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

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

Hemodiafiltration Decreases Serum Levels of Inflammatory Mediators in Severe Leptospirosis: A Prospective Study

<div><p>Background</p><p>Leptospirosis is a health problem worldwide. Its most severe form is a classic model of sepsis, provoking acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI), with associated mortality that remains unacceptably high. We previously demonstrated that early initiation of sustained low-efficiency dialysis (SLED) followed by daily SLED significantly decreases mortality. However, the mode of clearance can also affect dialysis patient outcomes. Therefore, the objective of this study was to compare the effects of SLED with traditional (diffusive) clearance, via hemodialysis, and SLED with convective clearance, via hemodiafiltration (SLEDf), in patients with severe leptospirosis.</p><p>Methods</p><p>In this prospective study, conducted in the intensive care unit (ICU) from 2009 through 2012, we compared two groups—SLED (n = 19) and SLEDf (n = 20)—evaluating demographic, clinical, and biochemical parameters, as well as serum levels of interleukins, up to the third day after admission. All patients received dialysis early and daily thereafter.</p><p>Results</p><p>During the study period, 138 patients were admitted to our ICU with a diagnosis of leptospirosis; 39 (36 males/3 females) met the criteria for ARDS and AKI. All patients were on mechanical ventilation and were comparable in terms of respiratory parameters. Mortality did not differ between the SLEDf and SLED groups. However, post-admission decreases in the serum levels of interleukin (IL)-17, IL-7, and monocyte chemoattractant protein-1 were significantly greater in the SLEDf group. Direct bilirubin and the arterial oxygen tension/fraction of inspired oxygen ratio were significantly higher in the SLED group. We identified the following risk factors (sensitivities/specificities) for mortality in severe leptospirosis: age ≥ 55 years (67%/91%); serum urea ≥ 204 mg/dl (100%/70%); creatinine ≥ 5.2 mg/dl (100%/58%); Acute Physiology and Chronic Health Evaluation II score ≥ 39.5 (67%/88%); Sequential Organ Failure Assessment score ≥ 20.5 (67%/85%); and inspiratory pressure ≥ 31 mmHg (84%/85%).</p><p>Conclusions</p><p>The mode of dialysis clearance might not affect outcomes in severe leptospirosis.</p></div

Differences between survivors (n = 33) and nonsurvivors (n = 6).

<p>Differences between survivors (n = 33) and nonsurvivors (n = 6).</p

Serum interleukin levels on the first 3 days in the intensive care unit among patients with severe leptospirosis, by type of renal replacement therapy.

<p>Serum interleukin levels on the first 3 days in the intensive care unit among patients with severe leptospirosis, by type of renal replacement therapy.</p

Allopurinol attenuates acute kidney injury following Bothrops jararaca envenomation.

Snakebites have been recognized as a neglected public health problem in several tropical and subtropical countries. Bothrops snakebites frequently complicate with acute kidney injury (AKI) with relevant morbidity and mortality. To date, the only treatment available for Bothrops envenomation is the intravenous administration of antivenom despite its several limitations. Therefore, the study of novel therapies in Bothrops envenomation is compelling. The aim of this study was to evaluate the protective effect of Allopurinol (Allo) in an experimental model of Bothrops jararaca venom (BJ)-associated AKI. Five groups of Wistar rats were studied: Sham, Allo, BJ, BJ+Allo, BJ+ipAllo. BJ (0.25 mg/kg) was intravenously injected during 40'. Saline at same dose and infusion rate was administered to Sham and Allo groups. Allo and BJ+Allo groups received Allo (300 mg/L) in the drinking water 7 days prior to Saline or BJ infusion respectively. BJ+ipAllo rats received intraperitoneal Allo (25 mg/Kg) 40' after BJ infusion. BJ rats showed markedly reduced glomerular filtration rate (GFR, inulin clearance) associated with intense renal vasoconstriction, hemolysis, hemoglobinuria, reduced glutathione and increased systemic and renal markers of nitro-oxidative stress (Nitrotyrosine). Allo ameliorated GFR, renal blood flow (RBF), renal vascular resistance and arterial lactate levels. In addition, Allo was associated with increased serum glutathione as well as reduced levels of plasma and renal Nitrotyrosine. Our data show that Allo attenuated BJ-associated AKI, reduced oxidative stress, improved renal hemodynamics and organ perfusion. It might represent a novel adjuvant approach for Bothrops envenomation, a new use for an old and widely available drug

Allopurinol (Allo) on other systemic parameters following <i>Bothrops jararaca</i> envenomation.

<p>A) Plasma sodium. B) Plasma potassium. C) Fibrinogen. D) Arterial bicarbonate. E) Plasma lactate dehydrogenase (LDH). F) Arterial lactate. G) Plasma uric acid. H) Plasma creatine phosphokinase (CPK). I) Hemoglobinuria (Dipstick: 0: no hemoglobinuria; 1: +; 2: ++; 3: +++). J) Hematocrit. Data are mean ± SEM; Sham (n = 5): control; Allo (n = 5): Allo pretreatment; BJ (n = 6): <i>Bothrops jararaca</i> venom infusion; BJ+Allo (n = 5): BJ+Allo pretreatment ^ap<0.001, ^bp<0.05 vs. Sham; ^cp<0.001, ^dp<0.05 vs. Allo; ^ep<0.001, ^fp<0.05 vs. BJ+Allo.</p

Experimental protocol.

<p>Five groups were studied: Sham (n = 5), Allopurinol (Allo) (n = 5), <i>Bothrops jararaca</i> (BJ) (n = 6), BJ+Allo (n = 5), BJ+ipAllo (n = 6). BJ (0.25 mg/kg) was injected intravenously during 40’. Saline at same dose and infusion rate was administered to Sham and Allo groups. Allo and BJ+Allo groups received Allo (300 mg/L) in the drinking water 7 days prior to Saline/BJ infusion. BJ+ipAllo rats received intraperitoneal Allo (25 mg/Kg) 40’ after BJ infusion.</p

Allopurinol (Allo) attenuates renal dysfunction and improves redox balance.

<p>A) Inulin clearance studies: gold standard assessment of renal function. B) Serum reduced glutathione (GSH). C) Plasma Nitrotyrosine and D) Renal Nitrotyrosine. Data are mean ± SEM; Sham (n = 5): control; Allo (n = 5): Allo pretreatment; BJ (n = 6): <i>Bothrops jararaca</i> venom infusion; BJ+Allo (n = 5): BJ+Allo pretreatment ^ap<0.001, ^bp<0.05 vs. Sham; ^cp<0.001, ^dp<0.05 vs. Allo; ^ep<0.001, ^fp<0.05 vs. BJ+Allo.</p

Update on the Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Guideline of the Brazilian Society of Cardiology-2019

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