Prognostic factors for mortality, ICU, MIS-C and hospital admission due to SARS-CoV-2 in paediatric patients: A systematic review and meta-analysis (preprint)

ABSTRACT Background: There is a paucity of data on the factors associated with severe COVID-19 disease, especially in children. This systematic review and meta-analysis aim to identify the risk factors for acute adverse outcomes of COVID-19 within paediatric populations, using the recruitment setting as a proxy of initial disease severity. Methods: A systematic review and meta-analysis were performed representing published evidence from the start of the pandemic up to 14 February 2022. Our primary outcome was the identification of risk factors for adverse outcomes, stratified by recruitment setting (community, hospital). No geographical restrictions were imposed. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to evaluate the certainty in the body of evidence for each meta-analysis. In anticipation of significant clinical and methodological heterogeneity in the meta-analyses, we fitted logistic regression models with random effects. Findings: Our review identified 47 studies involving 94,210 paediatric cases of COVID-19. Infants up to 3 months were more likely to be hospitalised than older children. Gender and ethnicity were not associated with an increased likelihood of adverse outcomes among children within the community setting. Concerning comorbidities, having at least one pre-existing disease increased the odds of hospitalisation. Concerning BMI, underweight children and severely obese were noted to have an increased likelihood of hospital admission. The presence of metabolic disorders and children with underlying cardiovascular diseases, respiratory disorders, neuromuscular disorders and neurologic conditions were also more likely to be hospitalised. Concerning underlying comorbidities, paediatric hospitalised patients with congenital/genetic disease, those obese, with malignancy, cardiovascular diseases and respiratory disease were associated with higher odds of being admitted to ICU or ventilated. Interpretation: Our findings suggest that age, male, gender, and paediatric comorbidities increased the likelihood of hospital and ICU admission. Obesity, malignancy, and respiratory and cardiovascular disorders were among the most important risk factors for hospital and ICU admission among children with COVID-19. The extent to which these factors were linked to actual severity or where the application of cautious preventive care is an area in which further research is needed.

Effectiveness of non-pharmaceutical interventions on SARS-CoV-2 transmission during the period January 2021 until May 2022: A systematic literature review (preprint)

ObjectivesIn response to the COVID-19 pandemic, countries implemented various non-pharmaceutical interventions(NPIs). With this systematic review, we investigated the effectiveness of NPIs in mitigating SARS-CoV-2 transmission by assessing empirical evidence and data obtained through modelling studies. DesignWe searched Medline(OVID) and EMBASE until 26 May 2022. The PICO framework was used to determine the eligibility of the studies. Populations were restricted to studies on humans, and there was no geographical limitation. The included articles assessed NPIs at the regional or national level as mitigation measures against SARS-CoV-2 transmission for human population without geographical limitation. Unmitigated SARS-CoV-2 transmission or the period before the implementation of the assessed NPI were used as the comparator. Main outcome measuresOutcome indicators were extracted and included COVID-19 cases, incidence and peaks, reproduction rate, growth rate, case mortality, and hospital and Intensive Care Unit admissions. Due to the heterogeneity between studies, statistical analysis was not possible and hence the results were presented narratively. Results49 studies were included; 21 based on empirical evidence and 28 modelling studies. Among the latter, the effectiveness of facemasks was evaluated in 11 studies, five assessed stay-at-home orders and five school closures. Regarding face mask use, the majority of studies presented a beneficial effect when appropriate social distancing measures could not be maintained. Restrictions on mass gatherings, stay-at-home-orders and lockdown measures were found to be effective in reducing SARS-CoV-2 transmission when timely and properly implemented. The results related to school closures were inconclusive. ConclusionsThis systematic review assesses the effectiveness of NPIs in reducing SARS-CoV-2 transmission from January 2021 until May 2022. It suggests the importance of timely implementation and the optimised impact when implementing multiple NPIs in parallel. Continuous monitoring of the effectiveness of NPIs is required to determine the most suitable nature, time, and duration of the implemented NPIs. What is already known on this topicPrior to this study, it was recognised that in response to the COVID-19 pandemic, various non-pharmaceutical interventions (NPIs) such as hygiene measures, face mask usage, travel restrictions, social distancing, and contact tracing were implemented worldwide. The scientific community has been assessing the effectiveness of these NPIs in mitigating the pandemics impact on public health and the economy. What this study addsThis systematic review contributes by presenting updated and comprehensive evidence regarding the effectiveness of NPIs as a means of mitigating SARS-CoV-2 transmission, using both real-world evidence and data obtained through modelling studies. The study affirms that the timely application of NPIs, including the use of face masks, stay-at-home orders, restrictions on mass gatherings, and school closures, substantially reduced COVID-19 cases and fatalities. It underscores the significance of employing multiple NPIs in tandem for heightened effectiveness within future respiratory pandemics. The review emphasises the necessity for ongoing assessment of NPI efficacy, taking into account factors such as public compliance, vaccination rates, and the prevalence of virus variants. How this study might affect research, practice, or policyThe findings of this study carry various implications. Firstly, they inform policymakers about the critical importance of promptly implementing NPIs and employing them in combination to manage respiratory pandemics. Secondly, the results underscore the enduring relevance of NPIs even as pandemic vaccination campaigns progress. Thirdly, the study highlights the need for standardized methodologies for evaluating the effectiveness of NPIs. Lastly, this review can guide future public health strategies by offering valuable insights into the impact of different interventions on pandemic control.

