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.

Risk of hospitalization and risk of death for healthcare workers with COVID-19 in nine European Union/European Economic Area countries, January 2020 - January 2021 (preprint)

We assessed the impact of COVID-19 on healthcare workers (HCWs) from data on 2.9 million cases reported from nine countries in the EU/EEA. Compared to non-HCWs, HCWs had a higher adjusted risk of hospitalization (IRR 3.0 [95% CI 2.2-4.0]), but not death (IRR 0.9, 95% CI 0.4-2.0). Article Summary LineHealthcare workers are hospitalized more frequently than non-healthcare workers when adjusting for age, sex, and comorbidities.