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.

One of the significant unanswered questions about COVID-19 epidemiology relates to the role of children in transmission. In this study we estimate susceptibility and infectivity of children compared to those of adults. Understanding the age-structured transmission dynamics of the outbreak provides precious and timely information to guide epidemic modelling and public health policy. Data were collected from households in the city of Bnei Brak, Israel, in which all household members were tested for COVID-19 using PCR. To estimate relative transmission parameters in the absence of data on who infected whom, we developed an estimation method based on a discrete stochastic dynamic model of the spread of the epidemic within a household. The model describes the propagation of the disease between household members allowing for susceptibility and infectivity parameters to vary among two age groups. The parameter estimates are obtained by a maximum likelihood method, where the likelihood function is computed based on the stochastic model via simulations. Inspection of the data reveals that children are less likely to become infected compared to adults (25% of children infected over all households, 44% of adults infected over all households, excluding index cases), and the chances of becoming infected increases with age. An interesting exception is that infants up to age one year are more likely to be infected than children between one and four. Using our modelling approach, we estimate that the susceptibility of children (under 20 years old) is 45% [40%, 55%] of the susceptibility of adults. The infectivity of children was estimated to be 85% [65%,110%] relative to that of adults. It is widely observed that the percentage of children within confirmed cases is low. A common explanation is that children who are infected are less likely to develop symptoms than adults, and thus are less likely to be tested. We estimate that children are less susceptible to infection, which is an additional factor explaining their relatively low rate of occurrence within confirmed cases. Moreover, our results indicate that children, when infected, are somewhat less prone to infect others compared to adults; however, this result is not statistically significant. The resulting estimates of susceptibility and infectivity of children compared to adults are crucial for deciding on appropriate interventions, and for controlling the epidemic outbreak and its progress. These estimates can guide age-dependent public health policy such as school closure and opening. However, while our estimates of children's susceptibility and infectivity are lower than those of adults within a household, it is important to bear in mind that their role in the spread of COVID-19 outside the household, is also affected by different contact patterns and hygiene habits.

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SummaryIn the present study we analyzed changes in the pattern of gene expression in endothelial cells (HUVEC) exposed to elevated homocysteine levels under flow conditions. RNA samples of untreated and homocysteine treated EC were analyzed using a human cDNA array containing 588 cDNAs relevant to the cardiovascular system. Exposure to homocysteine under flow resulted in altered expression of 8 genes, the alterations of 3 of which were further confirmed by RT-PCR analysis: upregulation of MCP-1 and of profilin-I, and downregulation of alpha-catenin. The increased expression of profilin-I and the decreased expression of alpha-catenin were also confirmed at the protein level by Western blot analysis. Furthermore, immunostaining for alpha-catenin demonstrated complete loss of the protein from intercellular junctions following exposure to homocysteine under flow. All these changes were not observed in cells exposed to homocysteine under static conditions. We show that under flow conditions, homocysteine modulates the expression of genes/proteins involved in actin cytoskeleton reorganization, as well as in the formation and/or maintenance of cellcell junction, thus contributing to the morphological changes (e.g. cell retraction) reflecting endothelial cell injury.