Different neurological manifestations of 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 multicenter observational study using the International Severe Acute Respiratory and emerging Infection Consortium cohort across 1507 sites worldwide from January/30th/2020 to May/25th/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; 2,972 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 central nervous system (CNS) infection (0.2%). Each occurred more frequently in ICU than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU vs. non-ICU (7.1% vs. 2.3%, P < .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.
Fibromyalgia (FM) is characterized by chronic non-inflammatory widespread pain (CWP) and changes in sympathetic function. In attempt to elucidate the pathophysiological mechanisms of FM we used a well-established CWP animal model. We aimed to evaluate changes in cardiac autonomic balance and baroreflex function in response to CWP induction in rats. CWP was induced by two injections of acidic saline (pH 4.0, n=8) five days apart into the left gastrocnemius muscle. Control animals were injected twice with normal saline (pH 7.2, n=6). One day after the second injection of acidic saline or normal saline, the animals had pulse interval (PI) and systolic arterial pressure (SAP) variability, and spontaneous baroreflex sensitivity (BRS) evaluated. After induction of CWP, there was an increase of power in the low frequency (LF) band of PI spectrum (12.75 ± 1.04 nu), a decrease in the high frequency (HF) band (87.25 ± 1.04 nu) and an increase of LF/HF ratio (0.16 ± 0.01), when compared to control animals (7.83 ± 1.13 nu LF; 92.16 ± 1.13 nu HF; 0.08 ± 0.01 LF/HF). In addition, there was an increase of power in the LF band of SAP spectrum (7.93 ± 1.39 mmHg2) when compared to control animals (2.97 ± 0.61 mmHg2). BRS was lower in acidic saline injected rats (0.59 ± 0.06 ms/mmHg) when compared to control animals (0.71 ± 0.03 ms/mmHg). Our results showed that induction of CWP in rats shifts cardiac sympathovagal balance towards sympathetic predominance and decreases BRS. These data corroborate findings in humans with FM.
Resistance training is one of the most common kind of exercise used nowadays. Long-term high-intensity resistance training are associated with deleterious effects on vascular adjustments. On the other hand, is unclear whether low-intensity resistance training (LI-RT) is able to induce systemic changes in vascular tone. Thus, we aimed to evaluate the effects of chronic LI-RT on endothelial nitric oxide (NO) bioavailability of mesenteric artery and cardiovascular autonomic modulation in healthy rats. Wistar animals were divided into two groups: exercised (Ex) and sedentary (SED) rats submitted to the resistance (40% of 1RM) or fictitious training for 8 weeks, respectively. After LI-RT, hemodynamic measurements and cardiovascular autonomic modulation by spectral analysis were evaluated. Vascular reactivity, NO production and protein expression of endothelial and neuronal nitric oxide synthase isoforms (eNOS and nNOS, respectively) were evaluated in mesenteric artery. In addition, cardiac superoxide anion production and ventricle morphological changes were also assessed. In vivo measurements revealed a reduction in mean arterial pressure and heart rate after 8 weeks of LI-RT. In vitro studies showed an increased acetylcholine (ACh)-induced vasorelaxation and greater NOS dependence in Ex than SED rats. Hence, decreased phenylephrine-induced vasoconstriction was found in Ex rats. Accordingly, LI-RT increased the NO bioavailability under basal and ACh stimulation conditions, associated with upregulation of eNOS and nNOS protein expression in mesenteric artery. Regarding autonomic control, LI-RT increased spontaneous baroreflex sensitivity, which was associated to reduction in both, cardiac and vascular sympathetic modulation. No changes in cardiac superoxide anion or left ventricle morphometric parameters after LI-RT were observed. In summary, these results suggest that RT promotes beneficial vascular adjustments favoring augmented endothelial NO bioavailability and reduction of sympathetic vascular modulation, without evidence of cardiac overload.
The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use.
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