A systematic review on outbreaks of COVID-19 among children within households in the European region (preprint)

Objectives: This systematic review aims to identify the secondary attack rates (SAR) to adults and other children when children are the index cases within household settings. Methods: This literature review assessed European-based studies published in Medline and Embase between January 2020 and January 2022 that assessed the secondary transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within household settings. The inclusion criteria were based on the PEO framework (P-Population, E-Exposure, O-Outcome) for systematic reviews. Thus, the study population was restricted to humans within the household setting in Europe (population), in contact with pediatric index cases 1 to 17 years old (exposure) that led to the transmission of SARS-CoV-2 reported as either a SAR or the probability of onward infection (outcome). Results: Of 1,819 studies originally identified, 25 met the inclusion criteria. Overall, the SAR ranged from 13% to 75% in 23 studies, while there was no evidence of secondary transmission from children to other household members in two studies. Evidence indicated that asymptomatic SARS-CoV-2 index cases also have a lower SAR than those with symptoms and that younger children may have a lower SAR than adolescents (>12 years old) within household settings. Conclusions: SARS-CoV-2 secondary transmission from paediatric index cases ranged from 0% to 75%, within household settings between January 2020 and January 2022, with differences noted by age and by symptomatic/asymptomatic status of the index case. Given the anticipated endemic circulation of SARS-CoV-2, continued monitoring and assessment of household transmission is necessary.

The cost of the COVID-19 pandemic vs the cost-effectiveness of mitigation strategies in the EU/UK/EEA and OECD countries: a systematic review (preprint)

