Statistical and agent-based modelling of the transmissibility of different SARS-CoV-2 variants in England and impact of different interventions

The English SARS-CoV-2 epidemic has been affected by the emergence of new viral variants such as B.1.177, Alpha and Delta, and changing restrictions. We used statistical models and calibration of an stochastic agent-based model Covasim to estimate B.1.177 to be 20% more transmissible than the wild type, Alpha to be 50-80% more transmissible than B.1.177 and Delta to be 65-90% more transmissible than Alpha. We used these estimates in Covasim (calibrated between September 01, 2020 and June 20, 2021), in June 2021, to explore whether planned relaxation of restrictions should proceed or be delayed. We found that due to the high transmissibility of Delta, resurgence in infections driven by the Delta variant would not be prevented, but would be strongly reduced by delaying the relaxation of restrictions by one month and with continued vaccination.

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

BackgroundThe 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. MethodsWe 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. Findings4529 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). InterpretationWe 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. FundingNo funding obtained.

The impact of race and socioeconomic factors on paediatric diabetes.

There are over 29,000 children and young people (CYP) with Type 1 diabetes mellitus (T1DM) in England and Wales and another 726 with Type 2 diabetes mellitus (T2DM). There is little effect of deprivation on the prevalence of T1DM whereas the association of deprivation on the percentage of CYP with T2DM is striking with 45% of cases drawn from the most deprived backgrounds. A number that has not changed over the last 4 years. Data from the UK and USA as well as other countries demonstrate the impact of deprivation on outcomes in diabetes mellitus with clear effects on measures of long-term control and complications. In the UK black CYP had higher glycosylated haemoglobin (HbA1c) values compared to other groups. Within the black group, CYP from a Caribbean background had a higher mean HbA1c (77.0 mmol/mol (9.2%)) than those from Africa (70.4 mmol/mol (8.6%)). Treatment regimen (multiple daily injections or insulin pump therapy) explained the largest proportion of the variability in HbA1c followed by deprivation. Those in the least deprived areas had an average HbA1c 5.88 mmol/mol (0.5%) lower than those living in the most deprived areas. The picture is complex as UK data also show that deprivation and ethnicity is associated with less use of technology that is likely to improve diabetes control. Increased usage of pump therapy and continuous glucose monitoring was associated with a younger age of patient (less than 10 years of age), living in the least deprived areas and white ethnicity. This gap between pump usage amongst CYP with T1DM living in the most and least deprived areas has widened with time. In 2014/15 the gap was 7.9% and by 2018/19 had increased to 13.5%. To attain an equitable service for CYP with diabetes mellitus we need to consider interventions at the patient, health care professional, community, and health care system levels.

Which children and young people are at higher risk of severe disease and death after SARS-CoV-2 infection: a systematic review and individual patient meta-analysis

