Outcomes of SARS-CoV-2 and seasonal viruses among 2 million adults hospitalized for severe acute respiratory infection during the COVID-19 pandemic in Brazil.

BACKGROUND: The outbreak of the COVID-19 pandemic has had a profound impact on the circulation of seasonal respiratory viruses. This study aimed to compare the outcomes of SARS-CoV-2 and seasonal viruses in adults hospitalized with severe acute respiratory infection (SARI) during the COVID-19 pandemic. METHODS: This population-based cohort study included patients aged > 18 years hospitalized for SARI in Brazil between February 2020 and February 2023. The primary outcome was in-hospital mortality. A competing risk analysis was used to account for competing events. RESULTS: In total, 2,159,171 patients were included in the study. SARS-CoV-2 was the predominant virus (98.7%). The cumulative incidence of in-hospital mortality was 33.1%, 31.5%, 21.0%, 18.7%, and 18.6%, for patients positive for SARS-CoV-2, adenovirus, RSV, influenza, and other viruses, respectively. SARS-CoV-2 accounted for 99.3% of the deaths. Older age, male sex, comorbidities, hospitalization in the northern region, and oxygen saturation <95% were the common risk factors for death among all viruses. CONCLUSIONS: In this large cohort study, individuals infected with SARS-CoV-2 or adenovirus had the highest risk of mortality. Irrespective of the virus type, older age, male sex, comorbidities, hospitalization in vulnerable regions, and low oxygen saturation were associated with an increased risk of fatality.

Outcomes of SARS-CoV-2 and Seasonal Viruses Among Children Hospitalized in Brazil.

BACKGROUND AND OBJECTIVES: Understanding how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) interacts with other respiratory viruses is crucial for developing effective public health strategies in the postpandemic era. This study aimed to compare the outcomes of SARS-CoV-2 and seasonal viruses in children and adolescents hospitalized with severe acute respiratory infection (SARI). METHODS: This population-based, retrospective cohort study included children and adolescents hospitalized with SARI from February 2020 to February 2023 in Brazil. The main exposure of interest was viral etiology. The primary outcome was in-hospital mortality. Competing risk analysis was used to account for time dependency and competing events. RESULTS: A total of 235 829 patients had available results of the viral tests, with SARS-CoV-2 predominance. According to the competing-risk survival analysis, the estimated probability of a fatal outcome at 30 days of hospitalization according to the viral strain was 6.5%, 3.4%, 2.9%, 2.3%, 2.1%, and 1.8%, for SARS-CoV-2, coinfection, adenovirus, influenza, other viruses, and respiratory syncytial virus, respectively. Individuals with a positive test for SARS-CoV-2 had hazard of death 3 times higher than subjects with a negative test (hazard ratio, 3.3; 95% confidence interval, 3.1-3.5). After adjustment by the competing-risk multivariable analysis, admission in Northeast and North regions, oxygen saturation <95%, and the presence of comorbidities were risk factors for death in all viral strains. CONCLUSIONS: SARS-CoV-2 infection had the highest hazard of in-hospital mortality in this pediatric cohort hospitalized with SARI. Regardless of viral etiology, the presence of underlying medical conditions was a risk factor for death.

Nutrition in Children With Chronic Kidney Disease: How to Thrive?

The nutritional status and management of children with chronic kidney disease (CKD) are complex and require a combined pediatric nephrology team work approach with physicians, nutritionists, nurses, and physical/occupational therapists. Prospective observational studies such as Children with CKD in the US, the 4C study in Europe and the International Pediatric Peritoneal Dialysis Network have advanced the field. However, most recommendations and guidelines from international task forces such as Kidney Diseases Improving Global Outcomes and Pediatric Renal Nutrition Taskforce are opinion-based rather than evidence-based. There is exciting ongoing research to improve nutrition in children with CKD to help them thrive.

Association of Prior COVID-19 Vaccination With SARS-CoV-2 Infection and Death in Children and Young Persons During the Omicron Variant Period in Brazil.

This case-control study evaluates nationwide information surveillance systems in Brazil to estimate vaccine effectiveness against outcomes of COVID-19 in children and young persons.

Perennial grass root system specializes for multiple resource acquisitions with differential elongation and branching patterns.

