Objective: The objective of this study is to evaluate the impact of social distancing resulting from COVID-19 in hospitalizations for infections of the upper airways (URTI), such as acute laryngitis, tracheitis, and otitis media in children aged 0 to 9 years in Brazil, considering that they share the same forms of transmission. Methods: Data on hospitalizations for acute airway changes and their complications in children <9 years old were obtained from the Database of the Brazilian Department of Public Health Informatics for the period 2015 to 2020. These data were also analyzed by macroregions of Brazil (North, Northeast, Southeast, South, and Midwest). The effect of the social distancing strategy on the increase of acute laryngitis, tracheitis, otitis media, and mastitis, as absolute and relative reductions, was calculated by analyzing the annual calculation of 2015-2019 vs 2020. Results: All the hospitalizations compared in the Unified Health System (SUS) for laryngitis and acute tracheitis and otitis media decreased, considering all states of Brazil. The largest reduction in hospitalization reduction was in the North, with -94% in 2015-2019 vs 2020 in cases of laryngitis and acute tracheitis, and in the Midwest, with - 85% in 2015-2019 vs 2020 in cases of otitis media. Conclusion: Hospitalizations for laryngitis, acute tracheitis, and acute otitis media in children <9 years old decreased between March and July 2020 in Brazil, when social distancing measures were adopted due to the COVID-19 pandemic.

Keywords: COVID-19; Laryngitis; Otitis media; Confinement; Children; Hospitalization.

Mycobacterium tuberculosis is one of the most successful human pathogens. Highly virulent strains, which are more easily transmitted than are less virulent strains, elicit variable immune responses. We evaluated the Th1 responses (IFN-γ production) in healthy volunteers after stimulation with various strains. Our results show that the individuals with negative tuberculin skin test (TST) results were not necessarily naive to all of the strains tested, whereas individuals with positive TST results did not respond to all of the strains tested. Drug-resistant strains induced a lower mean level of IFN-γ production than did drug-sensitive strains. One possible practical application of this finding would be for the prediction of responses to treatment, in which it might be advantageous to have knowledge of the estimated IFN-γ production elicited by a specific isolated strain.

Keywords: Tuberculosis; Polymorphism, restriction fragment length; Mycobacterium tuberculosis; Immunity, cellular; Interferon-gamma.

Objective: To evaluate clinical outcomes and factors associated with mortality, focusing on secondary infections, in critically ill patients with COVID-19 in three Brazilian hospitals during the first pandemic wave. Methods: This was a retrospective observational study involving adult patients with COVID-19 admitted to one of the participating ICUs between March and August of 2020. We analyzed clinical features, comorbidities, source of SARS-CoV-2 infection, laboratory data, microbiology data, complications, and causes of death. We assessed factors associated with in-hospital mortality using logistic regression models. Results: We included 645 patients with a mean age of 61.4 years. Of those, 387 (60.0%) were male, 12.9% (83/643) had undergone solid organ transplant, and almost 10% (59/641) had nosocomial COVID-19 infection. During ICU stay, 359/644 patients (55.7%) required invasive mechanical ventilation, 225 (34.9%) needed renal replacement therapy, 337 (52.2%) received vasopressors, and 216 (33.5%) had hospital-acquired infections (HAIs), mainly caused by multidrug-resistant gram-negative bacteria. HAIs were independently associated with a higher risk of death. The major causes of death were refractory shock and multiple organ dysfunction syndrome but not ARDS, as previously reported in the literature. Conclusions: In this study, most of our cohort required invasive mechanical ventilation and almost one third had HAIs, which were independently associated with a higher risk of death. Other factors related to death were Charlson Comorbidity Index, SOFA score at admission, and clinical complications during ICU stay. Nosocomial COVID-19 infection was not associated with death. The main immediate causes of death were refractory shock and multiple organ dysfunction syndrome.

Keywords: COVID-19/mortality; Sepsis; Multiple organ failure.

Objective: To determine the prevalence and the characteristics of Mycoplasma pneumoniae-related community-acquired pneumonia (CAP) and parapneumonic pleural effusion (PPE) in children and adolescents. Methods: This was a retrospective observational study involving 121 patients with CAP/PPE hospitalized in a tertiary referral hospital between 2000 and 2008, divided into six groups according to the etiologic agent (G1 to G6, respectively): M. pneumoniae with or without co-infection, in 44 patients (group 1); etiologic agents other than M. pneumoniae, in 77 (group 2); M. pneumoniae without co-infection, in 34 (group 3); Streptococcus pneumoniae, in 36 (group 4); Staphylococcus aureus, in 31 (group 5); and M. pneumoniae/S. pneumoniae co-infection, in 9 (group 6). Results: In comparison with group 2, group 1 showed higher frequencies of females, dry cough, and previous use of beta-lactam antibiotics; longer duration of symptoms prior to admission; and lower frequencies of use of mechanical ventilation and chest tube drainage. In comparison with groups 4 and 5, group 3 showed higher frequencies of previous use of beta-lactam antibiotics and dry cough; longer duration of symptoms prior to admission; a lower frequency of use of chest tube drainage; a higher mean age and a lower frequency of nausea/vomiting (versus group 4 only); and a lower frequency of use of mechanical ventilation (versus group 5 only). M. pneumoniae/S. pneumoniae co-infection increased the duration of symptoms prior to admission. Conclusions: In this sample, the prevalence of M. pneumoniae-related CAP/PPE was 12.75%. Although the disease was milder than that caused by other microorganisms, its course was longer. Our data suggest that M. pneumoniae-related CAP/PPE in children and adolescents should be more thoroughly investigated in Brazil.

