First-attempt intubation success and complications in patients with COVID-19 undergoing emergency intubation.

Objectives: To evaluate the first-attempt success rates and complications of endotracheal intubation of coronavirus disease 2019 (COVID-19) patients by emergency physicians. Methods: This prospective observational study was conducted from March 24, 2020 through May 28, 2020 at the emergency department (ED) of an urban, academic trauma center. We enrolled patients consecutively admitted to the ED with suspected or confirmed COVID-19 submitted to endotracheal intubation. No patients were excluded. The primary outcome was first-attempt intubation success, defined as successful endotracheal tube placement with the first device passed (endotracheal tube) during the first laryngoscope insertion confirmed with capnography. Secondary outcomes included the following complications: hypotension, hypoxemia, aspiration, and esophageal intubation. Results: A total of 112 patients with confirmed or suspected COVID-19 were enrolled. Median age was 61 years and 61 patients (54%) were men. The primary outcome, first-attempt intubation success, was achieved in 82% of patients. Among the 20 patients who were not intubated on the first attempt, 75% were intubated on the second attempt and 20% on the third attempt; cricothyrotomy was performed in 1 patient. Forty-eight (42%) patients were hypotensive and required norepinephrine immediately post-intubation. Fifty-eight (52%) experienced peri-intubation hypoxemia, and 2 patients (2%) had cardiac arrest. There were no cases of failed intubation resulting in death up to 24 hours after the procedure. Conclusion: Emergency physicians achieve high success rates when intubating COVID19 patients, although complications are frequent. However, these findings should be considered provisional until their generalizability is assessed in their institutions and setting.

Timing to Intubation COVID-19 Patients: Can We Put It Off until Tomorrow?

BACKGROUND: The decision to intubate COVID-19 patients receiving non-invasive respiratory support is challenging, requiring a fine balance between early intubation and risks of invasive mechanical ventilation versus the adverse effects of delaying intubation. This present study analyzes the association between intubation day and mortality in COVID-19 patients. METHODS: We performed a unicentric retrospective cohort study considering all COVID-19 patients consecutively admitted between March 2020 and August 2020 requiring invasive mechanical ventilation. The primary outcome was all-cause mortality within 28 days after intubation, and a Cox model was used to evaluate the effect of time from onset of symptoms to intubation in mortality. RESULTS: A total of 592 (20%) patients of 3020 admitted with COVID-19 were intubated during study period, and 310 patients who were intubated deceased 28 days after intubation. Each additional day between the onset of symptoms and intubation was significantly associated with higher in-hospital death (adjusted hazard ratio, 1.018; 95% CI, 1.005-1.03). CONCLUSION: Among patients infected with SARS-CoV-2 who were intubated and mechanically ventilated, delaying intubation in the course of symptoms may be associated with higher mortality. TRIAL REGISTRATION: The study protocol was approved by the local Ethics Committee (opinion number 3.990.817; CAAE: 30417520.0.0000.0068).

Distinct Outcomes in COVID-19 Patients with Positive or Negative RT-PCR Test.

Identification of the SARS-CoV-2 virus by RT-PCR from a nasopharyngeal swab sample is a common test for diagnosing COVID-19. However, some patients present clinical, laboratorial, and radiological evidence of COVID-19 infection with negative RT-PCR result(s). Thus, we assessed whether positive results were associated with intubation and mortality. This study was conducted in a Brazilian tertiary hospital from March to August of 2020. All patients had clinical, laboratory, and radiological diagnosis of COVID-19. They were divided into two groups: positive (+) RT-PCR group, with 2292 participants, and negative (-) RT-PCR group, with 706 participants. Patients with negative RT-PCR testing and an alternative most probable diagnosis were excluded from the study. The RT-PCR(+) group presented increased risk of intensive care unit (ICU) admission, mechanical ventilation, length of hospital stay, and 28-day mortality, when compared to the RT-PCR(-) group. A positive SARS-CoV-2 RT-PCR result was independently associated with intubation and 28 day in-hospital mortality. Accordingly, we concluded that patients with a COVID-19 diagnosis based on clinical data, despite a negative RT-PCR test from nasopharyngeal samples, presented more favorable outcomes than patients with positive RT-PCR test(s).

Endothelial injury in COVID-19 and septic patients.

