Transmission of SARS-CoV-2 by children and young people in households and schools: a meta-analysis of population-based and contact-tracing studies

Background: The role of children and young people (CYP) in transmission of SARS-CoV-2 in household and educational settings remains unclear. We undertook a systematic review and meta-analysis of contact-tracing and population-based studies at low risk of bias. / Methods: We searched 4 electronic databases on 28 July 2021 for contact-tracing studies and population-based studies informative about transmission of SARS-CoV-2 from 0-19 year olds in household or educational settings. We excluded studies at high risk of bias, including from under-ascertainment of asymptomatic infections. We undertook multilevel random effects meta-analyses of secondary attack rates (SAR: contact-tracing studies) and school infection prevalence, and used meta-regression to examine the impact of community SARS-CoV-2 incidence on school infection prevalence. / Findings: 4529 abstracts were reviewed, resulting in 37 included studies (16 contact-tracing; 19 population studies; 2 mixed studies). The pooled relative transmissibility of CYP compared with adults was 0.92 (0.68, 1.26) in adjusted household studies. The pooled SAR from CYP was lower (p=0.002) in school studies 0.7% (0.2, 2.7) than household studies (7.6% (3.6, 15.9) . There was no difference in SAR from CYP to child or adult contacts. School population studies showed some evidence of clustering in classes within schools. School infection prevalence was associated with contemporary community 14-day incidence (OR 1.003 (1.001, 1.004), p<0.001). / Interpretation: We found no difference in transmission of SARS-CoV-2 from CYP compared with adults within household settings. SAR were markedly lower in school compared with household settings, suggesting that household transmission is more important than school transmission in this pandemic. School infection prevalence was associated with community infection incidence, supporting hypotheses that school infections broadly reflect community infections. These findings are important for guiding policy decisions on shielding, vaccination school and operations during the pandemic

Transmission of SARS-CoV-2 by children and young people in households and schools: A meta-analysis of population-based and contact-tracing studies.

BACKGROUND: The role of children and young people (CYP) in transmission of SARS-CoV-2 in household and educational settings remains unclear. We undertook a systematic review and meta-analysis of contact-tracing and population-based studies at low risk of bias. METHODS: We searched 4 electronic databases on 28 July 2021 for contact-tracing studies and population-based studies informative about transmission of SARS-CoV-2 from 0 to 19 year olds in household or educational settings. We excluded studies at high risk of bias, including from under-ascertainment of asymptomatic infections. We undertook multilevel random effects meta-analyses of secondary attack rates (SAR: contact-tracing studies) and school infection prevalence, and used meta-regression to examine the impact of community SARS-CoV-2 incidence on school infection prevalence. FINDINGS: 4529 abstracts were reviewed, resulting in 37 included studies (16 contact-tracing; 19 population studies; 2 mixed studies). The pooled relative transmissibility of CYP compared with adults was 0.92 (0.68, 1.26) in adjusted household studies. The pooled SAR from CYP was lower (p = 0.002) in school studies 0.7% (0.2, 2.7) than household studies (7.6% (3.6, 15.9) . There was no difference in SAR from CYP to child or adult contacts. School population studies showed some evidence of clustering in classes within schools. School infection prevalence was associated with contemporary community 14-day incidence (OR 1.003 (1.001, 1.004), p<0.001). INTERPRETATION: We found no difference in transmission of SARS-CoV-2 from CYP compared with adults within household settings. SAR were markedly lower in school compared with household settings, suggesting that household transmission is more important than school transmission in this pandemic. School infection prevalence was associated with community infection incidence, supporting hypotheses that school infections broadly reflect community infections. These findings are important for guiding policy decisions on shielding, vaccination school and operations during the pandemic

f(R) theories

Over the past decade, f(R) theories have been extensively studied as one of the simplest modifications to General Relativity. In this article we review various applications of f(R) theories to cosmology and gravity - such as inflation, dark energy, local gravity constraints, cosmological perturbations, and spherically symmetric solutions in weak and strong gravitational backgrounds. We present a number of ways to distinguish those theories from General Relativity observationally and experimentally. We also discuss the extension to other modified gravity theories such as Brans-Dicke theory and Gauss-Bonnet gravity, and address models that can satisfy both cosmological and local gravity constraints.Comment: 156 pages, 14 figures, Invited review article in Living Reviews in Relativity, Published version, Comments are welcom