Keywords: Pleural effusion; Empyema, pleural; Pneumonia; Mycoplasma pneumoniae.

The combination of tuberculosis with other diseases can affect tuberculosis treatment within populations. In the present study, social network analysis of data retrieved from the Mexican National Epidemiological Surveillance System was used in order to explore associations between the number of contacts and multimorbidity. The node degree was calculated for each individual with tuberculosis and included information from 242 contacts without tuberculosis. Multimorbidity was identified in 49.89% of individuals. The node degrees were highest for individuals with tuberculosis + HIV infection (p < 0.04) and lowest for those with tuberculosis + pulmonary edema (p < 0.07). Social network analysis should be used as a standard method for monitoring tuberculosis and tuberculosis-related syndemics.

Keywords: Tuberculosis/epidemiology; HIV; Nutrition, public health.

Objective: To provide an update on trends in asthma mortality in Brazil for two age groups: 0-4 years and 5-34 years. Methods: Data on mortality from asthma, as defined in the International Classification of Diseases, were obtained for the 1980-2014 period from the Mortality Database maintained by the Information Technology Department of the Brazilian Unified Health Care System. To analyze time trends in standardized asthma mortality rates, we conducted an ecological time-series study, using regression models for the 0- to 4-year and 5- to 34-year age groups. Results: There was a linear trend toward a decrease in asthma mortality in both age groups, whereas there was a third-order polynomial fit in the general population. Conclusions: Although asthma mortality showed a consistent, linear decrease in individuals ≤ 34 years of age, the rate of decline was greater in the 0- to 4-year age group. The 5- to 34-year group also showed a linear decline in mortality, and the rate of that decline increased after the year 2004, when treatment with inhaled corticosteroids became more widely available. The linear decrease in asthma mortality found in both age groups contrasts with the nonlinear trend observed in the general population of Brazil. The introduction of inhaled corticosteroid use through public policies to control asthma coincided with a significant decrease in asthma mortality rates in both subsets of individuals over 5 years of age. The causes of this decline in asthma-related mortality in younger age groups continue to constitute a matter of debate.

Keywords: Asthma/epidemiology; Asthma/mortality; Asthma/drug therapy.

Objective: To evaluate the performance of lung ultrasound to determine short-term outcomes of patients with COVID-19 admitted to the intensive care unit. Methods: This is a Prospective, observational study. Between July and November 2020, 59 patients were included and underwent at least two LUS assessments using LUS score (range 0-42) on day of admission, day 5th, and 10th of admission. Results: Age was 66.5±15 years, APACHE II was 8.3±3.9, 12 (20%) patients had malignancy, 46 (78%) patients had a non-invasive ventilation/high-flow nasal cannula and 38 (64%) patients required mechanical ventilation. The median stay in ICU was 12 days (IQR 8.5-20.5 days). ICU or hospital mortality was 54%. On admission, the LUS score was 20.8±6.1; on day 5th and day 10th of admission, scores were 27.6±5.5 and 29.4±5.3, respectively (P=0.007). As clinical condition deteriorated the LUS score increased, with a positive correlation of 0.52, P <0.001. Patients with worse LUS on day 5th versus better score had a mortality of 76% versus 33% (OR 6.29, 95%CI 2.01-19.65, p. 0.003); a similar difference was observed on day 10. LUS score of 5th day of admission had an area under the curve of 0.80, best cut-point of 27, sensitivity and specificity of 0.75 and 0.78 respectively. Conclusion: These findings position LUS as a simple and reproducible method to predict the course of COVID-19 patients.

Keywords: Lund diseases; COVID-19; Ultrasonography.

