Drivers and impact of the early silent invasion of SARS-CoV-2 Alpha (preprint)

SARS-CoV-2 variants of concern (VOCs) circulated cryptically before being identified as a threat, delaying interventions. Understanding the drivers of such silent spread and its epidemic impact is critical to inform future response planning. Here, we integrated spatio-temporal records of international mobility, local epidemic growth and genomic surveillance into a Bayesian framework to reconstruct the early dissemination of Alpha out of the UK in the first three months after emergence. We found that silent circulation lasted from days to months and was logarithmically associated with sequencing coverage. Social restrictions in certain countries likely slowed down the seeding of local transmission by weeks, mitigating the negative consequences of late detection. Revisiting the initial spread of Alpha supports local mitigation at the destination in case of emerging events.

The importance of increasing primary vaccinationsagainst COVID-19 in Europe (preprint)

In the European Union, mass vaccination against COVID-19 staved off the strict restrictions that had characterized early epidemic response. Now, vaccination campaigns are focusing on booster doses, and primary vaccinations have all but halted. Still, 52 million European adults are unvaccinated. We investigated if reaching the still unvaccinated population in future vaccination campaigns would substantially decrease the current burden of COVID-19, which is substantial. We focused on vaccination homophily, whereby those who are unvaccinated are mostly in contact with other unvaccinated, making COVID-19 circulation easier. We quantified vaccination homophily and estimated its impact on COVID-19 circulation. We used an online survey of 1,055,286 people from 22 European countries during early 2022. We computed vaccination homophily as the association between reported vaccination status and perceived vaccination uptake among one's own social contacts, using a case-referent design and a hierarchical logistic model. We used this information in an analysis of the COVID-19 reproduction ratio to determine the impact of vaccine homophily in transmission. Vaccination homophily was present and strong everywhere: the average odds ratio of being vaccinated for a 10-percentage-point increase in coverage among contacts was 1.66 (95% CI=(1.60, 1.72)). Homophily was positively associated with the strictness of COVID-19-related restrictions in 2020 (Pearson=0.49, p-value=0.03). In the countries studied, 12%-to-18% of the reproduction ratio would be attributable to vaccine homophily. Reducing vaccination homophily may curb the reproduction ratio substantially even to the point of preventing recurrent epidemic waves. In addition to boosting those already vaccinated, increasing primary vaccination should remain a high priority in future vaccination campaigns, to reduce vaccination homophily: this combined strategy may decrease COVID-19 burden.

Global patterns and drivers of influenza decline during the COVID-19 pandemic (preprint)

Influenza circulation declined during the COVID-19 pandemic. The timing and extent of decline and its association with interventions against COVID-19 were described for some regions. Here, we provide a global analysis of the influenza decline between March 2020 and September 2021 and investigate its potential drivers. We computed influenza change by country and trimester relative to the 2014-2019 period using the number of samples in the FluNet database. We used random forests to determine important predictors in a list of 20 covariates including demography, weather, pandemic preparedness, COVID-19 incidence, and COVID-19 pandemic response. With a regression tree we then classified observations according to these predictors. We found that influenza circulation decreased globally, with COVID-19 incidence and pandemic preparedness being the two most important predictors of this decrease. The regression tree showed interpretable groups of observations by country and trimester: Europe and North America clustered together in spring 2020, with limited influenza decline despite strong COVID-19 restrictions; in the period afterwards countries of temperate regions, with high pandemic preparedness, high COVID-19 incidence and stringent social restrictions grouped together having strong influenza decline. Conversely, countries in the tropics, with altogether low pandemic preparedness, low reported COVID-19 incidence and low strength of COVID-19 response showed low influenza decline overall. A final group singled out four "zero-Covid" countries, with the lowest residual influenza levels. The spatiotemporal decline of influenza during the COVID-19 pandemic was global, yet heterogeneous. The sociodemographic context and stage of the COVID-19 pandemic showed non-linear associations with this decline. Zero-Covid countries maintained the lowest levels of reduction with strict border controls and despite close-to-normal social activity. These results suggest that the resurgence of influenza could take equally diverse paths. It also emphasizes the importance of influenza reseeding in driving countries' seasonal influenza epidemics.

