projections in line with observations across several indicators. The fit to the epidemic trajectory, retrospectively performed once data became available, shows that a correction of only 5% in the transmissibility per contact is needed to better describe the epidemic compared to our mechanistically reconstructed matrices. This indicates that the assumptions behind the reconstruction of the matrix, affecting each age bracket in a different way, are able to capture the dynamics of the epidemic during lockdown. Such finding can improve the parameterization of similar models based on contact matrices for the study of COVID-19 epidemic in other regions or countries. At the same time, it also suggests that physical contacts were successfully avoided during lockdown, in compliance with the recommendations of health authorities. Second, our predicted reduction of 81% of the average number of contacts during lockdown is lower than the one measured in China in the cities of Wuhan (86%) and Shanghai (89%) [
46]. Stricter measures were implemented in China during lockdown compared to Europe, including for example complete suspension of public transport, ban of cars from roads except for the essential services, barring residents from leaving the apartment in certain areas or limiting it to one household member few days per week, performing health checks door to door to identify and isolate ill individuals. These measures are expected therefore to have a more substantial effect on reducing the number of contacts per individual compared to social distancing measures implemented in many European countries. Indeed, under conditions measured in China, the ICU system is predicted by our model to receive less patients and clear them more rapidly than what we currently see in the data. Third, our prediction for contact reduction is close to, but larger than the empirically estimated 73% reduction of a recent social contact survey conducted in the UK during the lockdown phase [
45]. Implementation of social distancing however differs in the two countries. For example, in the UK, parks remain open, no self-declaration to circulate is needed, and displacements are not restricted on distance. Assuming the conditions measured in the UK, the model predicts a first peak exceeding ICU capacity. Collecting contact data in France during lockdown, as done in the UK, would allow a better measurement of the mixing patterns altered by social distancing to be compared with our synthetically reconstructed lockdown matrix. Possible changes in population adherence over time, and consequential strengthening of measures by authorities, need however to be taken into account.
Our study is affected by limitations. We did not include explicitly the effect of using masks. Evidence on seasonal coronaviruses indicates that surgical masks may reduce onward transmission [
53]. Masks are largely adopted or enforced in Asia, while they just became a recommended or compulsory protection in certain areas in Europe and the USA, mainly as a precautionary measure [
54]. If effective, their widespread use may help decrease the risk of transmission in the community. As more epidemiological evidence accrues, this effect can be taken into account and help further alleviate control measures. We did not consider seasonal behavior in viral transmission [
11,
13], because of current lack of evidence. In our simulated epidemics, multiple peaks are observed because of the implementation of social distancing interventions able to reduce the reproductive number below 1. If seasonal forcing is to be expected, the interplay with seasonality should be carefully considered in the planning of the short- and long-term control strategies [
11]. Exit strategies are based on matrices including both physical and non-physical contacts. We saw that excluding physical contacts substantially contributed to the reduction of the reproductive number during lockdown. At this stage, however, large uncertainty exists on recommendations and protocols imposed by authorities to phase out lockdown. Moreover, our scenarios plan out for several months, and recommendations as well as population adoption may strongly change over this long time period. Findings reported in the main text therefore correspond to a conservative choice. If physical contacts are avoided for several months, the epidemic would go locally extinct. Treatment of COVID-19 patients improved over time, as documented by lower probabilities for requiring intensive care and shorter durations in ICU (Additional file
1). These data became available at the time of revision and were not included in the analysis. The more efficient management of COVID-19 patients is expected to reduce the burden in the upcoming months.
We tested two values for the probability of being asymptomatic, as there still exists large uncertainty [
20‐
23]. Few studies investigated the clinical progression of symptoms over time until viral clearance. Additional household studies now launched in Europe will help providing a better understanding of the presence of asymptomatic cases and their contribution to transmission. Evidence so far seems to indicate that this fraction may be low [
23]; therefore, we presented in the main paper results for
pa= 0.2. Estimates of age-specific severity and case fatality rates are still rapidly evolving and often vary across countries due to different surveillance systems and testing protocols in place. Here we used estimates of age-specific severity informed from a model-based analysis on individual-level data from China and other countries [
19]. Rates describing the hospitalization duration and outcome of a patient were based on French data [
28]. Infection fatality ratios estimated by our model are consistent with estimates provided in Ref. [
19]. We do not consider here data on comorbidities that will alter hospitalization and fatality rates. Large-scale testing in France will allow us to robustly estimate age-specific hospitalization rates to better inform the model
.
Concurrently to our work, other studies became available that assessed the epidemic in France [
35,
48]. All studies independently produced similar estimates characterizing the epidemic and the effectiveness of lockdown, providing a consensus of evaluations despite modeling discrepancies (e.g., equal transmissibility across asymptomatic and symptomatic infectious individuals in Ref. [
35], or 90% reduction in transmissibility of asymptomatic cases in Ref. [
48], compared to our 45% reduction informed by prior modeling work [
8]). However, each focused on different aspects, specifically to evaluate the impact of lockdown and estimate population immunity [
35], or to estimate the total number of averted ICU admissions and deaths due to lockdown [
48], whereas no study proposed exit strategies and their evaluation while on lockdown.
Our results are based on data from Île-de-France, currently one of the most affected regions by the COVID-19 epidemic in the country, and not directly applicable to other regions. Few differences in the results due to variations of age profile across regions are to be expected [
55]. The most relevant changes will however result from the different epidemic phase experienced by each region at the moment of nationwide application of the lockdown. Overall, findings on exit strategies remain valid, but more specific interventions, differentially targeting the regions, may be envisioned.
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