Data-driven clustering of infectious disease incidence into age groups.

Understanding the patterns of infectious diseases spread in the population is an important element of mitigation and vaccination programs. A major and common characteristic of most infectious diseases is age-related heterogeneity in the transmission, which potentially can affect the dynamics of an epidemic as manifested by the pattern of disease incidence in different age groups. Currently there are no statistical criteria of how to partition the disease incidence data into clusters. We develop the first data-driven methodology for deciding on the best partition of incidence data into age-groups, in a well defined statistical sense. The method employs a top-down hierarchical partitioning algorithm, with a stopping criteria based on multiple hypotheses significance testing controlling the family wise error rate. The type one error and statistical power of the method are tested using simulations. The method is then applied to Covid-19 incidence data in Israel, in order to extract the significant age-group clusters in each wave of the epidemic.

Similarity of Protection Conferred by Previous SARS-CoV-2 Infection and by BNT162b2 Vaccine: A 3-Month Nationwide Experience From Israel.

The worldwide shortage of vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection while the pandemic still remains uncontrolled has led many countries to the dilemma of whether or not to vaccinate previously infected persons. Understanding the level of protection conferred by previous infection compared with that of vaccination is important for policy-making. We analyzed an updated individual-level database of the entire population of Israel to assess the protection provided by both prior infection and vaccination in preventing subsequent SARS-CoV-2 infection, hospitalization with coronavirus disease 2019 (COVID-19), severe disease, and death due to COVID-19. Outcome data were collected from December 20, 2020, to March 20, 2021. Vaccination was highly protective, with overall estimated effectiveness of 94.5% (95% confidence interval (CI): 94.3, 94.7) for documented infection, 95.8% (95% CI: 95.2, 96.2) for hospitalization, 96.3% (95% CI: 95.7, 96.9) for severe illness, and 96.0% (95% CI: 94.9, 96.9) for death. Similarly, the overall estimated level of protection provided by prior SARS-CoV-2 infection was 94.8% (95% CI: 94.4, 95.1) for documented infection, 94.1% (95% CI: 91.9, 95.7) for hospitalization, and 96.4% (95% CI: 92.5, 98.3) for severe illness. Our results should be considered by policy-makers when deciding whether or not to prioritize vaccination of previously infected adults.

Population-level implications of the Israeli booster campaign to curtail COVID-19 resurgence.

Israel was one of the first countries to administer mass vaccination against severe acute respiratory syndrome coronavirus 2. Consequently, it was among the first countries to experience substantial breakthrough infections due to the waning of vaccine-induced immunity, which led to a resurgence of the epidemic. In response, Israel launched a booster campaign to mitigate the outbreak and was the first country to do so. Israel's success in curtailing the Delta resurgence while imposing only mild nonpharmaceutical interventions influenced the decision of many countries to initiate a booster campaign. By constructing a detailed mathematical model and calibrating it to the Israeli data, we extend the understanding of the impact of the booster campaign from the individual to the population level. We used the calibrated model to explore counterfactual scenarios in which the booster vaccination campaign is altered by changing the eligibility criteria or the start time of the campaign and to assess the direct and indirect effects in the different scenarios. The results point to the vast benefits of vaccinating younger age groups that are not at a high risk of developing severe disease but play an important role in transmission. We further show that, when the epidemic is exponentially growing, the success of the booster campaign is highly sensitive to the timing of its initiation. Hence, a rapid response is an important factor in reducing disease burden using booster vaccination.

The role of children in the spread of COVID-19: Using household data from Bnei Brak, Israel, to estimate the relative susceptibility and infectivity of children.

One of the significant unanswered questions about COVID-19 epidemiology relates to the role of children in transmission. This study uses data on infections within households in order to estimate the susceptibility and infectivity of children compared to those of adults. The data were collected from households in the city of Bnei Brak, Israel, in which all household members were tested for COVID-19 using PCR (637 households, average household size of 5.3). In addition, serological tests were performed on a subset of the individuals in the study. Inspection of the PCR data shows that children are less likely to be tested positive compared to adults (25% of children positive over all households, 44% of adults positive over all households, excluding index cases), and the chance of being positive increases with age. Analysis of joint PCR/serological data shows that there is under-detection of infections in the PCR testing, which is more substantial in children. However, the differences in detection rates are not sufficient to account for the differences in PCR positive rates in the two age groups. To estimate relative transmission parameters, we employ a discrete stochastic model of the spread of infection within a household, allowing for susceptibility and infectivity parameters to differ among children and adults. The model is fitted to the household data using a simulated maximum likelihood approach. To adjust parameter estimates for under-detection of infections in the PCR results, we employ a multiple imputation procedure using estimates of under-detection in children and adults, based on the available serological data. We estimate that the susceptibility of children (under 20 years old) is 43% (95% CI: [31%, 55%]) of the susceptibility of adults. The infectivity of children was estimated to be 63% (95% CI: [37%, 88%]) relative to that of adults.