The effect of variation of individual infectiousness on SARS-CoV-2 transmission in households

Quantifying variation of individual infectiousness is critical to inform disease control. Previous studies reported substantial heterogeneity in transmission of many infectious diseases (including SARS-CoV-2). However, those results are difficult to interpret since the number of contacts is rarely considered in such approaches. Here, we analyze data from 17 SARS-CoV-2 household transmission studies conducted in periods dominated by ancestral strains, in which the number of contacts was known. By fitting individual-based household transmission models to these data, accounting for number of contacts and baseline transmission probabilities, the pooled estimate suggests that the 20% most infectious cases have 3.1-fold (95% confidence interval: 2.2-4.2 fold) higher infectiousness than average cases, which is consistent with the observed heterogeneity in viral shedding. Household data can inform the estimation of transmission heterogeneity, which is important for epidemic management. One Sentence SummaryIn this study, variation of individual infectiousness is quantified. Potential sources of such variation, particularly heterogeneity of viral shedding is discussed.

Impact and mitigation of sampling bias to determine viral spread: evaluating discrete phylogeography through CTMC modeling and structured coalescent model approximations

Bayesian phylogeographic inference is a powerful tool in molecular epidemiological studies that enables reconstructing the origin and subsequent geographic spread of pathogens. Such inference is, however, potentially affected by geographic sampling bias. Here, we investigated the impact of sampling bias on the spatiotemporal reconstruction of viral epidemics using Bayesian discrete phylogeographic models and explored different operational strategies to mitigate this impact. We considered the continuous-time Markov chain (CTMC) model and two structured coalescent approximations (BASTA and MASCOT). For each approach, we compared the estimated and simulated spatiotemporal histories in biased and unbiased conditions based on simulated epidemics of rabies virus (RABV) in dogs in Morocco. While the reconstructed spatiotemporal histories were impacted by sampling bias for the three approaches, BASTA and MASCOT reconstructions were also biased when employing unbiased samples. Increasing the number of analyzed genomes led to more robust estimates at low sampling bias for CTMC. Alternative sampling strategies that maximize the spatiotemporal coverage greatly improved the inference at intermediate sampling bias for CTMC, and to a lesser extent, for BASTA and MASCOT. In contrast, allowing for time-varying population sizes in MASCOT resulted in robust inference. We further applied these approaches to two empirical datasets: a RABV dataset from the Philippines and a SARS-CoV-2 dataset describing its early spread across the world. In conclusion, sampling biases are ubiquitous in phylogeographic analyses but may be accommodated by increasing sample size, balancing spatial and temporal composition in the samples, and informing structured coalescent models with reliable case count data.

SARS-CoV-2 IgG seroprevalence surveys in blood donors before the vaccination campaign, France 2020-2021

We conducted a cross-sectional study for SARS-CoV-2 anti-S1 IgG prevalence in French blood donors (n=32605), from May-2020 to January-2021. A mathematical model combined seroprevalence with daily number of hospital admissions to estimate the probability of hospitalization upon infection and determine the number of infections while correcting for antibody decay. There was an overall seroprevalence increase over the study period and we estimate that [~]15% of the French population had been infected by SARS-CoV-2 by January-2021. The infection/hospitalization ratio increased with age, from 0.56% (18-30yo) to 6.75% (61-70yo). Half of the IgG-S1 positive individuals had no detectable antibodies 4 to 5 months after infection. The seroprevalence in group O donors (7.43%) was lower (p=0.003) than in A, B and AB donors (8.90%). We conclude, based on seroprevalence data and mathematical modelling, that the overall immunity in the French population before the vaccination campaign started was too low to achieve herd immunity.

Humoral Immunity to SARS-CoV-2 and Inferred Protection from Infection in a French Longitudinal Community Cohort

Population-level immunity to SARS-CoV-2 is growing through vaccination as well as ongoing circulation. Given waning immunity and emergence of new variants, it is important to dynamically determine the risk of re-infection in the population. For estimating immune protection, neutralization titers are most informative, but these assays are difficult to conduct at a population level. Measurement of antibody levels can be implemented at high throughput, but has not been robustly validated as a correlate of protection. Here, we have developed a method that predicts neutralization and protection based on variant-specific antibody measurements to SARS-CoV-2 antigens. This approach allowed us to estimate population-immunity in a longitudinal cohort from France followed for up to 2 years. Participants with a single vaccination or immunity caused by infection only are especially vulnerable to COVID-19 or hospitalization due to SARS-CoV-2. While the median reduced risk to COVID-19 in participants with 3 vaccinations was 96%, the median reduced risk among participants with infection-acquired immunity only was 42%. The results presented here are consistent with data from vaccine-effectiveness studies indicating robustness of our approach. Our multiplex serological assay can be readily optimized and employed to study any new variant and provides a framework for development of an assay that would include protection estimates.

