Genomic assessment of invasion dynamics of SARS-CoV-2 Omicron BA.1.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) now arise in the context of heterogeneous human connectivity and population immunity. Through a large-scale phylodynamic analysis of 115,622 Omicron BA.1 genomes, we identified >6,000 introductions of the antigenically distinct VOC into England and analyzed their local transmission and dispersal history. We find that six of the eight largest English Omicron lineages were already transmitting when Omicron was first reported in southern Africa (22 November 2021). Multiple datasets show that importation of Omicron continued despite subsequent restrictions on travel from southern Africa as a result of export from well-connected secondary locations. Initiation and dispersal of Omicron transmission lineages in England was a two-stage process that can be explained by models of the country's human geography and hierarchical travel network. Our results enable a comparison of the processes that drive the invasion of Omicron and other VOCs across multiple spatial scales.

Managing sources of error during pandemics.

The COVID-19 pandemic has highlighted important considerations for modeling future pandemics.

Modelling the end of a Zero-COVID strategy using nirmatrelvir/ritonavir, vaccination and NPIs in Wallis and Futuna.

Background: Ending Zero-COVID is challenging, particularly when vaccine coverage is low. Considering Wallis and Futuna, a French Zero-COVID territory affected by reluctance to vaccination, low immunity and high levels of comorbidities, we investigate how targeted use of nirmatrelvir/ritonavir (brand name Paxlovid) can complement vaccination and non-pharmaceutical interventions (NPIs), and mitigate the epidemic rebound expected when Zero-COVID ends. Methods: We developed a discrete age-stratified compartmental model describing SARS-CoV-2 spread and healthcare impact once Wallis and Futuna reopens. It accounts for comorbidity risk groups (CRG), vaccine coverage (2 doses, 3 doses), the effectiveness of vaccines (recent or old injection), treatments and NPIs. In our baseline scenario, cases aged 65+ in intermediate/high CRG and 40+ in high CRG are eligible for treatment. Findings: The epidemic is expected to start 13-20 days after reopening with a doubling time of 1.6-3.7 days. For medium transmission intensity (R0 = 5), 134 (115-156) hospital admissions are expected within 3 months, with no pharmaceutical measures. In our baseline scenario, admissions are reduced by 11%-21% if 50% of the target group receive treatment, with maximum impact when combined with NPIs and vaccination. The number of hospitalisations averted (HA) per patient treated (PT) is maximum when 65+ in high CRG are targeted (0.124 HA/PT), quickly followed by 65+ in intermediate/high CRG (0.097 HA/PT), and any 65+ (0.093 HA/PT). Expanding the target group increases both PT and HA, but marginal gains diminish. Interpretation: Modelling suggests that test and treat may contribute to the mitigation of epidemic rebounds at the end of Zero-COVID, particularly in populations with low immunity and high levels of comorbidities. Funding: RECOVER, VEO, AXA, Groupama, SpF, IBEID, INCEPTION, EMERGEN.

Early chains of transmission of COVID-19 in France, January to March 2020.

IntroductionSARS-CoV-2, the virus that causes COVID-19, has spread rapidly worldwide. In January 2020, a surveillance system was implemented in France for early detection of cases and their contacts to help limit secondary transmissions.AimTo use contact-tracing data collected during the initial phase of the COVID-19 pandemic to better characterise SARS-CoV-2 transmission.MethodsWe analysed data collected during contact tracing and retrospective epidemiological investigations in France from 24 January to 30 March 2020. We assessed the secondary clinical attack rate and characterised the risk of a contact becoming a case. We described chains of transmission and estimated key parameters of spread.ResultsDuring the study period, 6,082 contacts of 735 confirmed cases were traced. The overall secondary clinical attack rate was 4.1% (95% confidence interval (CI): 3.6-4.6), increasing with age of index case and contact. Compared with co-workers/friends, family contacts were at higher risk of becoming cases (adjusted odds ratio (AOR): 2.1, 95% CI: 1.4-3.0) and nosocomial contacts were at lower risk (AOR: 0.3, 95% CI: 0.1-0.7). Of 328 infector/infectee pairs, 49% were family members. The distribution of secondary cases was highly over-dispersed: 80% of secondary cases were caused by 10% of cases. The mean serial interval was 5.1 days (interquartile range (IQR): 2-8 days) in contact tracing pairs, where late transmission events may be censored, and 6.8 (3-8) days in pairs investigated retrospectively.ConclusionThis study increases knowledge of SARS-CoV-2 transmission, including the importance of superspreading events during the onset of the pandemic.