BackgroundWe aimed to use individual patient data to describe pre-existing factors associated with severe disease, primarily admission to critical care, and death secondary to SARS-CoV-2 infection in children and young people (CYP) in hospital. MethodsWe searched Pubmed, European PMC, Medline and Embase for case series and cohort studies that included all CYP admitted to hospital with [≥]30 CYP with SARS-CoV-2 or [≥]5 CYP with PIMS-TS or MIS-C. Eligible studies contained 1) details of age, sex, ethnicity or co-morbidities, and 2) an outcome which included admission to critical care, mechanical invasive ventilation, cardiovascular support, or death. Studies reporting outcomes in more restricted grouping of co-morbidities were eligible for narrative review. Authors of eligible studies were approached for individual patient data (IPD). We used random effects meta-analyses for aggregate study-level data and multilevel mixed effect models for IPD data to examine risk factors (age, sex, comorbidities) associated with admission to critical care and death. Data shown are odds ratios and 95% confidence intervals (CI). Findings81 studies were included, 57 in the meta-analysis (of which 22 provided IPD) and 26 in the narrative synthesis. Most studies had an element of bias in their design or reporting. Sex was not associated with critical care or death. Compared with CYP aged 1-4 years, infants had increased odds of admission to critical care (OR 1.63 (95% CI 1.40-1.90)) and death (OR 2.08 (1.57-2.86)). Odds of death were increased amongst CYP over 10 years (10-14 years OR 2.15 (1.54-2.98); >14 years OR 2.15 (1.61-2.88)). Number of comorbid conditions was associated with increased odds of admission to critical care and death for COVID-19 in a dose-related fashion. For critical care admission odds ratios were: 1 comorbidity 1.49 (1.45-1.53); 2 comorbidities 2.58 (2.41-2.75); [≥]3 comorbidities 2.97 (2.04-4.32), and for death: 1 comorbidity 2.15 (1.98-2.34); 2 comorbidities 4.63 (4.54-4.74); [≥]3 co-morbidities 4.98 (3.78-6.65). Odds of admission to critical care were increased for all co-morbidities apart from asthma (0.92 (0.91-0.94)) and malignancy (0.85 (0.17-4.21)) with an increased odds of death in all co-morbidities considered apart from asthma. Neurological and cardiac comorbidities were associated with the greatest increase in odds of severe disease or death. Obesity increased the odds of severe disease and death independently of other comorbidities. InterpretationHospitalised CYP at greatest vulnerability of severe disease or death from SARS-CoV-2 infection are infants, teenagers, those with cardiac or neurological conditions, or 2 or more comorbid conditions, and those who are obese. These groups should be considered higher priority for vaccination and for protective shielding when appropriate. Whilst odds ratios were high, the absolute increase in risk for most comorbidities was small compared to children without underlying conditions. FundingRH is in receipt of a funded fellowship from Kidney Research UK. JW is in receipt of a Medical Research Council Fellowship. Putting Research Into ContextO_ST_ABSEvidence before this studyC_ST_ABSThe risk factors for severe disease following SARS-CoV-2 infection in adults has been extensively studied and reported, with good evidence that increasing age, non-white ethnicity, male gender and co-morbidities increase the risk. SARS-CoV-2 infection in children and young people (CYP) infrequently results in hospital admission and very rarely causes severe disease and death, making it difficult to discern the impact of a range of potential risk factors for severe disease in the many small to moderate sized published studies. More recent larger publications have aimed to address this question in specific populations but the global experience has not been described. We searched Pubmed, European PMC, Medline and Embase from the 1st January 2020 to 21st May 2021 for case series and cohort studies that included all CYP admitted to hospital with 30 children with reverse transcriptase-PCR confirmed SARS-CoV-2 or 5 CYP defined as having PIMS-TS or MIS-C. 57 studies met the eligibility criteria for meta-analysis. Added value of this studyTo our knowledge, this is the first meta-analysis to use individual patient data to compare the odds and risk of critical care admission and death in CYP with COVID-19 and PIMS-TS. We find that the odds of severe disease in hospitalised children is increased in those with multiple co-morbidities, cardiac and neurological co-morbidities and those who are obese. However, the additional risk compared to children without co-morbidity is small. Implications of all the available evidenceSevere COVID-19 and PIMS-TS, whilst rare, can occur in CYP. We have identified pre-existing risk factors for severe disease after SARS-CoV-2 and recommend that those with co-orbidities which place them in the highest risk groups are prioritised for vaccination.

Deaths in Children and Young People in England following SARS-CoV-2 infection during the first pandemic year: a national study using linked mandatory child death reporting data

BackgroundDeaths in children and young people (CYP) following SARS-CoV-2 infection are rare. Quantifying the risk of mortality is challenging because of high relative prevalence of asymptomatic and non-specific disease manifestations. Therefore, it is important to differentiate between CYP who have died of SARS-CoV-2 and those who have died of an alternative disease process but coincidentally tested positive. MethodsDuring the pandemic, the mandatory National Child Mortality Database (NCMD) was linked to Public Health England (PHE) testing data to identify CYP (<18 years) who died with a positive SARS-CoV-2 test. A clinical review of all deaths from March 2020 to February 2021 was undertaken to differentiate between those who died of SARS-CoV-2 infection and those who died of an alternative cause but coincidentally tested positive. Then, using linkage to national hospital admission data, demographic and comorbidity details of CYP who died of SARS-CoV-2 were compared to all other deaths. Absolute risk of death was estimated where denominator data were available. Findings3105 CYP died from all causes during the first pandemic year in England. 61 of these deaths occurred in CYP who tested positive for SARS-CoV-2. 25 CYP died of SARS-CoV-2 infection; 22 from acute infection and three from PIMS-TS. 99{middle dot}995% of CYP with a positive SARS-CoV-2 test survived. The 25 CYP who died of SARS-CoV-2 equates to a mortality rate of 2/million for the 12,023,568 CYP living in England. CYP >10 years, of Asian and Black ethnic backgrounds, and with comorbidities were over-represented compared to other children. InterpretationSARS-CoV-2 is very rarely fatal in CYP, even among those with underlying comorbidities. These findings are important to guide families, clinicians and policy makers about future shielding and vaccination. FundingRH is in receipt of a fellowship from Kidney Research UK. JW is in receipt of a Medical Research Council Fellowship. LF is in receipt of funding from Martin House Childrens Hospice.