Systemic inflammatory response, as observed in sepsis and severe COVID-19, may lead to endothelial damage. Therefore, we aim to compare the extent of endothelial injury and its relationship to inflammation in both diseases. We included patients diagnosed with sepsis (SEPSIS group, n = 21), mild COVID-19 (MILD group, n = 31), and severe COVID-19 (SEVERE group, n = 24). Clinical and routine laboratory data were obtained, circulating cytokines (INF-γ, TNF-α, and IL-10) and endothelial injury markers (E-Selectin, Tissue Factor (TF) and von Willebrand factor (vWF)) were measured. Compared to the SEPSIS group, patients with severe COVID-19 present similar clinical and laboratory data, except for lower circulating IL-10 and E-Selectin levels. Compared to the MILD group, patients in the SEVERE group showed higher levels of TNF-α, IL-10, and TF. There was no clear relationship between cytokines and endothelial injury markers among the three studied groups; however, in SEVERE COVID-19 patients, there is a positive relationship between INF-γ with TF and a negative relationship between IL-10 and vWF. In conclusion, COVID-19 and septic patients have a similar pattern of cytokines and endothelial dysfunction markers. These findings highlight the importance of endothelium dysfunction in COVID-19 and suggest that endothelium should be better evaluated as a therapeutic target for the disease.

Lower peripheral blood Toll-like receptor 3 expression is associated with an unfavorable outcome in severe COVID-19 patients.

The role of innate immunity in COVID-19 is not completely understood. Therefore, this study explored the impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection on the expression of Pattern Recognition Receptors (PRRs) in peripheral blood cells and their correlated cytokines. Seventy-nine patients with severe COVID-19 on admission, according to World Health Organization (WHO) classification, were divided into two groups: patients who needed mechanical ventilation and/or deceased (SEVERE, n = 50) and patients who used supplementary oxygen but not mechanical ventilation and survived (MILD, n = 29); a control group (CONTROL, n = 17) was also enrolled. In the peripheral blood, gene expression (mRNA) of Toll-like receptors (TLRs) 3, 4, 7, 8, and 9, retinoic-acid inducible gene I (RIGI), NOD-like receptor family pyrin domain containing 3 (NLRP3), interferon alpha (IFN-α), interferon beta (IFN-ß), interferon gamma (IFN-γ), interferon lambda (IFN-λ), pro-interleukin(IL)-1ß (pro-IL-1ß), and IL-18 was determined on admission, between 5-9 days, and between 10-15 days. Circulating cytokines in plasma were also measured. When compared to the COVID-19 MILD group, the COVID-19 SEVERE group had lower expression of TLR3 and overexpression of TLR4.

Double-blind, Randomized, Placebo-controlled Trial With N-acetylcysteine for Treatment of Severe Acute Respiratory Syndrome Caused by Coronavirus Disease 2019 (COVID-19).

BACKGROUND: A local increase in angiotensin 2 after inactivation of angiotensin-converting enzyme 2 by severe acute respiratory syndrome coronavirus 2 (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 patients with coronavirus disease 2019 (COVID-19). METHODS: This was a double-blind, randomized, placebo-controlled, single-center trial conducted at the Emergency Department of Hospital das Clínicas, São Paulo, Brazil, to determine whether NAC in high doses can avoid respiratory failure in patients with COVID-19. We enrolled 135 patients with severe COVID-19 (confirmed or suspected), with an oxyhemoglobin saturation <94% or respiratory rate >24 breaths/minute. Patients were randomized to receive NAC 21 g (~300 mg/kg) for 20 hours or dextrose 5%. The primary endpoint was the need for mechanical ventilation. Secondary endpoints were time of mechanical ventilation, admission to the intensive care unit (ICU), time in ICU, and mortality. RESULTS: Baseline characteristics were similar between the 2 groups, with no significant differences in age, sex, comorbidities, medicines taken, and disease severity. Also, groups were similar in laboratory tests and chest computed tomography scan findings. Sixteen patients (23.9%) in the placebo group received endotracheal intubation and mechanical ventilation, compared with 14 patients (20.6%) in the NAC group (P = .675). No difference was observed in secondary endpoints. CONCLUSIONS: Administration of NAC in high doses did not affect the evolution of severe COVID-19. CLINICAL TRIALS REGISTRATION: Brazilian Registry of Clinical Trials (REBEC): U1111-1250-356 (http://www.ensaiosclinicos.gov.br/rg/RBR-8969zg/).

Lung ultrasound score predicts outcomes in COVID-19 patients admitted to the emergency department.

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.