Multinational characterization of neurological phenotypes in patients hospitalized with COVID-19

Neurological complications worsen outcomes in COVID-19. To define the prevalence of neurological conditions among hospitalized patients with a positive SARS-CoV-2 reverse transcription polymerase chain reaction test in geographically diverse multinational populations during early pandemic, we used electronic health records (EHR) from 338 participating hospitals across 6 countries and 3 continents (January–September 2020) for a cross-sectional analysis. We assessed the frequency of International Classification of Disease code of neurological conditions by countries, healthcare systems, time before and after admission for COVID-19 and COVID-19 severity. Among 35,177 hospitalized patients with SARS-CoV-2 infection, there was an increase in the proportion with disorders of consciousness (5.8%, 95% confidence interval [CI] 3.7–7.8%, pFDR < 0.001) and unspecified disorders of the brain (8.1%, 5.7–10.5%, pFDR < 0.001) when compared to the pre-admission proportion. During hospitalization, the relative risk of disorders of consciousness (22%, 19–25%), cerebrovascular diseases (24%, 13–35%), nontraumatic intracranial hemorrhage (34%, 20–50%), encephalitis and/or myelitis (37%, 17–60%) and myopathy (72%, 67–77%) were higher for patients with severe COVID-19 when compared to those who never experienced severe COVID-19. Leveraging a multinational network to capture standardized EHR data, we highlighted the increased prevalence of central and peripheral neurological phenotypes in patients hospitalized with COVID-19, particularly among those with severe disease

Multinational characterization of neurological phenotypes in patients hospitalized with COVID-19

Neurological complications worsen outcomes in COVID-19. To define the prevalence of neurological conditions among hospitalized patients with a positive SARS-CoV-2 reverse transcription polymerase chain reaction test in geographically diverse multinational populations during early pandemic, we used electronic health records (EHR) from 338 participating hospitals across 6 countries and 3 continents (January-September 2020) for a cross-sectional analysis. We assessed the frequency of International Classification of Disease code of neurological conditions by countries, healthcare systems, time before and after admission for COVID-19 and COVID-19 severity. Among 35,177 hospitalized patients with SARS-CoV-2 infection, there was an increase in the proportion with disorders of consciousness (5.8%, 95% confidence interval [CI] 3.7-7.8%, pFDR < 0.001) and unspecified disorders of the brain (8.1%, 5.7-10.5%, pFDR < 0.001) when compared to the pre-admission proportion. During hospitalization, the relative risk of disorders of consciousness (22%, 19-25%), cerebrovascular diseases (24%, 13-35%), nontraumatic intracranial hemorrhage (34%, 20-50%), encephalitis and/or myelitis (37%, 17-60%) and myopathy (72%, 67-77%) were higher for patients with severe COVID-19 when compared to those who never experienced severe COVID-19. Leveraging a multinational network to capture standardized EHR data, we highlighted the increased prevalence of central and peripheral neurological phenotypes in patients hospitalized with COVID-19, particularly among those with severe disease

Differences in testosterone and its precursors by sex of the offspring in meconium

Prenatal metabolism exerts profound effects on development. The first stool of the newborn, meconium, provides a window into the prenatal metabolic environment. The objective of this study was to examine the feasibility of meconium as a novel matrix to quantify prenatal steroid levels. We quantified parameters of analytical interest regarding the use of meconium, including sample stability. We hypothesized that meconium steroid content would differ by sex, prompting analysis of meconium to test effects of prenatal steroid metabolism. Meconium from 193 newborns enrolled in the Early Autism Risk Longitudinal Investigation (EARLI) study, including 107 males, and 86 females, were analyzed by isotope dilution-liquid chromatography-high resolution mass spectrometry (ID-LC-HRMS) while blinded to identity for testosterone (T), androstenedione (AD), and dehydroepiandrosterone (DHEA). Steroid levels were compared by sex, and investigations of potential trends resulting from sample storage or processing was conducted. The unconjugated steroid content of meconium in ng/g (mean, standard deviation) was for males: T (2.67, 8.99), AD (20.01, 28.12), DHEA (13.96, 23.57) and for females: T (0.82, 1.63), AD (22.32, 24.38), DHEA (21.06, 43.49). T was higher in meconium from males (p=0.0333), and DHEA was higher in meconium from females (p=0.0202). 6 female and 3 male T values were below the limit of detection. No extreme variability in hydration or trend in steroid levels by storage time was detected. Sexually dimorphic levels of hormones may reflect gestational differentiation, and future studies should consider meconium analysis

