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medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.07.29.22278190


SUMMARY 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.

medrxiv; 2022.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2022.05.23.22275460


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.

medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.12.08.21267454


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.

medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.07.12.21260377


Background Massive 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. Methods From 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 2 nd dose impacted household transmission of SARS-CoV-2. Findings 210 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=0·50, 95% Credible Interval CI 0·32-0·79). Vaccination reduced the risk of infection among adults/teenagers (RR=0·19, 95% CI 0·07-0·40). Isolation reduced the risk of infection of unvaccinated adult/teenager (RR=0·11, 95% CI 0·05-0·19) and child contacts (RR=0·16, 95% CI 0·07-0·31) compared to unvaccinated adults/teenagers that did not isolate. Infectivity was significantly reduced in vaccinated cases (RR=0·22, 95% CI 0·06-0·70). Interpretation Within 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. Funding Sheba Medical Center. Research in context Evidence before this study The 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 2 nd dose, and vaccine efficacy on the risk of transmission if infected was estimated to 49% 21 days after the 1 st 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 study Based 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 evidence Vaccination 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.

COVID-19 , Coronavirus Infections , Severe Acute Respiratory Syndrome
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.01.11.21249435


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.

medrxiv; 2020.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2020.04.20.20072413


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.