Risk factors for intensive care admission and death amongst children and young people admitted to hospital with COVID-19 and PIMS-TS in England during the first pandemic year

Identifying which children and young people (CYP) are vulnerable to severe disease following SARS-CoV-2 is important to guide shielding and vaccination policy. MethodsWe used data for all inpatient hospital admissions in England in CYP aged 0-17 between March 1st 2015 to Feb 28th 2021, linked to paediatric intensive care unit (PICU), SARS-CoV-2 PCR testing, and mortality data. We examined associations between PICU admission and death by sociodemographic factors and comorbidities within COVID-19 and PIMS-TS admissions. We calculated odds ratios and predicted probability of PICU admission using generalized estimation equations, and compared these between COVID-19, PIMS-TS, other admissions in 2020/21, all admissions in 2019/20, and admissions due to influenza in 20219/20. Analyses of deaths were descriptive due to low numbers. FindingsWithin COVID-19, there were 6,338 hospital admissions, 259 PICU admissions and 8 deaths. Within PIMS-TS there were 712 hospital admissions 312 PICU admissions and <5 deaths. Males were 52.8% of COVID-19 admissions (similar to other causes of admission), but were 63.5% of PIMS-TS admissions. CYP aged 10-17 were 35.6 and 29% of COVID-19 and PIMS-TS admissions respectively, higher than in all admission and influenza admissions in 2019/20. In multivariable models, odds of PICU admission were: increased amongst neonates and decreased amongst 15-17 compared with 1-4 year olds with COVID-19, increased in older CYP and females with PIMS-TS, and increased for Black compared with White ethnicity in COVID-19 and PIMS-TS. Odds of PICU admission with COVID-19 were increased for CYP with any comorbidity and were highest for CYP with multiple medical problems. Increases in risk of PICU admission associated with comorbidities showed similar patterns for COVID-19 and all admissions in 2019/20 and influenza admissions in 2019/20, but were greater for COVID-19. Interpreting associations with comorbidities within PIMS-TS was complex due to the multisystem nature of the disease. InterpretationCYP were at very low risk of severe disease and death from COVID-19 or PIMS-TS. PICU admission due to PIMS-TS was associated with older non-white CYP. Patterns of vulnerability for severe COVID-19 appear to magnify background risk factors for serious illness in CYP. Evidence before this studyWe conducted a systematic review and meta-analysis of studies investigating risk factors associated with severe disease among children and young people admitted with COVID-19 and PIMS-TS, [Harwood, R et al. 2021 (submission to the Lancet linked with this paper)]. We identified 81 studies. Infants were found to have increased odds of PICU admission compared with 1-4, but there were no associations by sex. Other factors associated with PICU admission included number of co-morbid conditions, with neurological, cardiac and gastrointestinal associated with the greatest risk. Low numbers of serious SARS-CoV-2 infections or deaths amongst CYP limit these analyses, yet national studies of CYP have not yet been published. Importantly, we found these studies did not take into account background risks for severe illness in CYP who are known to be vulnerable before the pandemic. What this study addsThis is the first population base study of risk factors for severe disease following SARS-CoV-2 infection in CYP in England. We analyse all admissions to hospital amongst 0-17 year olds nationally between 2015-2021 linked to multiple other health datasets. We explore how socioeconomic factors and co-morbidities are associated with Paediatric Intensive Care Unit (PICU) admission and death amongst CYP admitted with COVID-19 and PIMS-TS, and compare this with other causes for admission during the pandemic and in the year prior. As CYP with PIMS-TS are highly likely to require hospitalization, we were able to analyse total national cases of the condition during 2020/21. We found extremely low numbers of CYP required PICU or died as a result of SARS-CoV-2 in the first pandemic year. CYP admitted due to COVID-19 disease were older and more likely to be non-white with pre-existing conditions, similar to patterns seen in adults. Patterns of associations between comorbidities and risk of PICU admission amongst COVID-19 were similar to those seen for all admissions and influenza admissions in the year prior to the pandemic. However, the increase in risk associated with comorbidities for COVID-19 admissions were greater than in these cohorts. We found most cases of PIMS-TS were amongst non-white male adolescents without previous hospital admissions. Interpreting associations between comorbidities and PICU admission for PIMS-TS was complicated by the multi-system nature of the disease. Implications of all the available evidenceCYP with most vulnerable to COVID-19 were also those most at risk of prior to the pandemic due to other illnesses such as influenza, although COVID-19 appears to amplify this risk profile. It is important to consider this context when advising parents and carers regarding the risk posed by COVID-19, considering potential harms to CYP as a result of shielding precautions.