Differences in testosterone and its precursors by sex of the offspring in meconium

Prenatal metabolism exerts profound effects on development. The first stool of the newborn, meconium, provides a window into the prenatal metabolic environment. The objective of this study was to examine the feasibility of meconium as a novel matrix to quantify prenatal steroid levels. We quantified parameters of analytical interest regarding the use of meconium, including sample stability. We hypothesized that meconium steroid content would differ by sex, prompting analysis of meconium to test effects of prenatal steroid metabolism. Meconium from 193 newborns enrolled in the Early Autism Risk Longitudinal Investigation (EARLI) study, including 107 males, and 86 females, were analyzed by isotope dilution-liquid chromatography-high resolution mass spectrometry (ID-LC-HRMS) while blinded to identity for testosterone (T), androstenedione (AD), and dehydroepiandrosterone (DHEA). Steroids levels were compared by sex, and investigations of potential trends resulting from sample storage or processing was conducted. The unconjugated steroid content of meconium in ng/g (mean, standard deviation) was for males: T (2.67, 8.99), AD (20.01, 28.12), DHEA (13.96, 23.57) and for females: T (0.82, 1.63), AD (22.32, 24.38), DHEA (21.06, 43.49). T was higher in meconium from males (p = 0.0333), and DHEA was higher in meconium from females (p = 0.0202). 6 female and 3 male T values were below the limit of detection. No extreme variability in hydration or trend in steroid levels by storage time was detected. Sexually dimorphic levels of hormones may reflect gestational differentiation, and future studies should consider meconium analysis

Acute respiratory distress syndrome after SARS-CoV-2 infection on young adult population: International observational federated study based on electronic health records through the 4CE consortium.

PurposeIn young adults (18 to 49 years old), investigation of the acute respiratory distress syndrome (ARDS) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been limited. We evaluated the risk factors and outcomes of ARDS following infection with SARS-CoV-2 in a young adult population.MethodsA retrospective cohort study was conducted between January 1st, 2020 and February 28th, 2021 using patient-level electronic health records (EHR), across 241 United States hospitals and 43 European hospitals participating in the Consortium for Clinical Characterization of COVID-19 by EHR (4CE). To identify the risk factors associated with ARDS, we compared young patients with and without ARDS through a federated analysis. We further compared the outcomes between young and old patients with ARDS.ResultsAmong the 75,377 hospitalized patients with positive SARS-CoV-2 PCR, 1001 young adults presented with ARDS (7.8% of young hospitalized adults). Their mortality rate at 90 days was 16.2% and they presented with a similar complication rate for infection than older adults with ARDS. Peptic ulcer disease, paralysis, obesity, congestive heart failure, valvular disease, diabetes, chronic pulmonary disease and liver disease were associated with a higher risk of ARDS. We described a high prevalence of obesity (53%), hypertension (38%- although not significantly associated with ARDS), and diabetes (32%).ConclusionTrough an innovative method, a large international cohort study of young adults developing ARDS after SARS-CoV-2 infection has been gather. It demonstrated the poor outcomes of this population and associated risk factor

Proportion and associated risk ratio of complication classes for the young compared to old adult with ARDS.

Proportion and associated risk ratio of complication classes for the young compared to old adult with ARDS.</p

Flow chart.

Distribution of patients per group (y.o. = years old).</p

Number and percentage of patients per age groups, per sex, per Elixhauser comorbidities for young adult patients with ARDS and non severe young adult patients.

Risk ratio associated in uni- and multivariable analysis.</p

Medication class.

(DOCX)</p

Study workflow.

From EHR extraction to ARDS analysis on aggregated data (HS: healthcare system).</p