CD28/B7-Mediated Co-stimulation Is Critical for Early Control of Murine Cytomegalovirus Infection

Abstract Control of acute murine cytomegalovirus (MCMV) infection is dependent upon both innate and adaptive immune responses, relying primarily upon natural killer (NK) and T-cell responses for control. Although CD28/B7 plays a clear role in T-cell responses in many antigen systems including some viral infections, the importance of co-stimulation during MCMV infection is unconfirmed. In addition, recent data suggest that CD28/B7 co-stimulation might also be important to Ly49H+ NK-cell expansion. We therefore hypothesized that CD28/B7 co-stimulation is critical to viral control after MCMV infection, and further that CD28/B7 co-stimulation plays a role in MCMV-specific T- and NK-cell responses. To test these hypotheses, we utilized C57BL/6 mice lacking the co-stimulatory molecules B7-1 and B7-2 or CD28. After primary infection with MCMV, viral titers are significantly elevated in mice lacking CD28 or B7 compared with wild-type mice. Impaired viral control is associated with significant defects in peripheral T-cell responses to MCMV, which appear to be dependent upon CD28/B7 co-stimulation. Abnormal hepatic T-cell responses in CD28/ mice are preceded by impaired MCMV-specific Ly49H+ NK-cell responses. Cytokine evaluations confirm that CD28/B7 co-stimulation is not required for non-specific antiviral responses. We conclude that CD28-mediated co-stimulation is critical for early viral control during acute MCMV infection.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78134/1/vim.2008.0080.pd

Cost-Effective Strategies for Mitigating a Future Influenza Pandemic with H1N1 2009 Characteristics

Background: We performed an analysis of the cost-effectiveness of pandemic intervention strategies using a detailed, individual-based simulation model of a community in Australia together with health outcome data of infected individuals gathered during 2009–2010. The aim was to examine the cost-effectiveness of a range of interventions to determine the most cost-effective strategies suitable for a future pandemic with H1N1 2009 characteristics. Methodology/Principal Findings: Using transmissibility, age-stratified attack rates and health outcomes determined from H1N1 2009 data, we determined that the most cost-effective strategies involved treatment and household prophylaxis using antiviral drugs combined with limited duration school closure, with costs ranging from $632 to$777 per case prevented. When school closure was used as a sole intervention we found the use of limited duration school closure to be significantly more cost-effective compared to continuous school closure, a result with applicability to countries with limited access to antiviral drugs. Other social distancing strategies, such as reduced workplace attendance, were found to be costly due to productivity losses. Conclusion: The mild severity (low hospitalisation and case fatality rates) and low transmissibility of H1N1 2009 meant that health treatment costs were dominated by the higher productivity losses arising from workplace absence due to illness and childcare requirements following school closure. Further analysis for higher transmissibility but with the same, mild severit

Human Th1 Cells That Express CD300a Are Polyfunctional and After Stimulation Up-Regulate the T-Box Transcription Factor Eomesodermin

Human naïve CD4 T cells express low levels of the immunomodulatory receptor CD300a, whereas effector/memory CD4 cells can be either CD300a+ or CD300a−. This suggested that CD300a expression could define a specific subset within the effector/memory CD4 T cell subpopulations. In fact, ex vivo analysis of the IFN-γ producing CD4 T cells showed that they are enriched in the CD300a+ subset. Moreover, stimulated CD4 T cells producing TNF-α and IL-2 besides IFN-γ (polyfunctional) are predominantly CD300a+. In addition to producing markedly higher levels of Th1-associated cytokines, the stimulated CD300a+ CD4 T cells are distinguished by a striking up-regulation of the T-box transcription factor eomesodermin (Eomes), whereas T-bet is up-regulated in both CD300a+ and CD300a− activated CD4 T cells to similar levels. The pleiotropic cytokine TGF-β1 has a determinant role in dictating the development of this Th1 subset, as its presence inhibits the expression of CD300a and down-regulates the expression of Eomes and IFN-γ. We conclude that CD300a+ human Th1 cells tend to be polyfunctional and after stimulation up-regulate Eomes