Roots optimize the acquisition of limited soil resources, but relationships between root forms and functions have often been assumed rather than demonstrated. Furthermore, how root systems co-specialize for multiple resource acquisitions is unclear. Theory suggests that trade-offs exist for the acquisition of different resource types, such as water and certain nutrients. Measurements used to describe the acquisition of different resources should then account for differential root responses within a single system. To demonstrate this, we grew Panicum virgatum in split-root systems that vertically partitioned high water availability from nutrient availability so that root systems must absorb the resources separately to fully meet plant demands. We evaluated root elongation, surface area, and branching, and we characterized traits using an order-based classification scheme. Plants allocated approximately 3/4th of primary root length towards water acquisition, whereas lateral branches were progressively allocated towards nutrients. However, root elongation rates, specific root length, and mass fraction were similar. Our results support the existence of differential root functioning within perennial grasses. Similar responses have been recorded in many plant functional types suggesting a fundamental relationship. Root responses to resource availability can be incorporated into root growth models via maximum root length and branching interval parameters.

Redox Signaling in Chronic Kidney Disease-Associated Cachexia.

Redox signaling alterations contribute to chronic kidney disease (CKD)-associated cachexia. This review aims to summarize studies about redox pathophysiology in CKD-associated cachexia and muscle wasting and to discuss potential therapeutic approaches based on antioxidant and anti-inflammatory molecules to restore redox homeostasis. Enzymatic and non-enzymatic systems of antioxidant molecules have been studied in experimental models of kidney diseases and patients with CKD. Oxidative stress is increased by several factors present in CKD, including uremic toxins, inflammation, and metabolic and hormone alterations, leading to muscle wasting. Rehabilitative nutritional and physical exercises have shown beneficial effects for CKD-associated cachexia. Anti-inflammatory molecules have also been tested in experimental models of CKD. The importance of oxidative stress has been shown by experimental studies in which antioxidant therapies ameliorated CKD and its associated complications in the 5/6 nephrectomy model. Treatment of CKD-associated cachexia is a challenge and further studies are necessary to investigate potential therapies involving antioxidant therapy.

Effectiveness of BNT162b2 and CoronaVac vaccines against omicron in children aged 5 to 11 years.

BACKGROUND: This study aimed to estimate vaccine effectiveness (VE) against omicron variant infection and severe corona virus disease 2019 (COVID-19) in children aged 5-11 years hospitalized with acute respiratory syndrome. METHODS: A test-negative, case-control analysis was conducted from February 2022 to June 2022. We enrolled 6950 eligible children, including 1102 cases and 5848 controls. VE was calculated after immunization with one and two doses of BNT162b2 or CoronaVac. The outcomes were hospitalization with acute respiratory symptoms and detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19. The adjusted odds ratio for the association of prior vaccination and outcomes was used to estimate VE. RESULTS: For fully vaccinated children, the overall estimated VE against hospitalization with SARS-CoV-2 infection was 42% [95% confidence interval (CI) 26 to 54]. VE peaked at 29-42 days (67%, 95% CI 40% to 82%) and then declined to 19% (95% CI, - 20% to 45%) at 57-120 days after the second dose. The BNT162b2 vaccine had a similar VE against hospitalization with SARS-CoV-2 infection (45%, 95% CI, 20 to 61) compared to the CoronaVac vaccine (40%, 95% CI, 17% to 56%). Among cases, 56 (5%) children died; 53 (94.6%) were not fully vaccinated. For cases, the two-dose schedule effectiveness against ICU admission, need for invasive ventilation, severe illness, and death were 10% (95% CI, - 54%-45%), 22% (95% CI - 70%-68%), 12% (95% CI, - 62%-52%), and 16% (95% CI, - 77%-75%), respectively. CONCLUSIONS: For hospitalized children aged 5-11 years during the omicron-predominant period in Brazil, two doses of both vaccines had moderate effectiveness against hospitalization with acute respiratory symptoms and SARS-CoV-2 infection and offered limited protection against endpoints of COVID-19 severity.