Selection for infectivity profiles in slow and fast epidemics, and the rise of SARS-CoV-2 variants

Evaluating the characteristics of emerging SARS-CoV-2 variants of concern is essential to inform pandemic risk assessment. A variant may grow faster if it produces a larger number of secondary infections (transmissibility advantage) or if the timing of secondary infections (generation time) is better. So far, assessments have largely focused on deriving the transmissibility advantage assuming the generation time was unchanged. Yet, knowledge of both is needed to anticipate impact. Here we develop an analytical framework to investigate the contribution of both the transmissibility advantage and generation time to the growth advantage of a variant. We find that the growth advantage depends on the epidemiological context (level of epidemic control). More specifically, variants conferring earlier transmission are more strongly favoured when the historical strains have fast epidemic growth, while variants conferring later transmission are more strongly favoured when historical strains have slow or negative growth. We develop these conceptual insights into a statistical framework to infer both the transmissibility advantage and generation time of a variant. On simulated data, our framework correctly estimates both parameters when it covers time periods characterized by different epidemiological contexts. Applied to data for the Alpha and Delta variants in England and in Europe, we find that Alpha confers a +54% [95% CI, 45-63%] transmissibility advantage compared to previous strains, and Delta +140% [98-182%] compared to Alpha, and mean generation times are similar to historical strains for both variants. This work helps interpret variant frequency and will strengthen risk assessment for future variants of concern.

How well does SARS-CoV-2 spread in hospitals?

Covid-19 poses significant risk of nosocomial transmission, and preventing this requires good estimates of the basic reproduction number R0 in hospitals and care facilities, but these are currently lacking. Such estimates are challenging due to small population sizes in these facilities and inconsistent testing practices. We estimate the patient-to-patient R0 and daily transmission rate of SARS-CoV-2 using data from a closely monitored hospital outbreak in Paris 2020 during the first wave. We use a realistic epidemic model which accounts for progressive stages of infection, stochastic effects and a large proportion of asymptomatic infections. Innovatively, we explicitly include changes in testing capacity over time, as well as the evolving sensitivity of PCR testing at different stages of infection. We conduct rigorous statistical inference using iterative particle filtering to fit the model to the observed patient data and validate this methodology using simulation. We provide estimates for R0 across the entire hospital (2.6) and in individual wards (from 3 to 15), possibly reflecting heterogeneity in contact patterns or control measures. An obligatory mask-wearing policy introduced during the outbreak is likely to have changed the R0, and we estimate values before (8.7) and after (1.3) its introduction, corresponding to a policy efficacy of 85%.

Self-testing and vaccination against COVID-19 to minimize school closure

Schools were closed extensively in 2020-2021 to counter COVID-19 spread, impacting students education and well-being. With highly contagious variants expanding in Europe, safe options to maintain schools open are urgently needed. We developed an agent-based model of SARS-CoV-2 transmission in school. We used empirical contact data in a primary and a secondary school, and data from pilot screenings in 683 schools during the 2021 spring Alpha wave in France. We fitted the model to observed school prevalence to estimate the school-specific reproductive number and performed a cost-benefit analysis examining different intervention protocols. We estimated RAlpha=1.40 (95%CI 1.35-1.45) in the primary and RAlpha=1.46 (1.41-1.51) in the secondary school during the wave, higher than Rt estimated from community surveillance. Considering the Delta variant and vaccination coverage in Europe, we estimated RDelta=1.66 (1.60-1.71) and RDelta=1.10 (1.06-1.14) in the two settings, respectively. Under these conditions, weekly screening with 75% adherence would reduce cases by 34% (95%CI 32-36%) in the primary and 36% (35-39%) in the secondary school compared to symptom-based testing. Insufficient adherence was recorded in pilot screening (median [≤]53%). Regular screening would also reduce student-days lost up to 80% compared to reactive closure. Moderate vaccination coverage in students would still benefit from regular screening for additional control (23% case reduction with 50% vaccinated children). COVID-19 pandemic will likely continue to pose a risk for school opening. Extending vaccination coverage in students, complemented by regular testing largely incentivizing adherence, are essential steps to keep schools open, especially under the threat of more contagious variants.

