Background A local increase in angiotensin 2 after inactivation of angiotensin-converting enzyme 2 by SARS-CoV-2 may induce a redox imbalance in alveolar epithelium cells, causing apoptosis, increased inflammation and, consequently, impaired gas exchange. We hypothesized that N-acetylcysteine (NAC) administration could restore this redox homeostasis and suppress unfavorable evolution in Covid-19 patients. Objective To determine whether NAC in high doses can avoid respiratory failure in patients with Covid-19. Methods It was a double-blind, randomized, placebo-controlled, unicentric trial, conducted at the Emergency Department of Hospital das Clínicas, São Paulo, Brazil. We enrolled 135 patients with severe Covid-19 (confirmed or suspected), with an oxyhemoglobin saturation of less than 94% or respiratory rate higher than 24 breaths/min. Patients were randomized to receive NAC 21 g (approximately 300 mg/kg) for 20 hours, or dextrose 5%. Primary endpoint was the need for mechanical ventilation. Secondary endpoints were time of mechanical ventilation, admission to ICU, time in ICU, and mortality. Results Baseline characteristics were very similar in the two groups, with no significant difference in age, sex, comorbidities, medicines taken, and disease severity. Also, groups were similar in laboratory tests and chest CT scan findings. Sixteen patients (23.9%) in the Placebo group were submitted to endotracheal intubation and mechanical ventilation, compared to 14 patients (20.6%) in the NAC group (p=0.675). No difference was observed in secondary endpoints. Conclusion Administration of NAC in high doses did not affect the evolution of severe Covid-19.

Background During the COVID-19 pandemic, creating tools to assess disease severity is one of the most important aspects of reducing the burden on emergency departments. Lung ultrasound has a high accuracy for the diagnosis of pulmonary diseases; however, there are few prospective studies demonstrating that lung ultrasound can predict outcomes in COVID-19 patients. We hypothesized that lung ultrasound score (LUS) at hospital admission could predict outcomes of COVID-19 patients. This is a prospective cohort study conducted from 14 March through 6 May 2020 in the emergency department (ED) of an urban, academic, level I trauma center. Patients aged 18 years and older and admitted to the ED with confirmed COVID-19 were considered eligible. Emergency physicians performed lung ultrasounds and calculated LUS, which was tested for correlation with outcomes. This protocol was approved by the local Ethics Committee number 3.990.817 (CAAE: 30417520.0.0000.0068). Results The primary endpoint was death from any cause. The secondary endpoints were ICU admission and endotracheal intubation for respiratory failure. Among 180 patients with confirmed COVID-19 who were enrolled (mean age, 60 years; 105 male), the average LUS was 18.7 ± 6.8. LUS correlated with findings from chest CT and could predict the estimated extent of parenchymal involvement (mean LUS with < 50% involvement on chest CT, 15 ± 6.7 vs. 21 ± 6.0 with > 50% involvement, p < 0.001), death (AUC 0.72, OR 1.13, 95% CI 1.07 to 1.21; p < 0.001), endotracheal intubation (AUC 0.76, OR 1.17, 95% CI 1.09 to 1.26; p < 0.001), and ICU admission (AUC: 0.71, OR 1.14, 95% CI 1.07 to 1.21; p < 0.001). Conclusions In COVID-19 patients admitted in ED, LUS was a good predictor of death, ICU admission, and endotracheal intubation.

Obesity is a risk factor for the development of asthma. Obese mice exhibit innate airway hyperresponsiveness (AHR), a characteristic feature of asthma, and IL-17A is required for development of AHR in obese mice. The purpose of this study was to examine the temporal association between the onset of AHR and changes in IL-17A during the development of obesity by high-fat feeding in mice. At weaning, C57BL/6J mice were placed either on mouse chow or on a high-fat diet (HFD) and examined 9, 12, 15, 18, or 24 weeks later. Airway responsiveness to aerosolized methacholine (assessed via the forced oscillation technique) was greater in mice fed HFD versus chow for 24 weeks but not at earlier time points. Bronchoalveolar lavage and serum IL-17A were not affected by either the type or duration of diet, but increased pulmonary IL17a mRNA abundance was observed in HFD versus chow fed mice after both 18 and 24 weeks. Flow cytometry also confirmed an increase in IL-17A+ γδ T cells and IL-17A+ CD4+ T (Th17) cells in lungs of HFD versus chow fed mice. Pulmonary expression of Cfd (complement factor D, adipsin), a gene whose expression can be reduced by IL-17A, decreased after both 18 and 24 weeks in HFD versus chow fed mice. Furthermore, pulmonary Cfd mRNA abundance correlated with elevations in pulmonary Il17a mRNA expression and with AHR. Serum levels of TNFα, MIP-1α, and MIP-1β, and classical markers of systemic inflammation of obesity were significantly greater in HFD than chow fed mice after 24 weeks, but not earlier. In conclusion, our data indicate that pulmonary rather than systemic IL-17A is important for obesity-related AHR and suggest that changes in pulmonary Cfd expression contribute to these effects of IL-17A. Further, the observation that increases in Il17a preceded the development of AHR by several weeks suggests that IL-17A interacts with other factors to promote AHR. The observation that the onset of the systemic inflammation of obesity coincided temporally with the development of AHR suggest that systemic inflammation may be one of these factors.

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Background The first cases of coronavirus disease (COVID-19) in Brazil were diagnosed in February 2020. Our Emergency Department (ED) was designated as a COVID-19 exclusive service. We report our first 500 confirmed COVID-19 pneumonia patients. Methods From 14 March to 16 May 2020, we enrolled all patients admitted to our ED that had a diagnosis of COVID-19 pneumonia. Infection was confirmed via nasopharyngeal swabs or tracheal aspirate PCR. The outcomes included hospital discharge, invasive mechanical ventilation, and in-hospital death, among others. Results From 2219 patients received in the ED, we included 506 with confirmed COVID-19 pneumonia. We found that 333 patients were discharged home (65.9%), 153 died (30.2%), and 20 (3.9%) remained in the hospital. A total of 300 patients (59.3%) required ICU admission, and 227 (44.9%) needed invasive ventilation. The multivariate analysis found age, number of comorbidities, extension of ground glass opacities on chest CT and troponin with a direct relationship with all-cause mortality, whereas dysgeusia, use of angiotensin converting enzyme inhibitor or angiotensin-ii receptor blocker and number of lymphocytes with an inverse relationship with all-cause mortality Conclusions This was a sample of severe patients with COVID-19, with 59.2% admitted to the ICU and 41.5% requiring mechanical ventilator support. We were able to ascertain the outcome in majority (96%) of patients. While the overall mortality was 30.2%, mortality for intubated patients was 55.9%. Multivariate analysis agreed with data found in other studies although the use of angiotensin converting enzyme inhibitor or angiotensin-ii receptor blocker as a protective factor could be promising but would need further studies. Trial registration The study was registered in the Brazilian registry of clinical trials: RBR-5d4dj5.