Sanitary safety of the 2021 French Intensive Care Society medical conference: a case/control study

BackgroundIn-person mass gathering events (MGE) are returning after a period of restrictions, yet few prospective scientific evaluations of their safety are available.MethodsProspective observational study, including both attendees of the French Intensive Care Society (FICS) annual meeting held in Paris between June the 9th and June the 11th, 2021 and matched controls (healthcare professionals who stayed in the ICU during the conference). SARS-CoV-2 lateral flow test was performed on day 7. Follow-up occurred until day 21.ResultsOut of the 1824 healthcare professionals attending the congress (all of which fulfilled legal requirements: 7 days or more following a second dose of vaccine or a negative PCR test performed within less than 72 h), 520 (28.5%) agreed to participate. Follow-up data were received for 216 (41.5%) out of the 520 included attendees, and for 191 matched controls. No positive SARS-CoV-2 lateral flow test was reported in the attendees or in the matched controls. The probability of SARS-CoV-2 infection during the MGE was less than 1.7% in the attendees (95% confidence interval [0;1.7%]), less than 2% in the controls (95%CI [0;2%]) and the difference in probabilities of infection was less than 1.9% (95% CI [0;1.9%]).ConclusionDuring a low incidence period, in this population of congress attendees screened for SARS-CoV-2 by a lateral flow test at day 7, no positive cases could be documented, no concomitant infection occurred in the matched controls;suggesting no extra risk of infection during the MGE.Trial Registration: ClinicalTrial.gov, #NCT04918160.

Reactive vaccination of workplaces and schools against COVID-19 (preprint)

As vaccination against COVID-19 stalls in some countries, increased accessibility and more adaptive approaches may be useful to keep the epidemic under control. Here we study the impact of reactive vaccination targeting schools and workplaces where cases have been detected, with an agent-based model accounting for COVID-19 natural history, vaccine characteristics, individuals' demography and behaviour and social distancing. We study epidemic scenarios ranging from sustained spread to flare-up of cases, and we consider reactive vaccination alone and in combination with mass vaccination. With the same number of doses, reactive vaccination reduces cases more than non-reactive approaches, but may require concentrating a high number of doses over a short time in case of sustained spread. In case of flare-ups, quick implementation of reactive vaccination supported by enhanced test-trace-isolate practices would limit further spread. These results provide key information to promote an adaptive vaccination plan in the months to come.

Adherence and sustainability of interventions informing optimal control against COVID-19 pandemic (preprint)

After one year of stop-and-go COVID-19 mitigation, some European countries still experience sustained viral circulation due to the B.1.1.7 variant. As the prospect of phasing out this stage through vaccination draws closer, it is critical to balance the efficacy of long-lasting interventions and their impact on the quality of life. Focusing on the current situation in France, we show that moderate interventions require a much longer time to achieve the same result as high intensity lockdowns, with the additional risk of deteriorating control as adherence wanes. Integrating intensity and duration of social distancing in a data-driven "distress" index, we show that shorter strict lockdowns are largely more performant than longer moderate lockdowns, for similar intermediate distress and infringement on individual freedom. Our study shows that favoring milder interventions over more stringent short approaches on the basis of perceived acceptability could be detrimental in the long term, especially with waning adherence.

Risk of COVID-19 variant importation - How useful are travel control measures? (preprint)

We consider models for the importation of a new variant COVID-19 strain in a location already seeing propagation of a resident variant. By distinguishing contaminations generated by imported cases from those originating in the community, we are able to evaluate the contribution of importations to the dynamics of the disease in a community. We find that after an initial seeding, the role of importations becomes marginal compared to that of community-based propagation. We also evaluate the role of two travel control measures, quarantine and travel interruptions. We conclude that quarantine is an efficacious way of lowering importation rates, while travel interruptions have the potential to delay the consequences of importations but need to be applied within a very tight time window following the initial emergence of the variant.

