Respiratory and nonrespiratory COVID-19 complications in patients with obesity: recent developments.

This narrative review summarizes recent reports to provide an updated understanding of the multiorgan effects of SARS-CoV-2 infection in obese individuals. A PubMed search of 528 primary articles was performed, with inclusion based on novelty, relevance and redundancy. Obesity confers an increased risk for hospitalization, intensive care unit admission, severe pneumonia, intubation and acute kidney injury in COVID-19 patients. Obesity is also associated with higher levels of inflammatory and thrombotic markers. However, the associations between obesity and mortality or cardiac injury in COVID-19 patients remain unclear. Obesity is a risk factor for several respiratory and nonrespiratory COVID-19 complications. Future work is needed to further explore these relationships and optimize the management of obese COVID-19 patients.

The dopamine receptor agonist apomorphine stabilizes neurotoxic α-synuclein oligomers.

The misfolding and aggregation of the protein α-synuclein (aSyn) into potentially neurotoxic oligomers is believed to play a pivotal role in the neuropathogenesis of Parkinson's disease (PD). Herein, we explore how apomorphine (Apo), a nonselective dopamine D1 and D2 receptor agonist utilized in the therapy for PD, affects the aggregation and toxicity of aSyn in vitro. Our data indicated that Apo inhibits aSyn fibrillation leading to the formation of large oligomeric species (Apo-aSyn-O), which exhibit remarkable toxicity in mesencephalic dopaminergic neurons in primary cultures. Interestingly, purified Apo-aSyn-O, even at very low concentrations, seems to be capable of converting unmodified aSyn monomer into neurotoxic species. Collectively, our findings warn for a possible dangerous effect of Apo on aSyn misfolding/aggregation pathway.

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.

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.

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.

Extracellular matrix-derived biomaterials in engineering cell function.

Extracellular matrix (ECM) derived components are emerging sources for the engineering of biomaterials that are capable of inducing desirable cell-specific responses. This review explores the use of biomaterials derived from naturally occurring ECM proteins and their derivatives in approaches that aim to regulate cell function. Biomaterials addressed are grouped into six categories: purified single ECM proteins, combinations of purified ECM proteins, cell-derived ECM, tissue-derived ECM, diseased and modified ECM, and ECM-polymer coupled biomaterials. Purified ECM proteins serve as a material coating for enhanced cell adhesion and biocompatibility. Cell-derived and tissue-derived ECM, generated by cell isolation and decellularization technologies, can capture the native state of the ECM environment and guide cell migration and alignment patterns as well as stem cell differentiation. We focus primarily on recent advances in the fields of soft tissue, cardiac, and dermal repair, and explore the utilization of ECM proteins as biomaterials to engineer cell responses.

Tunable Hydrogels Derived from Genetically Engineered Extracellular Matrix Accelerate Diabetic Wound Healing.

Hydrogels composed of solubilized decellularized extracellular matrix (ECM) are attractive materials because they combine the complexity of native ECM with injectability and ease of use. Nevertheless, these materials are typically only tunable by altering the concentration, which alters the ligand landscape, or by incorporating synthetic components, which can result in an unfavorable host response. Herein, we demonstrate the fabrication of genetically tunable ECM-derived materials, by utilizing wild type (WT) and (thrombospondin-2 knockout) TSP-2 KO decellularized skins to prepare hydrogels. The resulting materials exhibited distinct mechanical properties characterized by rheology and different concentrations of collagens when characterized by quantitative proteomics. Mixtures of the gels achieved intermediate effects between the WT and the KO, permitting tunability of the gel properties. In vivo, the hydrogels exhibited tunable cell invasion with a correlation between the content of TSP-2 KO hydrogel and the extent of cell invasion. Additionally, TSP-2 KO hydrogels significantly improved diabetic wound healing at 10 and 21 days. Furthermore, hydrogels derived from genetically engineered in vitro cell-derived matrix mimicked the trends observed for tissue-derived matrix, providing a platform for faster screening of novel manipulations and easier clinical translation. Overall, we demonstrate that genetic engineering approaches impart tunability to ECM-based hydrogels and can result in materials capable of enhanced regeneration.