Recent and forecast post-COVID trends in hospital activity in England amongst 0 to 24 year olds: analyses using routine hospital administrative data

BackgroundIncreasing hospital use in the past decade has placed considerable strain on children and young peoples (CYP) health services in England. Greater integration of healthcare may reduce these increases. We projected CYP healthcare activity out to 2040 and examined the potential impact of integrated care systems on projected activity. MethodsWe used routine administrative data (Hospital Episode Statistics (HES)) on emergency department (ED) attendances, emergency admissions and outpatient (OP) attendances for England by age-group for 0-24 year olds from 2007 to 2017. Bayesian projections of future activity used projected population and ethnicity and future child poverty rates. Cause data were used to identify ambulatory-care-sensitive-conditions (ACSC). FindingsED attendances, emergency admissions and OP attendances increased in all age groups from 2007 to 2017. ED and OP attendances increased 60-80% amongst children under 10 years. ACSC and neonatal causes drove the majority of increases in emergency admissions. Activity was projected to increase by 2040 by 50-145% for ED attendances, 20-125% for OP attendances and 4-58% for total admissions. Scenarios of increasing or decreasing child poverty resulted in small changes to forecast activity. Scenarios in which 50% of ACSC were seen outside hospital in integrated care reduced estimated activity in 2040 by 21.2-25.9% for admissions and 23.5-30.1% for ED attendances across poverty scenarios amongst infants. InterpretationThe rapid increases in CYP healthcare activity seen in the past decade may continue for the next decade given projected changes in population and child poverty, unless some of the drivers of increased activity are addressed. Contrary to these pessimistic scenarios, our findings suggest that development of integrated care for CYP at scale in England has the potential to dramatically reduce or even reverse these forecast increases FundingNil funding obtained. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThere has been marked increases in hospital use (inpatient, outpatient and emergency department (ED)) by children and young people (CYP). Search of the PubMed database using the search terms: ((((("child"[MeSH Major Topic]) OR ("adolescent"[MeSH Major Topic])) OR ("infant"[MeSH Major Topic]))) AND ((healthcare use[Text Word])) OR (emergency admission[Text Word])) AND (united kingdom[Text Word]). Drivers of increased activity include population growth and sociodemographic factors, help-seeking behaviour, growth in medical knowledge and capability, and by factors within the health system. Additional factors in child health include increased survival of premature neonates and those with congenital conditions and rising parental expectations of modern medicine. Previous studies have shown that ambulatory-care-sensitive-conditions (ACSC) are responsible for much of the increase in CYP emergency activity in England and Scotland. Added value of this studyThis is the first study to use existing data to project possible future scenarios for CYP healthcare activity out to 2030 and 2040 in any country. Our future scenarios are based upon authoritative projections for population, ethnic diversity and child poverty in England and allow us to estimate the potential impact of integrated care scenarios in which ACSC are treated outside hospital. We show that future projected CYP activity is very high if mitigations such as integrated care are not instituted in England. Implications of all the available evidenceHealthcare activity has grown dramatically over the last decade in CYP, largely due to ACSC and the consequences of premature delivery. Projections to 2040 suggest that similar increases are likely over the next 2 decades without action to reduce child poverty and implementation of integrated care at scale in the NHS.

