Paediatric critical COVID-19 and mortality in a multinational prospective cohort.

Background: To understand critical paediatric coronavirus disease 2019 (COVID-19) and evaluate factors associated with mortality in children from high and low-middle income countries. Methods: Prospective, observational study of critically ill children hospitalised for COVID-19 in 18 countries throughout North America, Latin America, and Europe between April 1 and December 31, 2020. Associations with mortality were evaluated using logistic regression. Findings: 557 patients (median age, 8 years; 24% <2 years) were enrolled from 55 sites (63% Latin American). Half had comorbidities. Invasive (41%) or non-invasive (20%) ventilation and vasopressors (56%) were the most common support modalities. Hospital mortality was 10% and higher in children <2 years old (15%; odds ratio 1·94, 95%CI 1·08-3·49). Most who died had pulmonary disease. When adjusted for age, sex, region, and illness severity, mortality-associated factors included cardiac (aOR 2·89; 95%CI 1·2-6·94) or pulmonary comorbidities (aOR 4·43; 95%CI 1·70-11·5), admission hypoxemia (aOR 2·44; 95%CI 1·30-4·57), and lower respiratory symptoms (aOR 2·96; 95%CI 1·57-5·59). MIS-C (aOR 0·25; 95%CI 0·1-0·61) and receiving methylprednisolone (aOR 0·5; 95%CI 0·25-0·99), IVIG (aOR 0·32; 95%CI 0·16-0·62), or anticoagulation (aOR 0·49; 95%CI 0·25-0·95) were associated with lower mortality although these associations might be limited to children >2 years old. Interpretation: We identified factors associated with COVID-19 mortality in critically ill children from both high and low-middle income countries, including higher mortality with younger age and COVID-related pulmonary disease but lower mortality in MIS-C. Further research is needed on optimal treatments for younger children and respiratory failure in paediatric COVID-19. Funding: None.

Effect of sedation with inhaled anaesthetics on cognitive and psychiatric outcomes in critically ill adults: a systematic review protocol.

INTRODUCTION: The COVID-19 pandemic has renewed interest in the use of inhaled anaesthetics for sedation of ventilated critically ill patients. Preliminary data show that inhaled anaesthetics reduce lung inflammation, time to extubation and intensive care unit length of stay compared with intravenous sedatives. However, the impact of inhaled anaesthetics on cognitive and psychiatric outcomes is not well described in this setting. Randomised controlled trials are underway to establish if inhaled anaesthetics affect these and other patient and health system outcomes. Our aim is to summarise the known effects of inhaled sedatives on cognitive and psychiatric outcomes. METHODS AND ANALYSIS: In this systematic review, we will use MEDLINE, EMBASE, and PsycINFO to identify studies from 1970 to 2021 that assessed cognitive and psychiatric outcomes in critically ill adult patients sedated with inhaled anaesthetics. We will include case series, observational and cohort studies and randomised controlled trials. We will exclude case studies due to the heterogeneity of reporting in these studies. For randomised controlled trials comparing inhaled to intravenous sedation, we will report cognitive and psychiatric outcomes for both study arms. Studies will be selected based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Data will be extracted using a standardised data extraction tool by two independent reviewers. Studies will be assessed for bias using the Cochrane risk of bias tool for randomised controlled trials, or the Newcastle-Ottawa Scale for cohort and case-control studies. Findings will be reported according to outcome and descriptive statistics will be used to illustrate findings in a narrative fashion. ETHICS AND DISSEMINATION: The systematic review uses published data and therefore does not require ethics approval. Results will be disseminated via publication in peer-reviewed journals and presentation at conferences related to the field. PROSPERO REGISTRATION NUMBER: CRD42021236455.

Prevalence and Risk Factors of Neurologic Manifestations in Hospitalized Children Diagnosed with Acute SARS-CoV-2 or MIS-C.

BACKGROUND: Our objective was to characterize the frequency, early impact, and risk factors for neurological manifestations in hospitalized children with acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or multisystem inflammatory syndrome in children (MIS-C). METHODS: Multicenter, cross-sectional study of neurological manifestations in children aged <18 years hospitalized with positive SARS-CoV-2 test or clinical diagnosis of a SARS-CoV-2-related condition between January 2020 and April 2021. Multivariable logistic regression to identify risk factors for neurological manifestations was performed. RESULTS: Of 1493 children, 1278 (86%) were diagnosed with acute SARS-CoV-2 and 215 (14%) with MIS-C. Overall, 44% of the cohort (40% acute SARS-CoV-2 and 66% MIS-C) had at least one neurological manifestation. The most common neurological findings in children with acute SARS-CoV-2 and MIS-C diagnosis were headache (16% and 47%) and acute encephalopathy (15% and 22%), both P < 0.05. Children with neurological manifestations were more likely to require intensive care unit (ICU) care (51% vs 22%), P < 0.001. In multivariable logistic regression, children with neurological manifestations were older (odds ratio [OR] 1.1 and 95% confidence interval [CI] 1.07 to 1.13) and more likely to have MIS-C versus acute SARS-CoV-2 (OR 2.16, 95% CI 1.45 to 3.24), pre-existing neurological and metabolic conditions (OR 3.48, 95% CI 2.37 to 5.15; and OR 1.65, 95% CI 1.04 to 2.66, respectively), and pharyngeal (OR 1.74, 95% CI 1.16 to 2.64) or abdominal pain (OR 1.43, 95% CI 1.03 to 2.00); all P < 0.05. CONCLUSIONS: In this multicenter study, 44% of children hospitalized with SARS-CoV-2-related conditions experienced neurological manifestations, which were associated with ICU admission and pre-existing neurological condition. Posthospital assessment for, and support of, functional impairment and neuroprotective strategies are vitally needed.