ABSTRACT Objectives COVID-19 poses a threat of loss of life, economic instability, and social disruption. We conducted a systematic review of published economic analyses to assess the direct and indirect costs of the SARS-CoV-2 pandemic, and to contrast these with the costs and the cost-benefit of public health surveillance, preparedness, and response measures in averting and/or responding to SARS-CoV-2 pandemic. Setting A systematic literature review was conducted to identify peer-reviewed articles estimating the cost of the COVID-19 pandemic and the cost-effectiveness of pharmaceutical or non-pharmaceutical interventions in EU/EEA/UK and OECD countries, published from the 1st of January 2020 through 22nd April 2021 in Ovid Medline and EMBASE. The cost-effectiveness of interventions was assessed through a dominance ranking matrix approach. All cost data were adjusted to the 2021 Euro, with interventions compared with the null. Primary and secondary outcome measures Direct and indirect costs for SARS-CoV-2 and preparedness and/or response or cost-benefit and cost-effectiveness were measured. Results We included data from 41 economic studies. Ten studies evaluated the cost of COVID-19 pandemic, while 31 assessed the cost-benefit of public health surveillance, preparedness, and response measures. Overall, the economic burden of SARS-CoV-2 was found to be substantial for both the general population and within specific population subgroups. Community screening, bed provision policies, investing in personal protective equipment and vaccination strategies were cost-effective, in most cases due to the representative economic value of below acceptable cost-effectiveness thresholds. Physical distancing measures were associated with health benefits; however, their cost-effectiveness was dependent on the duration, compliance and the phase of the epidemic in which it was implemented. Conclusions SARS-CoV-2 is associated with substantial economic costs to healthcare systems, payers, and societies, both short term and long term, while interventions including testing and screening policies, vaccination and physical distancing policies were identified as those presenting cost-effective options to deal with the pandemic, dependent on population vaccination and the Re at the stage of the pandemic.

Prognostic factors for mortality, ICU and hospital admission due to SARS-CoV-2: A systematic review and meta-analysis of cohort studies in Europe (preprint)

BackgroundAs mortality from COVID-19 is strongly age-dependent, we aimed to identify population subgroups at an elevated risk for adverse outcomes from COVID-19 using age/gender-adjusted data from European cohort studies with the aim to identify populations that could potentially benefit from booster vaccinations. MethodsWe performed a systematic literature review and meta-analysis to investigate the role of underlying medical conditions as prognostic factors for adverse outcomes due to SARS-CoV-2, including death, hospitalisation, Intensive Care Unit (ICU) admission, and mechanical ventilation within three separate settings (community, hospital and ICU). Cohort studies that reported at least age and gender-adjusted data from Europe were identified through a search of peer-reviewed articles published until 11th June 2021 in Ovid Medline and Embase. Results are presented as Odds Ratios (ORs) with 95% confidence intervals (95%C.I.) and absolute risk differences (RD) in deaths per 1,000 COVID-19 patients. FindingsWe included 88 cohort studies with age/gender adjusted data from 6,653,207 SARS-CoV-2 patients from Europe. Hospital-based mortality was associated with high and moderate certainty evidence for solid organ tumours, diabetes mellitus, renal disease, arrhythmia, ischemic heart disease, liver disease, and obesity, while a higher risk, albeit with low certainty, was noted for chronic obstructive pulmonary disease and heart failure. Community-based mortality was associated with a history of heart failure, stroke, diabetes, and end-stage renal disease. Evidence of high/moderate certainty revealed a strong association between hospitalisation for COVID-19 and solid organ transplant recipients, sleep apnoea, diabetes, stroke, and liver disease. InterpretationThe results confirmed the strong association between specific prognostic factors and mortality and hospital admission. Prioritisation of booster vaccinations and the implementation of non-pharmaceutical protective measures for these populations may contribute to a reduction in COVID-19 mortality, ICU and hospital admissions. FundingEuropean Centre for Disease Prevention and Control (ECDC) under specific contract No. 10 ECD.11843 within Framework contract ECDC/2019/001 Lot 1B.

Effectiveness of non-pharmaceutical measures (NPIs) on COVID-19 in Europe: A systematic literature review (preprint)