Impacts of school closures on physical and mental health of children and young people: a systematic review

BackgroundThe well-documented links between education and health mean that school closures during the COVID-19 pandemic are likely to be associated with significant health harms to children and young people (CYP). A systematic review of the evidence is needed to inform policy decisions around school closures and re-openings during the pandemic. MethodsWe undertook a high-quality systematic review of observational quantitative studies (published or preprint) of the impacts of school closures (for any reason) on the health, wellbeing and educational outcomes of CYP, excluding impacts of closure on transmission of infection (PROSPERO CRD42020181658). We used a machine learning approach for screening articles, with decisions on inclusion and data extraction performed independently by 2 researchers. Quality was assessed for study type. A narrative synthesis of results was undertaken as data did not allow meta-analysis. Results16,817 records were screened, of which 151 were reviewed in full-text and 72 studies were included from 20 countries. 33% were cohort studies using historical control periods; 19% pre-post studies; and 46% cross-sectional studies which assessed change by comparison with population reference data. 63% were high-quality, 25% medium-quality and 13% low-quality. Cause of closure in all studies was the first COVID-19 pandemic wave with the exception of 5 influenza studies and 1 teacher strike. 27 studies concerning mental health identified considerable impacts across emotional, behavioural and restlessness/inattention problems; 18-60% of CYP scored above risk thresholds for distress, particularly anxiety and depressive symptoms. Two studies reported non-significant rises in suicide rates. Self-harm and psychiatric attendances were markedly reduced, indicating a rise in unmet mental health need. Child protection referrals fell 27-39%, with a halving of the expected number of referrals originating in schools. 19 studies concerning health service use showed marked reductions in emergency department (ED) presentations and hospital admissions, with evidence of delayed presentations and potential widening of inequalities in vaccination coverage. Data suggested marked rises in screen-time and social media use and reductions in physical activity however data on sleep and diet were inconclusive. Available data suggested likely higher harms in CYP from more deprived populations. ConclusionsSchool closures as part of broader social distancing measures are associated with considerable harms to CYP health and wellbeing. Available data are short-term and longer-term harms are likely to be magnified by further school closures. Data are urgently needed on longer-term impacts using strong research designs, particularly amongst vulnerable groups. These findings are important for policy-makers seeking to balance the risks of transmission through school-aged children with the harms of closing schools.

Modelling the impact of reopening schools in early 2021 in the presence of the new SARS-CoV-2 variant and with roll-out of vaccination against COVID-19

BackgroundFollowing the resurgence of the COVID-19 epidemic in the UK in late 2020 and the emergence of the alpha (also known as B117) variant of the SARS-CoV-2 virus, a third national lockdown was imposed from January 4, 2021. Following the decline of COVID-19 cases over the remainder of January 2021, the question of when and how to reopen schools became an increasingly pressing one in early 2021. This study models the impact of a partial national lockdown with social distancing measures enacted in communities and workplaces under different strategies of reopening schools from March 8, 2021 and compares it to the impact of continual full national lockdown remaining until April 19, 2021. MethodsWe used our previously published agent-based model, Covasim, to model the emergence of the alpha variant over September 1, 2020 to January 31, 2021 in presence of Test, Trace and Isolate (TTI) strategies. We extended the model to incorporate the impacts of the roll-out of a two-dose vaccine against COVID-19, with 200,000 daily vaccine doses prioritised by age starting with people 75 years or older, assuming vaccination offers a 95% reduction in disease acquisition risk and a 30% reduction in transmission risk. We used the model, calibrated until January 25, 2021, to simulate the impact of a full national lockdown (FNL) with schools closed until April 19, 2021 versus four different partial national lockdown (PNL) scenarios with different elements of schooling open: 1) staggered PNL with primary schools and exam-entry years (years 11 and 13) returning on March 8, 2021 and the rest of the schools years on March 15, 2020; 2) full-return PNL with both primary and secondary schools returning on March 8, 2021; 3) primary-only PNL with primary schools and exam critical years (years 11 and 13) going back only on March 8, 2021 with the rest of the secondary schools back on April 19, 2021 and 4) part-rota PNL with both primary and secondary schools returning on March 8, 2021 with primary schools remaining open continuously but secondary schools on a two-weekly rota-system with years alternating between a fortnight of face-to-face and remote learning until April 19, 2021. Across all scenarios, we projected the number of new daily cases, cumulative deaths and effective reproduction number R until April 30, 2021. ResultsOur calibration across different scenarios is consistent with alpha variant being around 60% more transmissible than the wild type. We find that strict social distancing measures, i.e. national lockdowns, were essential in containing the spread of the virus and controlling hospitalisations and deaths during January and February 2021. We estimated that a national lockdown over January and February 2021 would reduce the number of cases by early March to levels similar to those seen in October 2020, with R also falling and remaining below 1 over this period. We estimated that infections would start to increase when schools reopened, but found that if other parts of society remain closed, this resurgence would not be sufficient to bring R above 1. Reopening primary schools and exam critical years only or having primary schools open continuously with secondary schools on rotas was estimated to lead to lower increases in cases and R than if all schools opened. Without an increase in vaccination above the levels seen in January and February, we estimate that R could have increased above 1 following the reopening of society, simulated here from April 19, 2021. FindingsOur findings suggest that stringent measures were integral in mitigating the increase in cases and bringing R below 1 over January and February 2021. We found that it was plausible that a PNL with schools partially open from March 8, 2021 and the rest of the society remaining closed until April 19, 2021 would keep R below 1, with some increase evident in infections compared to continual FNL until April 19, 2021. Reopening society in mid-April, without an increase in vaccination levels, could push R above 1 and induce a surge in infections, but the effect of vaccination may be able to control this in future depending on the transmission blocking properties of the vaccines.