Reactive vaccination of workplaces and schools against COVID-19

AbstractAs 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 are detected, with an agent-based model accounting for COVID-19 natural history, vaccine characteristics, individuals demography and behaviour and social distancing. At an equal number of doses reactive vaccination produces a higher reduction in cases compared with non-reactive strategies, in the majority of scenarios. However, at high initial vaccination coverage or low incidence, few people are found to vaccinate around cases, thus the reactive strategy may be less effective than non-reactive strategies with moderate/high vaccination pace. In case of flare-ups, reactive vaccination could hinder 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 deployment.

Impact of BNT162b2 vaccination and isolation on SARS-CoV-2 transmission in Israeli households: an observational study

BackgroundMassive vaccination rollouts against SARS-CoV-2 infections have facilitated the easing of control measures in countries like Israel. While several studies have characterized the effectiveness of vaccines against severe forms of COVID-19 or SARS-CoV-2 infection, estimates of their impact on transmissibility remain limited. Here, we evaluated the role of vaccination and isolation on SARS-CoV-2 transmission within Israeli households. MethodsFrom December 2020 to April 2021, confirmed cases were identified among healthcare workers of the Sheba Medical Centre and their family members. Households were recruited and followed up with repeated PCR for a minimum of ten days after case confirmation. Symptoms and vaccination information were collected at the end of follow-up. We developed a data augmentation Bayesian framework to ascertain how age, isolation and BNT162b2 vaccination with more than 7 days after the 2nd dose impacted household transmission of SARS-CoV-2. Findings210 households with 215 index cases were enrolled. 269 out of 687 (39%) household contacts developed a SARS-CoV-2 infection. Of those, 170 (63%) developed symptoms. Children below 12 years old were less susceptible than adults/teenagers (Relative Risk RR=0{middle dot}50, 95% Credible Interval CI 0{middle dot}32-0{middle dot}79). Vaccination reduced the risk of infection among adults/teenagers (RR=0{middle dot}19, 95% CI 0{middle dot}07-0{middle dot}40). Isolation reduced the risk of infection of unvaccinated adult/teenager (RR=0{middle dot}11, 95% CI 0{middle dot}05-0{middle dot}19) and child contacts (RR=0{middle dot}16, 95% CI 0{middle dot}07-0{middle dot}31) compared to unvaccinated adults/teenagers that did not isolate. Infectivity was significantly reduced in vaccinated cases (RR=0{middle dot}22, 95% CI 0{middle dot}06-0{middle dot}70). InterpretationWithin households, vaccination reduces both the risk of infection and of transmission if infected. When contacts were not vaccinated, isolation also led to important reductions in the risk of transmission. Vaccinated contacts might reduce their risk of infection if they isolate, although this requires confirmation with additional data. FundingSheba Medical Center. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe efficacy of vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmissions in households remains understudied. On June 28, 2021, we searched PubMed and medRxiv for articles published between December 1, 2020, and June 28, 2021, using the following combination of search terms: ("COVID-19" OR "SARS-CoV-2") AND ("household*" OR "famil*") AND "transmission" AND "vaccination". Our search yielded two articles that investigated the effect of vaccination on SARS-CoV-2 transmission in households. They showed a lower risk of infection in households with vaccinees. Vaccine efficacy on the risk of infection was estimated to 80% after the 2nd dose, and vaccine efficacy on the risk of transmission if infected was estimated to 49% 21 days after the 1st dose. However, these estimates are derived from surveillance data with no active follow-up of the households. In addition, the impact of isolation precautions has not been assessed. Added value of this studyBased on the active follow-up of households of health care workers from the Sheba Medical Center in Israel, we estimated the effect of vaccination on household transmission. To our knowledge, our study is the first to conjointly investigate the effect of vaccination, age, and isolation precautions on the risk of infection and the risk of transmission in households while accounting for tertiary infections in the household, infections within the community, the reduced infectivity of asymptomatic cases, misidentification of index cases, and household size. Our study confirmed the high efficacy of BNT-162b2 vaccination to reduce infection risk and transmission risk. It also suggests that isolation might remain beneficial to vaccinated contacts. Implications of all the available evidenceVaccination reduces susceptibility to infection and case infectivity in households. Isolation precautions also mitigate the risk of infection and should be implemented whenever a household member is infected. They might remain beneficial to vaccinated contacts.

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

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.

