Importance The degree to which children and adolescents are infected by and transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear. The role of children and adolescents in transmission of SARS-CoV-2 is dependent on susceptibility, symptoms, viral load, social contact patterns, and behavior. Objective To systematically review the susceptibility to and transmission of SARS-CoV-2 among children and adolescents compared with adults. Data Sources PubMed and medRxiv were searched from database inception to July 28, 2020, and a total of 13 926 studies were identified, with additional studies identified through hand searching of cited references and professional contacts. Study Selection Studies that provided data on the prevalence of SARS-CoV-2 in children and adolescents (younger than 20 years) compared with adults (20 years and older) derived from contact tracing or population screening were included. Single-household studies were excluded. Data Extraction and Synthesis PRISMA guidelines for abstracting data were followed, which was performed independently by 2 reviewers. Quality was assessed using a critical appraisal checklist for prevalence studies. Random-effects meta-analysis was undertaken. Main Outcomes and Measures Secondary infection rate (contact-tracing studies) or prevalence or seroprevalence (population screening studies) among children and adolescents compared with adults. Results A total of 32 studies comprising 41 640 children and adolescents and 268 945 adults met inclusion criteria, including 18 contact-tracing studies and 14 population screening studies. The pooled odds ratio of being an infected contact in children compared with adults was 0.56 (95% CI, 0.37-0.85), with substantial heterogeneity (I2 = 94.6%). Three school-based contact-tracing studies found minimal transmission from child or teacher index cases. Findings from population screening studies were heterogenous and were not suitable for meta-analysis. Most studies were consistent with lower seroprevalence in children compared with adults, although seroprevalence in adolescents appeared similar to adults. Conclusions and Relevance In this meta-analysis, there is preliminary evidence that children and adolescents have lower susceptibility to SARS-CoV-2, with an odds ratio of 0.56 for being an infected contact compared with adults. There is weak evidence that children and adolescents play a lesser role than adults in transmission of SARS-CoV-2 at a population level. This study provides no information on the infectivity of children.

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Susceptibility to SARS-CoV-2 Infection Among Children and Adolescents Compared With Adults: A Systematic Review and Meta-analysis.

Importance Crowded indoor environments, such as households, are high-risk settings for the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Objectives To examine evidence for household transmission of SARS-CoV-2, disaggregated by several covariates, and to compare it with other coronaviruses. Data Source PubMed, searched through October 19, 2020. Search terms includedSARS-CoV-2orCOVID-19withsecondary attack rate,household,close contacts,contact transmission,contact attack rate, orfamily transmission. Study Selection All articles with original data for estimating household secondary attack rate were included. Case reports focusing on individual households and studies of close contacts that did not report secondary attack rates for household members were excluded. Data Extraction and Synthesis Meta-analyses were done using a restricted maximum-likelihood estimator model to yield a point estimate and 95% CI for secondary attack rate for each subgroup analyzed, with a random effect for each study. To make comparisons across exposure types, study was treated as a random effect, and exposure type was a fixed moderator. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed. Main Outcomes and Measures Secondary attack rate for SARS-CoV-2, disaggregated by covariates (ie, household or family contact, index case symptom status, adult or child contacts, contact sex, relationship to index case, adult or child index cases, index case sex, number of contacts in household) and for other coronaviruses. Results A total of 54 relevant studies with 77 758 participants reporting household secondary transmission were identified. Estimated household secondary attack rate was 16.6% (95% CI, 14.0%-19.3%), higher than secondary attack rates for SARS-CoV (7.5%; 95% CI, 4.8%-10.7%) and MERS-CoV (4.7%; 95% CI, 0.9%-10.7%). Household secondary attack rates were increased from symptomatic index cases (18.0%; 95% CI, 14.2%-22.1%) than from asymptomatic index cases (0.7%; 95% CI, 0%-4.9%), to adult contacts (28.3%; 95% CI, 20.2%-37.1%) than to child contacts (16.8%; 95% CI, 12.3%-21.7%), to spouses (37.8%; 95% CI, 25.8%-50.5%) than to other family contacts (17.8%; 95% CI, 11.7%-24.8%), and in households with 1 contact (41.5%; 95% CI, 31.7%-51.7%) than in households with 3 or more contacts (22.8%; 95% CI, 13.6%-33.5%). Conclusions and Relevance The findings of this study suggest that given that individuals with suspected or confirmed infections are being referred to isolate at home, households will continue to be a significant venue for transmission of SARS-CoV-2.

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Household Transmission of SARS-CoV-2: A Systematic Review and Meta-analysis.

Long COVID is an often debilitating illness that occurs in at least 10% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. More than 200 symptoms have been identified with impacts on multiple organ systems. At least 65 million individuals worldwide are estimated to have long COVID, with cases increasing daily. Biomedical research has made substantial progress in identifying various pathophysiological changes and risk factors and in characterizing the illness; further, similarities with other viral-onset illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome have laid the groundwork for research in the field. In this Review, we explore the current literature and highlight key findings, the overlap with other conditions, the variable onset of symptoms, long COVID in children and the impact of vaccinations. Although these key findings are critical to understanding long COVID, current diagnostic and treatment options are insufficient, and clinical trials must be prioritized that address leading hypotheses. Additionally, to strengthen long COVID research, future studies must account for biases and SARS-CoV-2 testing issues, build on viral-onset research, be inclusive of marginalized populations and meaningfully engage patients throughout the research process. Long COVID is an often debilitating illness of severe symptoms that can develop during or following COVID-19. In this Review, Davis, McCorkell, Vogel and Topol explore our knowledge of long COVID and highlight key findings, including potential mechanisms, the overlap with other conditions and potential treatments. They also discuss challenges and recommendations for long COVID research and care. 

https://www.nature.com/articles/s41579-022-00846-2.pdf

Long COVID: major findings, mechanisms and recommendations

Funding: This work was supported by Award Number U54GM088558 from the National Institute of General Medical Sciences (ML, EG) and the US National Institutes of Health cooperative agreement U01 CA261277 (ML).

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On the effect of age on the transmission of SARS-CoV-2 in households, schools and the community.

Summary Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spread by direct, indirect, or close contact with infected people via infected respiratory droplets or saliva. Crowded indoor environments with sustained close contact and conversations are a particularly high-risk setting. Methods We performed a meta-analysis through July 29, 2020 of SARS-CoV-2 household secondary attack rate (SAR), disaggregating by several covariates (contact type, symptom status, adult/child contacts, contact sex, relationship to index case, index case sex, number of contacts in household, coronavirus). Findings We identified 40 relevant published studies that report household secondary transmission. The estimated overall household SAR was 18·8% (95% confidence interval [CI]: 15·4%–22·2%), which is higher than previously observed SARs for SARS-CoV and MERS-CoV. We observed that household SARs were significantly higher from symptomatic index cases than asymptomatic index cases, to adult contacts than children contacts, to spouses than other family contacts, and in households with one contact than households with three or more contacts. Interpretation To prevent the spread of SARS-CoV-2, people are being asked to stay at home worldwide. With suspected or confirmed infections referred to isolate at home, household transmission will continue to be a significant source of transmission.

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Household transmission of SARS-CoV-2: a systematic review and meta-analysis of secondary attack rate.

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 53) 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

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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.

Summary Background 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. Methods 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. Findings 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. Interpretation 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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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

Yoav Miron

Papers

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.

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