Do school closures reduce community transmission of COVID-19? A systematic review of observational studies

BackgroundSchool closures are associated with significant negative consequences and exacerbate inequalities. They were implemented worldwide to control SARS-CoV-2 in the first half of 2020, but their effectiveness, and the effects of lifting them, remain uncertain. This review summarises observational evidence of the effect of school closures and school reopenings on SARS-CoV-2 community transmission. MethodsThe study protocol was registered on Prospero (ID:CRD42020213699). On 07 January 2021 we searched PubMed, Web of Science, Scopus, CINAHL, the WHO Global COVID-19 Research Database, ERIC, the British Education Index, the Australian Education Index, and Google. We included observational studies with quantitative estimates of the effect of school closures/reopenings on SARS-CoV-2 community transmission. We excluded prospective modelling studies and intra-school transmission studies. We performed a narrative synthesis due to data heterogeneity. We used the ROBINS-I tool to assess risk of bias. FindingsWe identified 7,474 articles, of which 40 were included, with data from 150 countries. Of these 32 studies assessed school closures, and 11 examined reopenings. There was substantial heterogeneity between school closure studies, with half of the studies at lower risk of bias reporting reduced community transmission by up to 60%, and half reporting null findings. The majority (n=3 out of 4) of school reopening studies at lower risk of bias reported no associated increases in transmission. ConclusionsSchool closure studies were at risk of confounding and collinearity from other non-pharmacological interventions implemented around the same time as school closures, and the effectiveness of closures remains uncertain. School reopenings, in areas of low transmission and with appropriate mitigation measures, were generally not accompanied by increasing community transmission. With such varied evidence on effectiveness, and the harmful effects, policymakers should take a measured approach before implementing school closures; and should look to reopen schools in times of low transmission, with appropriate mitigation measures.

Systematic review of reviews of symptoms and signs of COVID-19 in children and adolescents

ObjectiveTo undertake a systematic review of reviews of the prevalence of symptoms and signs of COVID-19 in those aged under 20 years? DesignNarrative systematic review of reviews. PubMed, medRxiv, Europe PMC and COVID-19 Living Evidence Database were searched on 9 October 2020. SettingAll settings, including hospitalised and community settings. PatientsCYP under age 20 years with laboratory-proven COVID-19. Study review, data extraction and qualityPotentially eligible articles were reviewed on title and abstract by one reviewer. Quality was assessed using the modified AMSTARS criteria and data were extracted from included studies by two reviewers. Main outcome measuresPrevalence of symptoms and signs of COVID-19 Results1325 studies were identified and 18 reviews were included. Eight were high quality, 7 medium and 3 low quality. All reviews were dominated by studies of hospitalised children. The proportion who were asymptomatic ranged from 14.6 to 42%. Fever and cough were the commonest symptoms; proportions with fever ranged from 46 to 64.2% and with cough from 32 to 55.9%. All other symptoms or signs including rhinorrhoea, sore throat, headache, fatigue/myalgia and gastrointestinal symptoms including diarrhoea and vomiting are infrequent, occurring in less than 10-20%. ConclusionsFever and cough are the most common symptoms in CYP with COVID-19, with other symptoms infrequent. Further research on symptoms in community samples are needed to inform pragmatic identification and testing programmes for CYP.