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.

Epidemiology and control of SARS-CoV-2 epidemics in partially vaccinated populations: a modeling study applied to France.

BACKGROUND: Vaccination is expected to change the epidemiology and management of SARS-CoV-2 epidemics. METHODS: We used an age-stratified compartmental model calibrated to French data to anticipate these changes and determine implications for the control of an autumn epidemic. We assumed vaccines reduce the risk of hospitalization, infection, and transmission if infected by 95%, 60%, and 50%, respectively. RESULTS: In our baseline scenario characterized by basic reproduction number R0=5 and a vaccine coverage of 70-80-90% among 12-17, 18-59, and ≥ 60 years old, important stress on healthcare is expected in the absence of measures. Unvaccinated adults ≥60 years old represent 3% of the population but 43% of hospitalizations. Given limited vaccine coverage, children aged 0-17 years old represent a third of infections and are responsible for almost half of transmissions. Unvaccinated individuals have a disproportionate contribution to transmission so that measures targeting them may help maximize epidemic control while minimizing costs for society compared to non-targeted approaches. Of all the interventions considered including repeated testing and non-pharmaceutical measures, vaccination of the unvaccinated is the most effective. CONCLUSIONS: With the Delta variant, vaccinated individuals are well protected against hospitalization but remain at risk of infection and should therefore apply protective behaviors (e.g., mask-wearing). Targeting non-vaccinated individuals may maximize epidemic control while minimizing costs for society. Vaccinating children protects them from the deleterious effects of non-pharmaceutical measures. Control strategies should account for the changing SARS-CoV-2 epidemiology.

Lockdown impact on age-specific contact patterns and behaviours, France, April 2020.

BackgroundMany countries implemented national lockdowns to contain the rapid spread of SARS-CoV-2 and avoid overburdening healthcare capacity.AimWe aimed to quantify how the French lockdown impacted population mixing, contact patterns and behaviours.MethodsWe conducted an online survey using convenience sampling and collected information from participants aged 18 years and older between 10 April and 28 April 2020.ResultAmong the 42,036 survey participants, 72% normally worked outside their home, and of these, 68% changed to telework during lockdown and 17% reported being unemployed during lockdown. A decrease in public transport use was reported from 37% to 2%. Participants reported increased frequency of hand washing and changes in greeting behaviour. Wearing masks in public was generally limited. A total of 138,934 contacts were reported, with an average of 3.3 contacts per individual per day; 1.7 in the participants aged 65 years and older compared with 3.6 for younger age groups. This represented a 70% reduction compared with previous surveys, consistent with SARS-CoV2 transmission reduction measured during the lockdown. For those who maintained a professional activity outside home, the frequency of contacts at work dropped by 79%.ConclusionThe lockdown affected the population's behaviour, work, risk perception and contact patterns. The frequency and heterogeneity of contacts, both of which are critical factors in determining how viruses spread, were affected. Such surveys are essential to evaluate the impact of lockdowns more accurately and anticipate epidemic dynamics in these conditions.

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.

Early assessment of diffusion and possible expansion of SARS-CoV-2 Lineage 20I/501Y.V1 (B.1.1.7, variant of concern 202012/01) in France, January to March 2021.

The emergence of SARS-CoV-2 variant 20I/501Y.V1 (VOC-202012/1 or GR/501Y.V1) is concerning given its increased transmissibility. We reanalysed 11,916 PCR-positive tests (41% of all positive tests) performed on 7-8 January 2021 in France. The prevalence of 20I/501Y.V1 was 3.3% among positive tests nationwide and 6.9% in the Paris region. Analysing the recent rise in the prevalence of 20I/501Y.V1, we estimate that, in the French context, 20I/501Y.V1 is 52-69% more transmissible than the previously circulating lineages, depending on modelling assumptions.

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.

Impact of mass testing during an epidemic rebound of SARS-CoV-2: a modelling study using the example of France.

We used a mathematical model to evaluate the impact of mass testing in the control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Under optimistic assumptions, one round of mass testing may reduce daily infections by up to 20-30%. Consequently, very frequent testing would be required to control a quickly growing epidemic if other control measures were to be relaxed. Mass testing is most relevant when epidemic growth remains limited through a combination of interventions.

Heterogeneity in social and epidemiological factors determines the risk of measles outbreaks.

