Neurological manifestations of COVID-19 in adults and children

Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P < 0.001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age

The BCL2-938 C > A promoter polymorphism is associated with risk group classification in children with acute lymphoblastic leukemia

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. While current treatment regimens achieve almost 80% overall survival, long-term side effects of chemotherapeutic agents can be severe. The functional BCL2-938C > A promoter polymorphism is known to influence the balance between survival and apoptosis of malignant hematolymphoid cells. We investigated its usefulness as a marker for treatment stratification for children with ALL. METHODS: We analyzed DNA from 182 children suffering from ALL in this study to determine genotypes of the−938 C > A polymorphism by “slow-down” PCR. RESULTS: ALL patients with the BCL2-938CC genotype had an approximately 3-fold higher risk of belonging to a high-risk group. Within the high-risk group, 50% of BCL2-938CC patients were classified as high-risk due to poor prednisone response whereas only 33% of patients with AC and AA genotypes were classified as high-risk for the same reason. CONCLUSIONS: Our results suggest that BCL2-938C > A genotyping may be beneficial for therapy response prediction in ALL patients, and warrant examination in a larger cohort to validate its usefulness for treatment stratification of pediatric ALL patients

Septic Shock in Children in an Urban Area in Western Germany - Outcome, Risk Factors for Mortality and Infection Epidemiology

Background: Only sparse data exist about children with septic shock in Europe. The present study aimed to evaluate demographics, treatment, outcome and risk factors for mortality in Western Germany. Patients: Children with septic shock aged 2 months to 17 years. Methods: In a multi-center retrospective study of 20 children's hospitals data were obtained and analyzed by chart review. Risk factors for mortality were identified and assessed by multivariate regression analysis. Results: Overall mortality in 83 cases with septic shock was 25 % (21 patients). Significant risk factors were high PRISM III score, low pH, low arterial systolic blood pressure, presence of disseminated intravascular coagulation and extent of multi-organ failure, but not lactate (p = 0.05) and base excess (p = 0.065). Mortality in hospitals which treated 10 or more patients (category 1) was 17 % and increased to 22 % in hospitals which treated 3-6 patients (category 2). In hospitals with only 1 or 2 patients (category 3) mortality rate was 61 % (p 19): category 1: 23 %, category 2: 40 %, category 3: 62.5 % (p < 0.05 for comparison of category 1 and 3). Multivariate analysis of significant risk factors revealed low number of treated patients as the only individual risk factor for mortality. Conclusion: Mortality from pediatric septic shock in an urban area in Western Germany is high. Disease severity and treatment in a department with few cases were associated with increased mortality

Prevalence of Errors in Anaphylaxis in Kids (PEAK): A Multicenter Simulation-Based Study

Multi-institutional, international practice variation of pediatric anaphylaxis management by health care providers has not been reported. To characterize variability in epinephrine administration for pediatric anaphylaxis across institutions, including frequency and types of medication errors. A prospective, observational, study using a standardized in situ simulated anaphylaxis scenario was performed across 28 health care institutions in 6 countries. The on-duty health care team was called for a child (patient simulator) in anaphylaxis. Real medications and supplies were obtained from their actual locations. Demographic data about team members, institutional protocols for anaphylaxis, timing of epinephrine delivery, medication errors, and systems safety issues discovered during the simulation were collected. Thirty-seven in situ simulations were performed. Anaphylaxis guidelines existed in 41% (15 of 37) of institutions. Teams used a cognitive aid for medication dosing 41% (15 of 37) of the time and 32% (12 of 37) for preparation. Epinephrine autoinjectors were not available in 54% (20 of 37) of institutions and were used in only 14% (5 of 37) of simulations. Median time to epinephrine administration was 95 seconds (interquartile range, 77-252) for epinephrine autoinjector and 263 seconds (interquartile range, 146-407.5) for manually prepared epinephrine (P = .12). At least 1 medication error occurred in 68% (25 of 37) of simulations. Nursing experience with epinephrine administration for anaphylaxis was associated with fewer preparation (P = .04) and administration (P = .01) errors. Latent safety threats were reported by 30% (11 of 37) of institutions, and more than half of these (6 of 11) involved a cognitive aid. A multicenter, international study of simulated pediatric anaphylaxis reveals (1) variation in management between institutions in the use of protocols, cognitive aids, and medication formularies, (2) frequent errors involving epinephrine, and (3) latent safety threats related to cognitive aids among multiple sites

An international observational study to assess the impact of the Omicron variant emergence on the clinical epidemiology of COVID-19 in hospitalised patients

Background: Whilst timely clinical characterisation of infections caused by novel SARS-CoV-2 variants is necessary for evidence-based policy response, individual-level data on infecting variants are typically only available for a minority of patients and settings. Methods: Here, we propose an innovative approach to study changes in COVID-19 hospital presentation and outcomes after the Omicron variant emergence using publicly available population-level data on variant relative frequency to infer SARS-CoV-2 variants likely responsible for clinical cases. We apply this method to data collected by a large international clinical consortium before and after the emergence of the Omicron variant in different countries. Results: Our analysis, that includes more than 100,000 patients from 28 countries, suggests that in many settings patients hospitalised with Omicron variant infection less often presented with commonly reported symptoms compared to patients infected with pre-Omicron variants. Patients with COVID-19 admitted to hospital after Omicron variant emergence had lower mortality compared to patients admitted during the period when Omicron variant was responsible for only a minority of infections (odds ratio in a mixed-effects logistic regression adjusted for likely confounders, 0.67 [95% confidence interval 0.61-0.75]). Qualitatively similar findings were observed in sensitivity analyses with different assumptions on population-level Omicron variant relative frequencies, and in analyses using available individual-level data on infecting variant for a subset of the study population. Conclusions: Although clinical studies with matching viral genomic information should remain a priority, our approach combining publicly available data on variant frequency and a multi-country clinical characterisation dataset with more than 100,000 records allowed analysis of data from a wide range of settings and novel insights on real-world heterogeneity of COVID-19 presentation and clinical outcome

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

International audienceAbstract Background The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men