The potential contribution of face coverings to the control of SARS-CoV-2 transmission in schools and broader society in the UK: a modelling study

Recent findings suggest that an adequate test-trace-isolate (TTI) strategy is needed to prevent a secondary COVID-19 wave with the reopening of society in the UK. Here we assess the potential importance of mandatory masks in the parts of community and in secondary schools. We show that, assuming current TTI levels, adoption of masks in secondary schools in addition to community settings can reduce the size of a second wave, but will not prevent it; more testing of symptomatic people, tracing and isolating of their contacts is also needed. To avoid a second wave, with masks mandatory in secondary schools and in certain community settings, under current tracing levels, 68% or 46% of those with symptomatic infection would need to be tested if masks effective coverage were 15% or 30% respectively, compared to 76% and 57% if masks are mandated in community settings but not secondary schools.

Determining the optimal strategy for reopening schools, work and society in the UK: balancing earlier opening and the impact of test and trace strategies with the risk of occurrence of a secondary COVID-19 pandemic wave

BackgroundIn order to slow down the spread of SARS-CoV-2, the virus causing the COVID-19 pandemic, the UK government has imposed strict physical distancing ( lockdown) measures including school dismissals since 23 March 2020. As evidence is emerging that these measures may have slowed the spread of the pandemic, it is important to assess the impact of any changes in strategy, including scenarios for school reopening and broader relaxation of social distancing. This work uses an individual-based model to predict the impact of a suite of possible strategies to reopen schools in the UK, including that currently proposed by the UK government. MethodsWe use Covasim, a stochastic agent-based model for transmission of COVID-19, calibrated to the UK epidemic. The model describes individuals contact networks stratified as household, school, work and community layers, and uses demographic and epidemiological data from the UK. We simulate a range of different school reopening strategies with a society-wide relaxation of lockdown measures and in the presence of different non-pharmaceutical interventions, to estimate the number of new infections, cumulative cases and deaths, as well as the effective reproduction number with different strategies. To account for uncertainties within the stochastic simulation, we also simulated different levels of infectiousness of children and young adults under 20 years old compared to older ages. FindingsWe found that with increased levels of testing of people (between 25% and 72% of symptomatic people tested at some point during an active COVID-19 infection depending on scenarios) and effective contact-tracing and isolation for infected individuals, an epidemic rebound may be prevented across all reopening scenarios, with the effective reproduction number (R) remaining below one and the cumulative number of new infections and deaths significantly lower than they would be if testing did not increase. If UK schools reopen in phases from June 2020, prevention of a second wave would require testing 51% of symptomatic infections, tracing of 40% of their contacts, and isolation of symptomatic and diagnosed cases. However, without such measures, reopening of schools together with gradual relaxing of the lockdown measures are likely to induce a secondary pandemic wave, as are other scenarios for reopening. When infectiousness of <20 year olds was varied from 100% to 50% of that of older ages, our findings remained unchanged. InterpretationTo prevent a secondary COVID-19 wave, relaxation of social distancing including reopening schools in the UK must be implemented alongside an active large-scale population-wide testing of symptomatic individuals and effective tracing of their contacts, followed by isolation of symptomatic and diagnosed individuals. Such combined measures have a greater likelihood of controlling the transmission of SARS-CoV-2 and preventing a large number of COVID-19 deaths than reopening schools and society with the current level of implementation of testing and isolation of infected individuals. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSSince the onset of COVID-19 pandemic, mathematical modelling has been at the heart of informing decision-making, including the imposing of the lockdown in the UK. As countries are now starting to plan modification of these measures, it is important to assess the impact of different lockdown exit strategies including whether and how to reopen schools and relax other social distancing measures. Added value of this studyUsing mathematical modelling, we explored the impact of strategies to reopen schools and society in the UK, including that currently proposed by the UK government. We assessed the impact of opening all schools fully or in a phased way with only some school years going back, with a society-wide relaxation of lockdown measures and in the presence of a different levels of implementation of test-trace-isolate strategies. We projected the number of new COVID-19 infections, cumulative cases and deaths, as well as the temporal distribution in the effective reproduction number (R) across different strategies. Our study is the first to provide quantification of the amount of testing and tracing that would be needed to prevent a second wave of COVID-19 in the UK under different reopening scenarios. To account for uncertainties within the stochastic simulation, we also simulated different levels of infectiousness of children and young adults under 20 years old compared to older ages. Implications of all the available evidenceEvidence to date points to the need for additional testing, contact tracing, and isolation of individuals who have either been diagnosed with COVID-19, or who are considered to be at high risk of carrying infection due to their contact history or symptoms. Our study supports these conclusions and provides additional quantification of the amount of testing and tracing that would be needed to prevent a second wave of COVID-19 in the UK under different lockdown exit strategies. Reopening schools and society alongside active testing of the symptomatic population (between 25% and 72% of people with symptomatic COVID-19 infection depending on scenarios) and with an effective contact-tracing and rapid isolation of symptomatic and diagnosed individuals, will not only prevent a secondary pandemic wave, but is also likely to be able to control the transmission of SARS-CoV-2, via keeping the R value below 1, thus preventing a large number of COVID-19 cases and deaths. However, in the absence of fully implemented large-scale testing, contact-tracing and isolation strategy, plans for reopening schools, including those currently proposed by the UK government, and the associated increase in work and community contacts, are likely to induce a secondary pandemic wave of COVID-19.