Background The study objective was to conduct a systematic review to assess the effectiveness of non-pharmaceutical interventions (NPIs) to reduce the transmission of SARS-CoV-2 in Europe during the first wave of the pandemic. Methods We searched OVID Medline, EMBASE, and the Cochrane and Campbell Databases for Systematic Reviews published up to April 15 th 2021. Focusing on community (meso-level) and society (macro-level) level NPIs, we included all study designs, while a geographic restriction was limited to the EU, UK and European Economic Area (EEA) countries. Using the PICO framework, two reviewers independently extracted data and assessed quality using appropriate quality appraisal tools. A qualitative synthesis was performed, with NPIs grouped initially by a) Physical Distancing measures, b) Case detection and management measures, and c) hygiene measures and subsequently by country. Results Of 17,692 studies initially assessed, 45 met all inclusion criteria. Most studies (n=30) had a modelling study design, while 13 were observational, one quasi-experimental and one experimental. Evidence from across the European continent, presented by country, indicates that the implementations of physical distancing measures (i.e., lockdowns/quarantines), preferably earlier in the pandemic, reduce the number of cases and hospitalisation across settings and for which the timing and duration are essential parameters. Case detection and management measures were also identified as effective measures at certain levels of testing and incidence, while hygiene and safety measures complemented the implementation of physical distancing measures. Conclusions This literature review represents a comprehensive assessment of the effectiveness of NPIs in Europe up to April 2021. Despite heterogeneity across studies, NPIs, as assessed within the context of this systematic review at the macro and meso level, are effective in reducing SARS-CoV-2 transmission rates and COVID-19 hospitalisation rates and deaths in the European Region and may be applied as response strategies to reduce the burden of COVID-19 in forthcoming waves.

The role of educational settings in the transmission chain of SARS-CoV-2 in 2020: a systematic review (preprint)

BackgroundSchool closures have been used as a core Non pharmaceutical intervention during the COVID-19 pandemic, however the role of educational settings in COVID-19 transmission is still unclear. MethodsThis systematic literature review assessed studies published between December 2019 and April 1, 2021 in Medline and Embase, which included studies that assessed educational settings from approximately January 2020 to January 2021. The inclusion criteria were based on the PCC framework (P-Population, C-Concept, C-Context). The study Population was restricted to people 1-17 years old (excluding neonatal transmission), the Concept was to assess child-to-child and child-to-adult transmission, while the Context was to assess specifically educational setting transmission clusters. ResultsFifteen studies met inclusion criteria, ranging from daycare centers to high schools and summer camps, while eight studies assessed the re-opening of schools in the 2020-2021 school year. In principle although there is sufficient evidence that children can both be infected by and transmit SARS-CoV-2 in school settings, the SAR remain relatively low -when NPI measures are implemented in parallel. Moreover, although the evidence was limited there was an indication that younger children may have a lower SAR than adolescents. ConclusionsTransmission in educational settings in 2020 was minimal -when NPI measures were implemented in parallel. However, with an upsurge of cases related to variants of concern, continuous surveillance and assessment of the evidence is warranted to ensure the maximum protection of the health of students and the educational workforce, while also minimising the numerous negative impacts that school closures may have on children. Strengths and limitations of this studyO_LIThis study provides a rapid review of the peer-reviewed literature pertaining to SARS-CoV-2 transmission by children within educational settings. C_LIO_LIThe review reflects the status quo of the previous school years (January 2020 -January 2021) due to the lag time between study implementation, peer review and publication. C_LIO_LIThe included studies represent child-to-child transmission within the context of previous SARS-CoV-2 strains and are not directly applicable to newer variants. C_LI

The role of children in the transmission chain of SARS-CoV-2: a systematic review and update of current evidence (preprint)

Decisions on school closures and on safe schooling during the COVID-19 pandemic should be evidence-based. We conducted a systematic literature review to assess child-to-child and child-to-adult SARS-CoV-2 transmission and to characterise the potential role of school closures on community transmission. 1337 peer-reviewed articles published through August 31, 2020 were screened; 22 were included in this review. The literature appraised provides sufficient evidence that children can both be infected by and transmit SARS-CoV-2 in community, household and school settings. Transmission by children was most frequently documented in household settings, while examples of children as index cases in school settings were rare. Included studies suggested that school closures may help to reduce SARS-CoV-2 transmission, but the societal, economic, and educational impacts of prolonged school closures must be considered. In-school mitigation measures, alongside continuous surveillance and assessment of emerging evidence, will promote the protection and educational attainment of students and support the educational workforce.