Political and environmental factors-e.g., regional conflicts and global warming-increase large-scale migrations, posing extraordinary societal challenges to policymakers of destination countries. A common concern is that such a massive arrival of people-often from a country with a disrupted healthcare system-can increase the risk of vaccine-preventable disease outbreaks like measles. We analyze human flows of 3.5 million (M) Syrian refugees in Turkey inferred from massive mobile-phone data to verify this concern. We use multilayer modeling of interdependent social and epidemic dynamics to demonstrate that the risk of disease reemergence in Turkey, the main host country, can be dramatically reduced by 75 to 90% when the mixing of Turkish and Syrian populations is high. Our results suggest that maximizing the dispersal of refugees in the recipient population contributes to impede the spread of sustained measles epidemics, rather than favoring it. Targeted vaccination campaigns and policies enhancing social integration of refugees are the most effective strategies to reduce epidemic risks for all citizens.

Household transmissions of SARS-CoV-2 in the time of unprecedented travel lockdown in China.

Importance: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in the city of Wuhan, China, in December 2019 and then spread globally. Limited information is available for characterizing epidemiological features and transmission patterns in the regions outside of Hubei Province. Detailed data on transmission at the individual level could be an asset to understand the transmission mechanisms and respective patterns in different settings. Objective: To reconstruct infection events and transmission clusters of SARS-CoV-2 for estimating epidemiological characteristics at household and non-household settings, including super-spreading events, serial intervals, age- and gender-stratified risks of infection in China outside of Hubei Province. Design Setting and Participants: 9,120 confirmed cases reported online by 264 Chinese urban Health Commissions in 27 provinces from January 20 to February 19, 2020. A line-list database is established with detailed information on demographic, social and epidemiological characteristics. The infection events are categorized into the household and non-household settings. Exposures: Confirmed cases of SARS-CoV-2 infections. Main Outcomes and Measures: Information about demographic characteristics, social relationships, travel history, timelines of potential exposure, symptom onset, confirmation, and hospitalization were extracted from online public reports. 1,407 infection events formed 643 transmission clusters were reconstructed. Results: In total 34 primary cases were identified as super spreaders, and 5 household super-spreading events were observed. The mean serial interval is estimated to be 4.95 days (standard deviation: 5.24 days) and 5.19 days (standard deviation: 5.28 days) for households and non-household transmissions, respectively. The risk of being infected outside of households is higher for age groups between 18 and 64 years, whereas the hazard of being infected within households is higher for age groups of young (<18) and elderly (>65) people. Conclusions and Relevance: The identification of super-spreading events, short serial intervals, and a higher risk of being infected outside of households for male people of age between 18 and 64 indicate a significant barrier to the case identification and management, which calls for intensive non-pharmaceutical interventions (e.g. cancellation of public gathering, limited access of public services) as the potential mitigation strategies.

Reconstruction of Transmission Pairs for Novel Coronavirus Disease 2019 (COVID-19) in Mainland China: Estimation of Superspreading Events, Serial Interval, and Hazard of Infection.

BACKGROUND: Knowledge on the epidemiological features and transmission patterns of novel coronavirus disease (COVID-19) is accumulating. Detailed line-list data with household settings can advance the understanding of COVID-19 transmission dynamics. METHODS: A unique database with detailed demographic characteristics, travel history, social relationships, and epidemiological timelines for 1407 transmission pairs that formed 643 transmission clusters in mainland China was reconstructed from 9120 COVID-19 confirmed cases reported during 15 January-29 February 2020. Statistical model fittings were used to identify the superspreading events and estimate serial interval distributions. Age- and sex-stratified hazards of infection were estimated for household vs nonhousehold transmissions. RESULTS: There were 34 primary cases identified as superspreaders, with 5 superspreading events occurred within households. Mean and standard deviation of serial intervals were estimated as 5.0 (95% credible interval [CrI], 4.4-5.5) days and 5.2 (95% CrI, 4.9-5.7) days for household transmissions and 5.2 (95% CrI, 4.6-5.8) and 5.3 (95% CrI, 4.9-5.7) days for nonhousehold transmissions, respectively. The hazard of being infected outside of households is higher for people aged 18-64 years, whereas hazard of being infected within households is higher for young and old people. CONCLUSIONS: Nonnegligible frequency of superspreading events, short serial intervals, and a higher risk of being infected outside of households for male people of working age indicate a significant barrier to the identification and management of COVID-19 cases, which requires enhanced nonpharmaceutical interventions to mitigate this pandemic.

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.