Susceptibility to and transmission of COVID-19 amongst children and adolescents compared with adults: a systematic review and meta-analysis

ImportanceThe degree to which children and young people are infected by and transmit the SARS-CoV-2 virus is unclear. The role of children and young people in transmission of SARS-CoV-2 is dependent on susceptibility, symptoms, viral load, social contact patterns and behaviour. ObjectiveWe undertook a rapid systematic review to address the question "What is the susceptibility to and transmission of SARS-CoV-2 by children and adolescents compared with adults?" Data sourcesWe searched PubMed and medRxiv up to 28 July 2020 and identified 13,926 studies, with additional studies identified through handsearching of cited references and professional contacts. Study SelectionWe included studies which provided data on the prevalence of SARS-CoV-2 in children and young people (<20 years) compared with adults derived from contact-tracing or population-screening. We excluded single household studies. Data extraction and SynthesisWe followed PRISMA guidelines for abstracting data, independently by 2 reviewers. Quality was assessed using a critical appraisal checklist for prevalence studies. Random effects meta-analysis was undertaken. Main OutcomesSecondary infection rate (contact-tracing studies) or prevalence or seroprevalence (population-screening studies) amongst children and young people compared with adults. Results32 studies met inclusion criteria; 18 contact-tracing and 14 population-screening. The pooled odds ratio of being an infected contact in children compared with adults was 0.56 (0.37, 0.85) with substantial heterogeneity (95%). Three school contact tracing studies found minimal transmission by child or teacher index cases. Findings from population-screening studies were heterogenous and were not suitable for meta-analysis. The majority of studies were consistent with lower seroprevalence in children compared with adults, although seroprevalence in adolescents appeared similar to adults. ConclusionsThere is preliminary evidence that children and young people have lower susceptibility to SARS-CoV-2, with a 43% lower odds of being an infected contact. There is weak evidence that children and young people play a lesser role in transmission of SARS-CoV-2 at a population level. Our study provides no information on the infectivity of children. Key pointsO_ST_ABSQuestionC_ST_ABSWhat is the evidence on the susceptibility and transmission of children and young people to SARS-CoV-2 in comparison with adults? FindingsIn this systematic review and meta-analysis, children and young people under 18-20 years had an 435 lower odds of secondary infection of with SARS-CoV-2 compared to adults 20 years plus, a significant difference. This finding was most marked in children under 12-14 years. Data were insufficient to conclude whether transmission of SARS-CoV-2 by children is lower than by adults. MeaningWe found preliminary evidence that children have a lower susceptibility for SARS-CoV-2 infection compared with adults, although data for adolescents is less clear. The role that children and young people play in transmission of this pandemic remains unclear.