Impact of national and regional lockdowns on COVID-19 epidemic waves: Application to the 2020 spring wave in France

Several countries have implemented lockdowns to control their COVID-19 epidemic. However, questions like "where" and "when" still require answers. We assessed the impact of national and regional lockdowns considering the French first epidemic wave of COVID-19 as a case study. In a regional lockdown scenario aimed at preventing intensive care units (ICU) saturation, almost all French regions would have had to implement a lockdown within 10 days and 96% of ICU capacities would have been used. For slowly growing epidemics, with a lower reproduction number, the expected delays between regional lockdowns increases. However, the public health costs associated with these delays tend to grow exponentially with time. In a quickly growing pandemic wave, defining the timing of lockdowns at a regional rather than national level delays by a few days the implementation of a nationwide lockdown but leads to substantially higher morbidity, mortality and stress on the healthcare system.

Colder and drier winter conditions are associated with greater SARS-CoV-2 transmission: a regional study of the first epidemic wave in north-west hemisphere countries.

Higher transmissibility of SARS-CoV-2 in cold and dry weather conditions has been hypothesized since the onset of the COVID-19 pandemic but the level of epidemiological evidence remains low. During the first wave of the pandemic, Spain, Italy, France, Portugal, Canada and USA presented an early spread, a heavy COVID-19 burden, and low initial public health response until lockdowns. In a context when testing was limited, we calculated the basic reproduction number (R0) in 63 regions from the growth in regional death counts. After adjusting for population density, early spread of the epidemic, and age structure, temperature and humidity were negatively associated to SARS-CoV-2 transmissibility. A reduction of mean absolute humidity by 1g/m3 was associated with a 0.15-unit increase of R0. Below 10{degrees}C, a temperature reduction of 1{degrees}C was associated with a 0.16-unit increase of R0. Our results confirm a dependency of SARS-CoV-2 transmissibility to weather conditions in the absence of control measures during the first wave. The transition from summer-to winter-like conditions likely contributed to the intensification of the second wave in north-west hemisphere countries. Adjustments of the levels of social mobility restrictions need to account for increased SARS-CoV-2 transmissibility in winter conditions.

Monitoring the proportion infected by SARS-CoV-2 from age-stratified hospitalisation and serological data

BackgroundRegional monitoring of the proportion infected by SARS-CoV-2 is important to guide local management of the epidemic, but is difficult in the absence of regular nationwide serosurveys. MethodsWe developed a method to reconstruct in real-time the proportion infected by SARS-CoV-2 and the proportion of infections being detected from the joint analysis of age-stratified seroprevalence, hospitalisation and case data. We applied our approach to the 13 French metropolitan regions. FindingsWe estimate that 5.7% [5.1%-6.4%] of adults in metropolitan France had been infected by SARS-CoV-2 by May 2020. This proportion remained stable until August and increased to 12.6% [11.2%-14.3%] by the end of November. With 23.8% [21.2%-26.8%] infected in the Paris region compared to 4.0% [3.5% - 4.6%] in Brittany, regional variations remained large (Coefficient of Variation CV: 0.53) although less so than in May (CV: 0.74). The proportion infected was twice higher (17.6% [13.4%-22.7%]) in 20-49 y.o. than in 50+ y.o (8.0% [5.7% - 11.5%]). Forty percent [33.7% - 45.4%] of infections in adults were detected in June-August compared to 55.7% [48.7% - 63.1%] in September-November. Our method correctly predicted seroprevalence in 11 regions in which only hospitalisation data were used. InterpretationIn the absence of contemporary serosurvey, our real-time monitoring indicates that the proportion infected by SARS-CoV-2 may be above 20% in some French regions. FundingEU RECOVER, ANR, Fondation pour la Recherche Medicale, Inserm.

Comparing the age and sex trajectories of SARS-CoV-2 morbidity with other respiratory pathogens points to potential immune mechanisms.

Comparing age and sex differences in SARS-CoV-2 hospitalization and mortality with influenza and other health outcomes opens the way to generating hypotheses as to the underlying mechanisms, building on the extraordinary advances in immunology and physiology that have occurred over the last year. Notable departures in health outcomes starting around puberty suggest that burdens associated with influenza and other causes are reduced relative to the two emergent coronaviruses over much of adult life. Two possible hypotheses could explain this: protective adaptive immunity for influenza and other infections, or greater sensitivity to immunosenescence in the coronaviruses. Comparison of sex differences suggest an important role for adaptive immunity; but immunosenescence might also be relevant, if males experience faster immunosenescence. Involvement of the renin-angiotensin-system in SARS-CoV-2 infection might drive high sensitivity to disruptions of homeostasis. Overall, these results highlight the long tail of vulnerability in the age profile relevant to the emergent coronaviruses, which more transmissible variants have the potential to uncover at the younger end of the scale, and aging populations will expose at the other end of the scale.