Maternal risk factors for congenital anomalies of the kidney and urinary tract: A case-control study.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) are significant causes of pediatric morbidity and mortality. The spectrum of CAKUT can be part of a syndrome, but most of these abnormalities occur as isolated and sporadic forms. The etiology of human CAKUT is unknown in the majority of cases. This case-control study aimed to investigate the association between maternal characteristics and the occurrence of CAKUT and specific CAKUT phenotypes. METHODS: In this case-control study, 29,653 newborns were evaluated consecutively in a tertiary neonatal unit using the Latin American Collaborative Study of Congenital Malformations (ECLAMC) registry. Newborns without congenital anomalies were matched to CAKUT cases by sex, date, and place of birth at a ratio of 3:1. For analysis purposes, the cases were stratified into four subgroups: upper tract abnormalities (UTA), including ureteropelvic junction obstruction, vesicoureteral reflux, primary megaureter and others (n = 239), lower urinary tract obstruction (LUTO) (n = 79), cystic diseases (n = 59) and agenesis/hypodysplasia (n = 28). Multivariable logistic regression analyses were used to calculate crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for associations between the maternal risk factors and the presence of CAKUT. RESULTS: The prevalence of non-syndromic CAKUT in our sample was 13 per 1000 live births. Data records allowed the analysis of 405 cases and 1208 controls. After adjustment by the binary regression logistic, three covariates remained associated as risk factors for the entire spectrum of CAKUT: consanguinity (Odds ratio [OR], 7.1, 95%CI, 2.4-20.4), family history of CAKUT (OR, 6.4, 95%CI, 1.9-21.3), and maternal chronic hypertension (OR, 14.69, 95%CI, 3.2-67.5) (Figure). These risk factors persisted consistently across the various CAKUT phenotypes with minor variations. Consanguinity was the only factor consistently associated with almost all CAKUT phenotypes. Maternal hypertension was associated with all phenotypes except for the agenesis/hypodysplasia group. The prevalence of CAKUT cases was 15 times higher in hypertensive mothers (3%) compared to normotensive mothers (0.2%). CONCLUSION: Our study suggests that an increased risk of CAKUT is associated with consanguinity, a positive family history of CAKUT, and maternal hypertension. However, the prevalence of these risk factors in our cohort was rare and most cases presented as sporadic forms.

The association between pre-existing asthma and reduced risk of death among children and adolescents hospitalized with COVID-19 in Brazil.

OBJECTIVE: There have been conflicting reports on the relationship between asthma and COVID-19 severity. This study aimed to compare the risk of death among children with asthma and healthy peers hospitalized due to COVID-19. METHODS: We carried out an analysis of all pediatric patients 2-19 years of age with asthma and COVID-19 registered in Influenza Epidemiological Surveillance Information System-Gripe, a Brazilian nationwide surveillance database, between February 2020 and March 2022. The primary outcome was time to death, which was evaluated considering discharge as a competitive risk using the cumulative incidence function. RESULTS: Among 30,405 hospitalized children with COVID-19, 21,340 (70.2%) had no comorbidities, 6444 (21.2%) had comorbidities other than asthma, 2165 (7.1%) had asthma, and 465 (1.5%) had asthma with other comorbidities. The estimated probability of a fatal outcome for each group was 4.1%, 14.9%, 2.1%, and 10.7%, respectively. After adjustment, children with asthma had a 60% reduction in the hazard of death than healthy peers (hazard ratio [HR] = 0.39, 95% confidence interval [CI], 0.29-0.53, p < 0.0001). Among children with asthma and no other comorbidities, two covariates were independently associated with in-hospital mortality, age ≥12 years, HR = 4.0, 95% CI, 2.5-6.4), and low oxygen saturation at admission (HR = 2.3, 95% CI, 1.4-3.2). CONCLUSION: Children with asthma and no comorbidities had a lower risk of death compared with healthy peers after controlling for clinical and demographic confounding factors.

Vaccine Effectiveness against SARS-CoV-2 Variants in Adolescents from 15 to 90 Days after Second Dose: A Population-Based Test-Negative Case-Control Study.

OBJECTIVE: The objective of this study was to estimate the vaccine effectiveness (VE) against hospitalization and severe illness in adolescents due to infection with SARS-CoV-2 variants (gamma, delta, and omicron). STUDY DESIGN: A test-negative, case-control analysis was conducted in Brazil from July 2021 to March 2022. We enrolled 8458 eligible individuals (12-19 years of age) hospitalized with an acute respiratory syndrome, including 3075 cases with laboratory-proven COVID-19 and 4753 controls with negative tests for COVID-19. The primary exposure of interest was vaccination status. The primary outcome was SARS-CoV-2 infection during gamma/delta vs omicron-predominant periods. The aOR for the association of prior vaccination and outcomes was used to estimate VE. RESULTS: In the pre-omicron period, VE against COVID-19 hospitalization was 88% (95% CI, 83%-92%) and has dropped to 59% (95% CI, 49%-66%) during the omicron period. For hospitalized cases of COVID-19, considering the entire period of the analysis, 2-dose schedule was moderately effective against intensive care unit admission (46%, [95% CI, 27-60]), need of mechanical ventilation (49%, [95% CI, 32-70]), severe COVID-19 (42%, [95% CI, 17-60]), and death (46%, [95% CI, 8-67]). There was a substantial reduction of about 40% in the VE against all end points, except for death, during the omicron-predominant period. Among cases, 240 (6.6%) adolescents died; of fatal cases, 224 (93.3%) were not fully vaccinated. CONCLUSION: Among adolescents, the VE against all end points was substantially reduced during the omicron-predominant period. Our findings suggest that the 2-dose regimen may be insufficient for SARS-CoV-2 variants and support the need for updated vaccines to provide better protection against severe COVID-19.