Lockdown impact on age-specific contact patterns and behaviours in France (preprint)

In the first trimester 2020, a significant number of countries implemented general lockdowns of their populations to contain the quickly expanding SARS-CoV-2 epidemic and avoid major saturation of health care capacity. Understanding how these unprecedented measures impacted population behaviour and contact patterns is key to predict more accurately the health, social and economic impacts of such extreme actions if they were to be applied to future outbreaks. We set up an online survey to measure how the lockdown affected social contact patterns in France, and collected information from 42,036 participants aged 18 years and over between April 10 and April 28, 2020. Among the participants who normally worked outside home prior to the lockdown (72% of the survey population), 68% reported that they had moved to working from home and 17% reported being unemployed during the lockdown. Only 2% of participants used public transport during lockdown, as opposed to 37% before it. Participants reported increased frequency of washing hands, switch in greeting behaviour, but generally limited use of masks outside home. 138,934 contacts were reported, with an average 3.3 contacts per individual per day (1.7 for individuals aged >65 years old compared to 3.6 for younger age-groups). This represented a 70% reduction compared with previous surveys, consistent with reductions in transmission rates measured during the lockdown. Contacts in workplaces, shops, and transports on the previous day were respectively reported in only 11%, 31% and 0.5% of the participants. For those who maintained a professional activity outside home, the frequency of contacts at work dropped by 79%. This study shows that the lockdown dramatically affected population's behavior, work, risk perception and contact patterns. Both frequency and heterogeneity of contacts were affected, impacting potential important features of virus dissemination. Such surveys are essential to evaluate more accurately the impact of past or future lockdowns and anticipate epidemic dynamics in these conditions.

Underdetection of COVID-19 cases in France in the exit phase following lockdown (preprint)

A novel testing policy was implemented in May in France to systematically screen potential COVID-19 infections and suppress local outbreaks while lifting lockdown restrictions. 20,736 virologically-confirmed cases were reported in mainland France from May 13, 2020 (week 20, end of lockdown) to June 28 (week 26). Accounting for missing data and the delay from symptom onset to confirmation test, this corresponds to 7,258 [95% CI 7,160-7,336] cases with symptom onset during this period, a likely underestimation of the real number. Using age-stratified transmission models parameterized to behavioral data and calibrated to regional hospital admissions, we estimated that 69,115 [58,072-77,449] COVID-19 symptomatic cases occurred, suggesting that 9 out of 10 cases with symptoms were not ascertained. Median detection rate increased from 7% [6-9]% to 31% [28-35]% over time, with regional estimates varying from 11% (Grand Est) to 78% (Normandy) by the end of June. Healthcare-seeking behavior in COVID-19 suspect cases remained low (31%) throughout the period. Model projections for the incidence of symptomatic cases (4.5 [3.9-5.0] per 100,000) were compatible with estimates integrating participatory and virological surveillance data, assuming all suspect cases consulted. Encouraging healthcare-seeking behavior and awareness in suspect cases is critical to improve detection. Substantially more aggressive and efficient testing with easier access is required to act as a pandemic-fighting tool. These elements should be considered in light of the currently observed resurgence of cases in France and other European countries.

Emergency calls are early indicators of ICU bed requirement during the COVID-19 epidemic A retrospective study in Ile-de-France region, France (preprint)

Background: The aim of our retrospective study was to evaluate the earliest COVID19-related signal to anticipate requirements of intensive care unit (ICU) beds. Although the number of ICU beds is crucial during the COVID-19 epidemic, there is no recognized early indicator to anticipate it. Methods: In the Ile-de-France region, from February 20 to May 5, 2020, emergency medical service (EMS) calls and the response provided (ambulances) together the percentage of positive reverse transcriptase polymerase chain reaction (RT-PCR) tests, general practitioner (GP) and emergency department (ED) visits, and hospital admissions of COVID-19 patients were recorded daily and compared to the number of ICU patients. Correlation curve analysis was performed to determine the best correlation coefficient, depending on the number of days the indicator has been shifted. Primary endpoint was the number of ICU patients. Results: EMS calls, percentage of positive RT-PCR tests, ambulances used, ED and GP visits of COVID-19 patients were strongly associated with COVID-19 ICU patients with an anticipation delay of 23, 15, 14, 13, and 12 days respectively. Hospitalization did not anticipate ICU bed requirement. Conclusion: The daily number of COVID19-related telephone calls received by the EMS and corresponding dispatch ambulances, and the proportion of positive RT-PCR tests were the earliest indicators of the number of COVID19 patients requiring ICU care during the epidemic crisis, rapidly followed by ED and GP visits. This information may help health authorities to anticipate a future epidemic, including a second wave of COVID19 or decide additional social measures.