Early chains of transmission of COVID-19 in France

IntroductionSARS-CoV-2, which causes COVID-19, has spread rapidly across the world. A dedicated surveillance system was implemented in France in January 2020 to improve early detection of cases and their contacts and limit secondary transmission. Our objective was to use contact-tracing data collected during this initial phase of the epidemic to better characterize 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 characterized the risk of a contact becoming a case. We described chains of transmission and estimated key parameters of spread. ResultsOver the study period, 6,082 contacts of 735 confirmed cases were traced. The overall secondary clinical attack rate was 4.1% (95%CI 3.6-4.6) and increased with age of the index case and of the contact. Family contacts were at higher risk of becoming cases (adjusted odds ratio 2.1 (95%CI 1.4-3.0)) while nosocomial contacts were at lower risk (adjusted odds ratio 0.3 (95%CI 0.1-0.7)), compared to coworkers/friends. We identified 328 infector/infectee pairs, 49% of which were family members. The distribution of secondary cases was highly over-dispersed with 80% of secondary cases being caused by 10% of cases. The mean serial interval was 5.1 days (interquartile range 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 contributes to improving our knowledge of SARS-CoV-2 transmission, such as the importance of superspreading events. Contact-tracing data are challenging to collect but are key to better understand emerging pathogens. Funding statementThis work was supported by the LabEx "Integrative Biology of Emerging Infectious Diseases (IBEID)" (Grant Number ANR-10-LABX-62-IBEID), Sante Publique France, the INCEPTION project (PIA/ANR-16-CONV-0005), and the European Unions Horizon 2020 research and innovation program under grants 101003589 (RECOVER) and 874735 (VEO).

Ready for a BASE jump? Do not neglect SARS-CoV-2 hospitalization and fatality risks in the middle-aged adult population.

Seroprevalence results coupled with surveillance data were used to estimate the SARS-CoV-2 infection hospitalization (IHR) and infection fatality ratios (IFR) in France. IHR and IFR were dramatically high in the very elderly (80-90 years: IHR: 30%, IFR: 11%), but also substantial in middle-aged adults (40-50 years: IHR: 1.2%, IFR: 0.05%).

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 reduced the basic reproduction number of SARS-CoV-2 from 1.7 to 1.1, which was sufficient to avoid saturation of hospitals. We estimate that thanks to the young demographics across the territory, 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 modeling can be used to support healthcare planning and decision making in a context of high uncertainty.

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

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 populations 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.

Seroprevalence of anti-SARS-CoV-2 IgG at the epidemic peak in French Guiana

Background SARS-CoV-2 seroprevalence studies are crucial for clarifying dynamics in affected countries and determining the route that has already been achieved towards herd immunity. While Latin America has been heavily affected by the pandemic, only a few seroprevalence studies have been conducted there. Methods A cross-sectional survey was performed between 15 July 2020 and 23 July 2020 in 4 medical biology laboratories and 5 health centers of French Guiana, representing a period shortly after the epidemic peak. Samples were screened for the presence of anti-SARS-CoV-2 IgG directed against domain S1 of the SARS-CoV-2 spike protein using the anti-SARS-CoV-2 enzyme-linked immunosorbent assay (ELISA) from Euroimmun. Results The overall seroprevalence was 15.4% [9.3%-24.4%] among 480 participants, ranging from 4.0% to 25.5% across the different municipalities. The seroprevalence did not differ according to gender (p=0.19) or age (p=0.51). Among SARS-CoV-2 positive individuals, we found that 24.6% [11.5%-45.2%] reported symptoms consistent with COVID-19. Conclusions Our findings revealed high levels of infection across the territory but a low number of resulting deaths, which can be explained by the young population structure.

Age-specific mortality and immunity patterns of SARS-CoV-2 infection in 45 countries

The number of COVID-19 deaths is often used as a key indicator of SARS-CoV-2 epidemic size. However, heterogeneous burdens in nursing homes and variable reporting of deaths in elderly individuals can hamper comparisons of deaths and the number of infections associated with them across countries. Using age-specific death data from 45 countries, we find that relative differences in the number of deaths by age amongst individuals aged <65 years old are highly consistent across locations. Combining these data with data from 15 seroprevalence surveys we demonstrate how age-specific infection fatality ratios (IFRs) can be used to reconstruct infected population proportions. We find notable heterogeneity in overall IFR estimates as suggested by individual serological studies and observe that for most European countries the reported number of deaths amongst [≥]65s are significantly greater than expected, consistent with high infection attack rates experienced by nursing home populations in Europe. Age-specific COVID-19 death data in younger individuals can provide a robust indicator of population immunity.