Outcomes and risk factors for death among hospitalized children and adolescents with kidney diseases and COVID-19: an analysis of a nationwide database.

BACKGROUND: Patients with kidney diseases (KD) appear to be at particularly high risk for severe COVID-19. This study aimed to characterize the clinical outcomes and risk factors for COVID-19-related death in a large cohort of hospitalized pediatric patients with KD. METHODS: We performed an analysis of all pediatric patients with KD and COVID-19 registered in SIVEP-Gripe, a Brazilian nationwide surveillance database, between February 16, 2020, and May 29, 2021. The primary outcome was time to death, which was evaluated considering discharge as a competitive risk by using cumulative incidence function. RESULTS: Among 21,591 hospitalized patients with COVID-19, 290 cases (1.3%) had KD. Of these, 59 (20.8%) had a fatal outcome compared with 7.5% of the non-KD cohort (P < 0.001). Pediatric patients with KD had an increased hazard of death compared with the non-KD cohort (Hazard ratio [HR] = 2.85, 95% CI 2.21-3.68, P < 0.0001). After adjustment, the factors associated with the death among KD patients were living in Northeast (HR 2.16, 95% CI 1.13-4.31) or North regions (HR 3.50, 95% CI 1.57-7.80), oxygen saturation < 95% at presentation (HR 2.31, 95% CI 1.30-4.10), and presence of two or more associated comorbidities (HR 2.10, 95% CI 1.08-4.04). CONCLUSIONS: Children and adolescents with KD had a higher risk of death compared with the non-KD cohort. The higher risk was associated with low oxygen saturation at admission, living in socioeconomically disadvantaged regions, and presence of other pre-existing comorbidities. A higher resolution version of the Graphical abstract is available as Supplementary information.

Clinical Impact and Risk Factors of Mortality in Hospitalized Children and Adolescents With Hematologic Diseases and COVID-19: An Observational Retrospective Cohort Study.

This study aimed to evaluate the risk factors for COVID-19-related death in a large cohort of hospitalized children with hematological disorders. We performed an analysis of all pediatric patients with COVID-19 registered in a Brazilian nationwide surveillance database between February 2020 and May 2021. The primary outcome was time to death, which was evaluated considering discharge as a competitive risk by using the cumulative incidence function. Among 21,591 hospitalized pediatric patients with COVID-19, 596 cases (2.8%) had hematological diseases. Sixty-one children (27.4%) with malignant hematological diseases had a fatal outcome as compared with 4.2% and 7.4% of nonmalignant hematological and nonhematological cohorts, respectively ( P <0.0001). Children with hematological diseases had a significant increased hazard of death compared with those without these conditions (hazard ratio [HR],=2.40, 95% confidence interval, 1.98 - 2.91). In multivariable analysis, the factors associated with death were the presence of malignant hematological disease (HR, 2.22, 95% CI 1.47 - 3.36), age >10 years (HR 2.19, 95% CI 1.46 - 3.19), male (HR 1.52, 95% CI 1.02 - 2.27), oxygen saturation <95% (HR 2.02, 95% CI 1.38 - 2.96), and abdominal pain at admission (HR 2.75, 95% CI 1.76 - 4.27). Children with malignant hematological diseases had a higher risk of death compared with those without these disorders.

Growth Hormone Improves Adipose Tissue Browning and Muscle Wasting in Mice with Chronic Kidney Disease-Associated Cachexia.

Cachexia associated with chronic kidney disease (CKD) has been linked to GH resistance. In CKD, GH treatment enhances muscular performance. We investigated the impact of GH on cachexia brought on by CKD. CKD was induced by 5/6 nephrectomy in c57BL/6J mice. After receiving GH (10 mg/kg/day) or saline treatment for six weeks, CKD mice were compared to sham-operated controls. GH normalized metabolic rate, increased food intake and weight growth, and improved in vivo muscular function (rotarod and grip strength) in CKD mice. GH decreased uncoupling proteins (UCP)s and increased muscle and adipose tissue ATP content in CKD mice. GH decreased lipolysis of adipose tissue by attenuating expression and protein content of adipose triglyceride lipase and protein content of phosphorylated hormone-sensitive lipase in CKD mice. GH reversed the increased expression of beige adipocyte markers (UCP-1, CD137, Tmem26, Tbx1, Prdm16, Pgc1α, and Cidea) and molecules implicated in adipose tissue browning (Cox2/Pgf2α, Tlr2, Myd88, and Traf6) in CKD mice. Additionally, GH normalized the molecular markers of processes connected to muscle wasting in CKD, such as myogenesis and muscle regeneration. By using RNAseq, we previously determined the top 12 skeletal muscle genes differentially expressed between mice with CKD and control animals. These 12 genes' aberrant expression has been linked to increased muscle thermogenesis, fibrosis, and poor muscle and neuron regeneration. In this study, we demonstrated that GH restored 7 of the top 12 differentially elevated muscle genes in CKD mice. In conclusion, GH might be an effective treatment for muscular atrophy and browning of adipose tissue in CKD-related cachexia.