Anatomy of digital contact tracing: role of age, transmission setting, adoption and case detection (preprint)

The efficacy of digital contact tracing against COVID-19 epidemic is debated: smartphone penetration is limited in many countries, non-uniform across age groups, with low coverage among elderly, the most vulnerable to SARS-CoV-2. We developed an agent-based model to precise the impact of digital contact tracing and household isolation on COVID-19 transmission. The model, calibrated on French population, integrates demographic, contact-survey and epidemiological information to describe the risk factors for exposure and transmission of COVID-19. We explored realistic levels of case detection, app adoption, population immunity and transmissibility. Assuming a reproductive ratio R = 2.6 and 50% detection of clinical cases, a ~20% app adoption reduces peak incidence by ~35%. With R = 1.7, >30% app adoption lowers the epidemic to manageable levels. Higher coverage among adults, playing a central role in COVID-19 transmission, yields an indirect benefit for elderly. These results may inform the inclusion of digital contact tracing within a COVID-19 response plan.

Expected impact of reopening schools after lockdown on COVID-19 epidemic in Ile-de-France (preprint)

As several countries around the world are planning exit strategies to progressively lift the rigid social restrictions implemented with lockdown, different options are being chosen regarding the closure or reopening of schools. We evaluate the expected impact of reopening schools in lIe-de-France region after the withdrawal of lockdown currently scheduled for May 11, 2020. We explore several scenarios of partial, progressive, or full school reopening, coupled with moderate social distancing interventions and large-scale tracing, testing, and isolation. Accounting for current uncertainty on the role of children in COVID-19 epidemic, we test different hypotheses on children's transmissibility distinguishing between younger children (pre-school and primary school age) and adolescents (middle and high school age). Reopening schools after lifting lockdown will likely lead to an increase in the number of COVID-19 cases in the following 2 months, even with lower transmissibility of children, yet protocols exist that would allow maintaining the epidemic under control without saturating the healthcare system. With pre-schools and primary schools in session starting May 11, ICU occupation would reach at most 72% [55,83]% (95% probability ranges) of a 1,500-bed capacity (here foreseen as the routine capacity restored in the region post-first wave) if no other school level reopens before summer or if middle and high schools reopen one month later through a progressive protocol (increasing attendance week by week). Full attendance of adolescents at school starting in June would overwhelm the ICU system (138% [118,159]% occupation). Reopening all schools on May 11 would likely lead to a second wave similar to the one recently experienced, except if maximum attendance is limited to 50% for both younger children and adolescents. Based on the estimated situation on May 11, no substantial difference in the epidemic risk is predicted between progressive and prompt reopening of pre-schools and primary schools, thus allowing full attendance of younger children mostly in need of resuming learning and development. Reopening would require however large-scale trace and testing to promptly isolate cases, in addition to moderate social distancing interventions. Full attendance in middle and high schools is instead not recommended. Findings are consistent across different assumptions on the relative transmissibility of younger children and for small increase of the reproductive number possibly due to decreasing compliance to lockdown.

Estimating the burden of SARS-CoV-2 in France (preprint)

France has been heavily affected by the SARS-CoV-2 epidemic and went into lockdown on the 17th March 2020. Using models applied to hospital and death data, we estimate the impact of the lockdown and current population immunity. We find 2.6% of infected individuals are hospitalized and 0.53% die, ranging from 0.001% in those <20y to 8.3% in those >80y. Across all ages, men are more likely to be hospitalized, enter intensive care, and die than women. The lockdown reduced the reproductive number from 3.3 to 0.5 (84% reduction). By 11 May, when interventions are scheduled to be eased, we project 3.7 million (range: 2.3-6.7) people, 5.7% of the population, will have been infected. Population immunity appears insufficient to avoid a second wave if all control measures are released at the end of the lockdown.

