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.

Machine learning algorithms to predict outcomes in children and adolescents with COVID-19: A systematic review.

BACKGROUND AND OBJECTIVES: We aimed to analyze the study designs, modeling approaches, and performance evaluation metrics in studies using machine learning techniques to develop clinical prediction models for children and adolescents with COVID-19. METHODS: We searched four databases for articles published between 01/01/2020 and 10/25/2023, describing the development of multivariable prediction models using any machine learning technique for predicting several outcomes in children and adolescents who had COVID-19. RESULTS: We included ten articles, six (60 % [95 % confidence interval (CI) 0.31 - 0.83]) were predictive diagnostic models and four (40% [95 % CI 0.170.69]) were prognostic models. All models were developed to predict a binary outcome (n= 10/10, 100 % [95 % CI 0.72-1]). The most frequently predicted outcome was disease detection (n=3/10, 30% [95 % CI 0.11-0.60]). The most commonly used machine learning models in the studies were tree-based (n=12/33, 36.3% [95 % CI 0.17-0.47]) and neural networks (n=9/27, 33.2% [95% CI 0.15-0.44]). CONCLUSION: Our review revealed that attention is required to address problems including small sample sizes, inconsistent reporting practices on data preparation, biases in data sources, lack of reporting metrics such as calibration and discrimination, hyperparameters and other aspects that allow reproducibility by other researchers and might improve the methodology.

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.

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.

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.

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.

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 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.

Risk factors for COVID-19-related mortality in hospitalized children and adolescents with diabetes mellitus: An observational retrospective cohort study.

BACKGROUND: Diabetes has been recognized as a major comorbidity for COVID-19 severity in adults. 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 diabetes. METHODS: We performed an analysis of all pediatric patients with diabetes 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 considering discharge as a competitive risk by using cumulative incidence function. RESULTS: Among 21,591 hospitalized pediatric patients with COVID-19, 379 (1.8%) had diabetes. Overall, children and adolescents with diabetes had a higher prevalence of ICU admission (46.6% vs. 26%), invasive ventilation (16.9% vs. 10.3%), and death (15% vs. 7.6%) (all P < 0.0001). Children with diabetes had twice the hazard of death compared with pediatric patients without diabetes (Hazard ratio [HR] = 2.0, 95% CI, 1.58-2.66). Among children with diabetes, four covariates were independently associated with the primary outcome, living in the poorest regions of the country (Northeast, HR, 2.17, 95% CI 1.18-4.01, and North, (HR 4.0, 95% CI 1.79-8.94), oxygen saturation < 95% at admission (HR 2.97, 95% CI 1.64-5.36), presence of kidney disorders (HR 3.39, 95% CI 1.42-8.09), and presence of obesity (HR 3.77, 95% CI 1.83-7.76). CONCLUSION: Children and adolescents with diabetes had a higher risk of death compared with patients without diabetes. The higher risk of death was associated with clinical and socioeconomic factors.

Comparison of the First and Second Waves of the Coronavirus Disease 2019 Pandemic in Children and Adolescents in a Middle-Income Country: Clinical Impact Associated with Severe Acute Respiratory Syndrome Coronavirus 2 Gamma Lineage.

OBJECTIVE: To evaluate the severity and clinical outcomes of the SARS-CoV-2 gamma variant in children and adolescents hospitalized with COVID-19 in Brazil. STUDY DESIGN: In this observational retrospective cohort study, we performed an analysis of all 21 591 hospitalized patients aged <20 years with confirmed SARS-CoV-2 infection registered in a national database in Brazil. The cohort was divided into 2 groups according to the predominance of SARS-CoV-2 lineages (WAVE1, n = 11 574; WAVE2, n = 10 017). The characteristics of interest were age, sex, geographic region, ethnicity, clinical presentation, and comorbidities. The primary outcome was time to death, which was evaluated by competing-risks analysis, using cumulative incidence functions. A predictive Fine and Gray competing-risks model was developed based on the WAVE1 cohort with temporal validation in the WAVE2 cohort. RESULTS: Compared with children and adolescents admitted during the first wave, those admitted during the second wave had significantly more hypoxemia (52.5% vs 41.1%; P < .0001) and intensive care unit admissions (28.3% vs 24.9%; P < .0001) and needed more noninvasive ventilatory support (37.3% vs 31.6%; P < .0001). In-hospital deaths and death rates were 896 (7.7%) in the first wave and 765 (7.6%) in the second wave (P = .07). The prediction model of death included age, ethnicity, region, respiratory symptoms, and comorbidities. In the validation set (WAVE2), the C statistic was 0.750 (95% CI, 0.741-0.758; P < .0001). CONCLUSIONS: This large national study found a more severe spectrum of risk for pediatric patients with COVID-19 caused by the gamma variant. However, there was no difference regarding the probability of death between the waves.