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.

Community-acquired pneumonia severity assessment tools in patients hospitalized with COVID-19: a validation and clinical applicability study.

OBJECTIVE: To externally validate community-acquired pneumonia (CAP) tools on patients hospitalized with coronavirus disease 2019 (COVID-19) pneumonia from two distinct countries, and compare their performance with recently developed COVID-19 mortality risk stratification tools. METHODS: We evaluated 11 risk stratification scores in a binational retrospective cohort of patients hospitalized with COVID-19 pneumonia in São Paulo and Barcelona: Pneumonia Severity Index (PSI), CURB, CURB-65, qSOFA, Infectious Disease Society of America and American Thoracic Society Minor Criteria, REA-ICU, SCAP, SMART-COP, CALL, COVID GRAM and 4C. The primary and secondary outcomes were 30-day in-hospital mortality and 7-day intensive care unit (ICU) admission, respectively. We compared their predictive performance using the area under the receiver operating characteristics curve (AUC), sensitivity, specificity, likelihood ratios, calibration plots and decision curve analysis. RESULTS: Of 1363 patients, the mean (SD) age was 61 (16) years. The 30-day in-hospital mortality rate was 24.6% (228/925) in São Paulo and 21.0% (92/438) in Barcelona. For in-hospital mortality, we found higher AUCs for PSI (0.79, 95% CI 0.77-0.82), 4C (0.78, 95% CI 0.75-0.81), COVID GRAM (0.77, 95% CI 0.75-0.80) and CURB-65 (0.74, 95% CI 0.72-0.77). Results were similar for both countries. For the 1%-20% threshold range in decision curve analysis, PSI would avoid a higher number of unnecessary interventions, followed by the 4C score. All scores had poor performance (AUC <0.65) for 7-day ICU admission. CONCLUSIONS: Recent clinical COVID-19 assessment scores had comparable performance to standard pneumonia prognostic tools. Because it is expected that new scores outperform older ones during development, external validation studies are needed before recommending their use.

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.

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/).

Dysfunction of the hypothalamic-pituitary-adrenal axis in critical illness: a narrative review for emergency physicians.

The stress response to acute disease is characterized by activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathoadrenal system, increased serum cortisol levels, increased percentage of its free fraction and increased nuclear translocation of the glucocorticoid-receptor complex, even though many pathways may be inhibited by poorly understood mechanisms. There is no consensus about the cutoff point of serum cortisol levels for defining adrenal insufficiency. Furthermore, recent data point to the participation of tissue resistance to glucocorticoids in acute systemic inflammatory processes. In this review, we evaluate the evidence on HPA axis dysfunction during critical illness, particularly its action on the inflammatory response, during acute severe injury and some pitfalls surrounding the issue. Critical illness-related corticosteroid insufficiency was defined as a dynamic condition characterized by inappropriate cellular activity of corticosteroids for the severity of the disease, manifested by persistently elevated proinflammatory mediators. There is no consensus regarding the diagnostic criteria and treatment indications of this syndrome. Therefore, the benefits of administering corticosteroids to critically ill patients depend on improvements in our knowledge about the possible disruption of its fragile signalling structure in the short and long term.

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.

[Evaluation of venous thromboembolism prophylaxis in a high complexity hospital]. / Avaliação da profilaxia do tromboembolismo venoso em hospital de grande porte.

OBJECTIVE: This study aimed at assessing the adequacy of thromboprophylaxis in a high complexity hospital in Vitória-ES, analysing the possible predictors of inadequate prescriptions and/or procedures. METHODS: A cross-sectional study was carried out through prompt-book analysis. The included patients were hospitalized in 2007 and had their Venous thromboembolism (VTE) risk stratified using the 8th Edition of the American College of Chest Physicians (ACCP) Evidence-Based Clinical Practice Guidelines. The thromboprophylaxis adequacy was determined through a comparison between the adopted prescriptions and/or procedures and the guideline recommendations. EpiInfo 3.4.3 and SPSS 13.0 were the software applications used. RESULTS: In 47% of the patients the thromboprophylaxis was inadequate, being the non-prescription of the indicated medication the major reason (33%). There was no statistically significant difference in inadequate tromboprophylaxis rate between clinical and surgical patients, or ward and Intensive care unit (ICU) ones. An inverse relationship was observed between the inadequate tromboprophylaxis rate and the number of VTE risk factors presented by the patients, as well as their age, and the length of hospital stay (p < 0.05). CONCLUSION: The results show alarming levels of thromboprophylaxis inadequacy, inacceptable in these times of well-established published guidelines. Therefore, a continuing education program should be implanted for all the assistance team.

Avaliação da profilaxia do tromboembolismo venoso em hospital de grande porte / Evaluation of venous thromboembolism prophylaxis in a high complexity hospital

OBJETIVO: Avaliar a adequação da tromboprofilaxia em um hospital de grande porte em Vitória-ES, analisando possíveis preditores de aplicação de conduta inadequada. MÉTODOS: Trata-se de um estudo de corte transversal realizado através de análise de prontuários. Os pacientes analisados estiveram internados no hospital durante o ano de 2007, e tiveram seu risco de tromboembolismo venoso estratificado segundo a 8ª Diretriz para Profilaxia do TEV do American College of Chest Physicians (8º ACCP). A adequação da tromboprofilaxia foi determinada de acordo com a concordância entre a conduta instituída e a conduta preconizada nas diretrizes. Foram utilizados os softwares EpiInfo 3.4.3 e SPSS 13.0. RESULTADOS: Em 47 por cento dos pacientes a tromboprofilaxia foi inadequada, sendo a não prescrição da medicação indicada o principal motivo (33 por cento). Não houve diferença estatisticamente significante quando comparadas as taxas de inadequação da tromboprofilaxia entre pacientes clínicos e cirúrgicos, ou, entre pacientes internados em enfermaria e UTI. O número de fatores de risco para TEV foi inversamente proporcional à taxa de inadequação (p<0,05), assim como a faixa etária do paciente e a duração da internação (p<0,05). CONCLUSÃO: Os resultados obtidos apontam para níveis alarmantes de inadequação da tromboprofilaxia, o que evidencia a necessidade de programas de educação continuada no assunto para toda a equipe assistente.

OBJECTIVE: This study aimed at assessing the adequacy of thromboprophylaxis in a high complexity hospital in Vitória - ES, analysing the possible predictors of inadequate prescriptions and/or procedures. METHODS: A cross-sectional study was carried out through prompt-book analysis. The included patients were hospitalized in 2007 and had their Venous thromboembolism (VTE) risk stratified using the 8th Edition of the American College of Chest Physicians (ACCP) Evidence-Based Clinical Practice Guidelines. The thromboprophylaxis adequacy was determined through a comparison between the adopted prescriptions and/or procedures and the guideline recommendations. EpiInfo 3.4.3 and SPSS 13.0 were the software applications used. RESULTS: In 47 percent of the patients the thromboprophylaxis was inadequate, being the non-prescription of the indicated medication the major reason (33 percent). There was no statistically significant difference in inadequate tromboprophylaxis rate between clinical and surgical patients, or ward and Intensive care unit (ICU) ones. An inverse relationship was observed between the inadequate tromboprophylaxis rate and the number of VTE risk factors presented by the patients, as well as their age, and the length of hospital stay (p < 0,05). CONCLUSION: The results show alarming levels of thromboprophylaxis inadequacy, inacceptable in these times of well-established published guidelines. Therefore, a continuing education program should be implanted for all the assistance team.