Expected impact of lockdown in Ile-de-France and possible exit strategies (preprint)

BackgroundMore than half of the global population is under strict forms of social distancing. Estimating the expected impact of lockdown and exit strategies is critical to inform decision makers on the management of the COVID-19 health crisis. MethodsWe use a stochastic age-structured transmission model integrating data on age profile and social contacts in Ile-de-France to (i) assess the epidemic in the region, (ii) evaluate the impact of lockdown, and (iii) propose possible exit strategies and estimate their effectiveness. The model is calibrated to hospital admission data before lockdown. Interventions are modeled by reconstructing the associated changes in the contact matrices and informed by mobility reductions during lockdown evaluated from mobile phone data. Different types and durations of social distancing are simulated, including progressive and targeted strategies, with large-scale testing. ResultsWe estimate the reproductive number at 3.18 [3.09, 3.24] (95% confidence interval) prior to lockdown and at 0.68 [0.66, 0.69] during lockdown, thanks to an 81% reduction of the average number of contacts. Model predictions capture the disease dynamics during lockdown, showing the epidemic curve reaching ICU system capacity, largely strengthened during the emergency, and slowly decreasing. Results suggest that physical contacts outside households were largely avoided during lockdown. Lifting the lockdown with no exit strategy would lead to a second wave overwhelming the healthcare system, if conditions return to normal. Extensive case-finding and isolation are required for social distancing strategies to gradually relax lockdown constraints. ConclusionsAs France experiences the first wave of COVID-19 pandemic in lockdown, intensive forms of social distancing are required in the upcoming months due to the currently low population immunity. Extensive case-finding and isolation would allow the partial release of the socio-economic pressure caused by extreme measures, while avoiding healthcare demand exceeding capacity. Response planning needs to urgently prioritize the logistics and capacity for these interventions.

Excess cases of Influenza like illnesses in France synchronous with COVID19 invasion. (preprint)

Several French regions where COVID19 has been reported currently show a renewed increase in ILI cases in the general practice based Sentinelles network. Here we computed the number of excess cases by region and found correlation with the number of reported COVID19 cases so far. These data suggest larger circulation of SARS-CoV-2 in the French population than apparent from confirmed cases.

Lessons learnt from 288 COVID-19 international cases: importations over time, effect of interventions, underdetection of imported cases (preprint)

288 cases have been confirmed out of China from January 3 to February 13, 2020. We collected and synthesized all available information on these cases from official sources and media. We analyzed importations that were successfully isolated and those leading to onward transmission. We modeled their number over time, in relation to the origin of travel (Hubei province, other Chinese provinces, other countries) and interventions. We characterized importations timeline to assess the rapidity of isolation, and epidemiologically linked clusters to estimate the rate of detection. We found a rapid exponential growth of importations from Hubei, combined with a slower growth from the other areas. We predicted a rebound of importations from South East Asia in the upcoming weeks. Time from travel to detection has considerably decreased since the first importation, however 6 cases out of 10 were estimated to go undetected. Countries outside China should be prepared for the possible emergence of several undetected clusters of chains of local transmissions.

Preparedness and vulnerability of African countries against introductions of 2019-nCoV (preprint)

The novel coronavirus (2019-nCoV) epidemic has spread to 23 countries from China. Local cycles of transmission already occurred in 7 countries following case importation. No African country has reported cases yet. The management and control of 2019-nCoV introductions heavily relies on the public health capacity of a country. Here we evaluate the preparedness and vulnerability of African countries against their risk of importation of 2019-nCoV. We used data on air travel volumes departing from airports in the infected provinces in China and directed to Africa to estimate the risk of introduction per country. We determined the countries capacity to detect and respond to cases with two indicators: preparedness, using the WHO International Health Regulation Monitoring and Evaluation Framework; and vulnerability, with the Infectious Disease Vulnerability Index. Countries were clustered according to the Chinese regions contributing the most to their risk. Findings: Countries at the highest importation risk (Egypt, Algeria, Republic of South Africa) have moderate to high capacity to respond to outbreaks. Countries at moderate risk (Nigeria, Ethiopia, Sudan, Angola, Tanzania, Ghana, Kenya) have variable capacity and high vulnerability. Three clusters of countries are identified that share the same exposure to the risk originating from the provinces of Guangdong, Fujian, and Beijing, respectively. Interpretation: Several countries in Africa are stepping up their preparedness to detect and cope with 2019-nCoV importations. Resources and intensified surveillance and capacity capacity should be urgently prioritized towards countries at moderate risk that may be ill-prepared to face the importation and to limit onward transmission.