Objective: Studies in the literature regarding the use of remdesivir to treat COVID-19 patients have shown conflicting results. This study sought to answer questions related to the use of remdesivir for the treatment of patients hospitalized with moderate to severe COVID-19. Methods: This was a systematic review and meta-analysis including phase 3 randomized clinical trials (RCTs) and observational cohort studies selected from various databases, comparing patients hospitalized with moderate to severe COVID-19 receiving remdesivir and controls. Results: A total of 207 studies were retrieved, 9 of which met the eligibility criteria and were included in the study. The meta-analysis using RCTs alone showed no statistically significant differences regarding mortality or use of mechanical ventilation/extracorporeal membrane oxygenation between remdesivir and control groups, and the quality of evidence was moderate and low, respectively. The use of remdesivir increased the recovery rate by 6% (95% CI, 3-9); p = 0.004) and the clinical improvement rate by 7% (95% CI, 1-14); p = 0.02). Additionally, no significant differences in mortality were found between remdesivir and control groups when the meta-analysis used observational cohort studies alone (risk difference = -0.01 (95% CI, -0.02 to 0.01; p = 0.32), the quality of evidence being moderate, and the risk of adverse events was 4% ([95% CI, -0.08 to 0.01]; p = 0.09). Conclusions: The use of remdesivir for the treatment of patients with moderate to severe COVID-19 had no significant impact on clinically important outcomes.

Keywords: Antiviral agents; COVID-19; SARS-CoV-2.

This brief communication demonstrates the correlation of persistent respiratory symptoms with functional, tomographic, and transbronchial pulmonary biopsy findings in patients with COVID-19 who had a long follow-up period. We report a series of six COVID-19 patients with pulmonary involvement who presented with persistent dyspnea within 4-15 months of discharge. We performed transbronchial biopsies, and the histopathological pattern consistently demonstrated peribronchial remodeling with interstitial pulmonary fibrosis. Therefore, lung biopsy may be useful in the approach of patients with long COVID-19, although the type of procedure, its precise indication, and the moment to perform it are yet to be clarified. (Brazilian Registry of Clinical Trials-ReBEC; identifier: RBR-8j9kqy [http://www.ensaiosclinicos.gov.br])

Keywords: COVID-19; COVID-19/pathology; Pulmonary fibrosis; Respiratory function tests; Biopsy.

Objective: To answer questions related to the use of anticoagulants in the treatment of COVID-19 patients. Methods: This was a systematic review and meta-analysis of phase 3 randomized controlled trials comparing the use of anticoagulants in non-hospitalized and hospitalized COVID-19 patients. We searched the following databases: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from their inception to January 22, 2022. The risk of bias was assessed by the Cochrane risk-of-bias tool, and the quality of evidence was assessed by the Grading of Recommendations Assessment, Development and Evaluation system. Results: A total of 401 studies were initially selected. Of those, 9 met the inclusion criteria and were therefore analyzed (a total of 6,004 patients being analyzed). In non-hospitalized COVID-19 patients, no significant difference was found between post-discharge prophylactic anticoagulation and no intervention regarding venous thromboembolism or bleeding at 30 days. In hospitalized COVID-19 patients, full anticoagulation resulted in a slight reduction in thrombotic events at 30 days (risk difference, -0.03; 95% CI, -0.06 to -0.00; p = 0.04; I2 = 78%), the quality of evidence being moderate. However, no significant difference was found between full anticoagulation and no intervention regarding the risk of major bleeding, the quality of evidence being very low. No significant difference was found between intermediate- and standard-dose prophylactic anticoagulation (risk difference, -0.01; 95% CI, -0.07 to 0.06; p = 0.81; I2 = 0%), the quality of evidence being very low. Conclusions: Therapeutic anticoagulation appears to have no effect on mortality in COVID-19 patients, resulting in a slight reduction in venous thromboembolism in hospitalized patients.

Keywords: Anticoagulants; COVID-19; SARS-CoV-2.

Objective: The present study aimed to assess the functional status of children diagnosed with COVID-19 at the time of hospitalization and the associations with clinical features. Methods: This prospective cohort study was carried out with children diagnosed with COVID-19 admitted to a tertiary hospital. The patients' functioning was assessed using the pediatric Functional Status Scale (FSS). Results: A total of 62 children with a median age of 3 years old were included in the study, and 70% had some comorbidity prior to the diagnosis of COVID-19. The median length of stay was nine days, during which period five patients died. The FSS assessment of the sample showed that approximately 55% had some functional alteration. The group of patients with the highest FSS scores presented a lengthier hospital stay (p = 0.016), required more oxygen therapy (p < 0.001), mechanical ventilation (p = 0.001), and intensive care unit admissions (p = 0.019), and had more cardiac (p = 0.007), neurological (p = 0.003), and respiratory (p = 0.013) comorbidities. In the multivariate analysis, there was an association between the dependent variable length of stay and the total FSS score (b = 0.349, p = 0.004) and the presence of comorbidities (b = 0.357, p = 0.004). Conclusions: We observed that more than half of the children hospitalized due to COVID-19 had some level of functional change. Greater alterations in functional status were associated with the presence of previous comorbidities, a greater need for ventilatory support, and longer hospital stays.

Keywords: COVID-19, coronavirus, pediatrics, physical functional performance, functional status.