Global scientific production in the pre-Covid-19 Era: An analysis of 53 countries for 22 years.

Based on an extensive analysis of public databases, we provide an overview of the global scientific output and describe the dynamics of the profound changes in the scientific enterprise during the last decades. The analysis included the scientific production of 53 countries over the 1996-2018 period. During this period, the production of articles per year has tripled. There was a strong correlation between the growth of the global gross domestic product and the increase in the number of articles (R2 = 0.973, P<0.001). Six countries showed a robust increment of their scientific production and are currently among the top 20 in the ranking of world scientific production (China, India, South Korea, Brazil, Turkey, and Iran). The mean annual growth rate was about 12.7% for these six countries. The share of the global scientific production of these countries increased from 7% in 1996 to 27.8% in 2018. Conversely, the participation of the 10 most traditional countries has dropped from 73% to 45% during the same period. In conclusion, we believe that our findings may contribute to further studies aiming to evaluate the impact and changes of the scientific endeavor over the next years in light of the forthcoming new world framework.

Metabolic Advantage of 25(OH)D3 versus 1,25(OH)2D3 Supplementation in Infantile Nephropathic Cystinosis-Associated Adipose Tissue Browning and Muscle Wasting.

Manifestations of infantile nephropathic cystinosis (INC) often include cachexia and deficiency of circulating vitamin D metabolites. We examined the impact of 25(OH)D3 versus 1,25(OH)2D3 repletion in Ctns null mice, a mouse model of INC. Six weeks of intraperitoneal administration of 25(OH)D3 (75 µg/kg/day) or 1,25(OH)2D3 (60 ng/kg/day) resulted in Ctns-/- mice corrected low circulating 25(OH)D3 or 1,25(OH)2D3 concentrations. While 25(OH)D3 administration in Ctns-/- mice normalized several metabolic parameters characteristic of cachexia as well as muscle function in vivo, 1,25(OH)2D3 did not. Administration of 25(OH)D3 in Ctns-/- mice increased muscle fiber size and decreased fat infiltration of skeletal muscle, which was accompanied by a reduction of abnormal muscle signaling pathways. 1,25(OH)2D3 administration was not as effective. In conclusion, 25(OH)D3 supplementation exerts metabolic advantages over 1,25(OH)2D3 supplementation by amelioration of muscle atrophy and fat browning in Ctns-/- mice.

Outcomes and risk factors of death among hospitalized children and adolescents with obesity and COVID-19 in Brazil: An analysis of a nationwide database.

BACKGROUND: Obesity is a well-recognized risk factor for critical illness and death among adult patients with SARS-CoV-2 infection. OBJECTIVE: This study aimed to characterize the clinical outcomes and risk factors of death related to obesity in a cohort of hospitalized paediatric patients with COVID-19. METHODS: We performed an analysis of all paediatric patients with obesity and COVID-19 registered in SIVEP-Gripe, a Brazilian nationwide surveillance database, between February 2020 and May 2021. The primary outcome was time to death, which was evaluated by using cumulative incidence function. RESULTS: Among 21 591 hospitalized paediatric patients with COVID-19, 477 cases (2.2%) had obesity. Of them, 71 (14.9%) had a fatal outcome as compared with 7.5% for patients without obesity (hazard ratio [HR] = 2.0, 95% confidence interval [CI] 1.59-2.53, p < 0.001). After adjustment, the factors associated with death among patients with obesity were female gender (HR = 2.8, 95% CI 1.70-4.61), oxygen saturation < 95% (HR = 2.58, 95% CI 1.38-4.79), presence of one (HR = 1.91, 95% CI 1.11-3.26), and two or more comorbidities (HR = 4.0, 95% CI 2.21-7.56). CONCLUSIONS: Children and adolescents with obesity had higher risk of death compared with those without obesity. The higher risk of death was associated with female gender, low oxygen saturation at admission, and presence of other comorbidities.