Assessment of the risk of burnout and its associated factors in healthcare professionals during the COVID-19 pandemic: A prospective cohort study.

Introduction: The COVID-19 pandemic resulted in tremendous physical and psychological pressure on healthcare professionals, especially on those working in intensive care units (ICUs) and Emergency Departments (EDs). The present study intended to characterize the profile of these professionals which is associated with burnout and determine the potential predictors of such condition. Methods: A Prospective cohort study was carried out in a tertiary hospital between March 2020 and March 2021, in Salvador, Brazil. A standardized and validated version of the Oldenburg Burnout inventory (OLBI) was applied to assess risk of burnout together with data forms designed to collect information on sociodemographic characteristics and religious beliefs. ICU and ED healthcare professionals were evaluated during off-hours at two distinct periods of the COVID-19 pandemic, in 2020 and in 2021. Differences in the results obtained from each study participant between the timepoints were compared. A binary logistic regression analysis was performed to identify the predictors of burnout development independent of other confounding factors. Results: Seventy-seven healthcare professionals with a median age of 33 (interquartile range [IQR]: 31-37.5) years and predominantly female (72.7%; n = 56) were enrolled. There were 62 professionals at risk of developing burnout through the OLBI. Those had a median age of 33 (IQR: 31-37) and female predominance (71%, n = 44). Disengagement and burnout were the only features which frequencies significantly changed over time, with increasing detection at the latest timepoint. Alcohol consumption was found to be an important risk factor for burnout development [adjusted odds ratio (aOR): 10.8 (95% CI: 1.8-64.2)]. Importantly, working in the ICU [aOR: 0.04 (95%CI: 0.01-0.32)] and the habit of praying daily [aOR: 0.07 (95%CI: 0.01-0.41)] were characteristics linked to reduced odds of burnout. Discussion: Disengagement substantially increased during the COVID-19 pandemic in healthcare professionals. Alcohol consumption favors the onset of burnout whereas habit of praying daily and working in the ICU are protective against such outcome. Institutional policies aimed at minimizing etilism may positively impact mental health of these professionals.

Diagnostic biomarkers for active tuberculosis: progress and challenges.

Tuberculosis (TB) is a leading cause of morbidity and mortality from a single infectious agent, despite being preventable and curable. Early and accurate diagnosis of active TB is critical to both enhance patient care, improve patient outcomes, and break Mycobacterium tuberculosis (Mtb) transmission cycles. In 2020 an estimated 9.9 million people fell ill from Mtb, but only a little over half (5.8 million) received an active TB diagnosis and treatment. The World Health Organization has proposed target product profiles for biomarker- or biosignature-based diagnostics using point-of-care tests from easily accessible specimens such as urine or blood. Here we review and summarize progress made in the development of pathogen- and host-based biomarkers for active TB diagnosis. We describe several unique patient populations that have posed challenges to development of a universal diagnostic TB biomarker, such as people living with HIV, extrapulmonary TB, and children. We also review additional limitations to widespread validation and utilization of published biomarkers. We conclude with proposed solutions to enhance TB diagnostic biomarker validation and uptake.

Calibration and validation of the Pneumonia Shock Score in critically ill patients with SARS-CoV-2 infection, a multicenter prospective cohort study.

Background: Prognostic tools developed to stratify critically ill patients in Intensive Care Units (ICUs), are critical to predict those with higher risk of mortality in the first hours of admission. This study aims to evaluate the performance of the pShock score in critically ill patients admitted to the ICU with SARS-CoV-2 infection. Methods: Prospective observational analytical cohort study conducted between January 2020 and March 2021 in four general ICUs in Salvador, Brazil. Descriptive statistics were used to characterize the cohort and a logistic regression, followed by cross-validation, were performed to calibrate the score. A ROC curve analysis was used to assess accuracy of the models analyzed. Results: Six hundred five adult ICU patients were included in the study. The median age was 63 (IQR: 49-74) years with a mortality rate of 33.2% (201 patients). The calibrated pShock-CoV score performed well in prediction of ICU mortality (AUC of 0.80 [95% Confidence Interval (CI): 0.77-0.83; p-value < 0.0001]). Conclusions: The pShock-CoV score demonstrated robust discriminatory capacity and may assist in targeting scarce ICU resources during the COVID-19 pandemic to those critically ill patients most likely to benefit.

Platelet-monocyte interaction amplifies thromboinflammation through tissue factor signaling in COVID-19.

Accumulating evidence into the pathogenesis of COVID-19 highlights a hypercoagulability state with high risk of life-threatening thromboembolic complications. However, the mechanisms of hypercoagulability and their link to hyperinflammation remain poorly understood. Here, we investigate functions and mechanisms of platelet activation and platelet-monocyte interactions in inflammatory amplification during SARS-CoV-2 infection. We used a combination of immunophenotyping, single-cell analysis, functional assays, and pharmacological approaches to gain insights on mechanisms. Critically ill patients with COVID-19 exhibited increased platelet-monocyte aggregates formation. We identified a subset of inflammatory monocytes presenting high CD16 and low HLA-DR expression as the subset mainly interacting with platelets during severe COVID-19. Single-cell RNA-sequencing analysis indicated enhanced fibrinogen receptor Mac-1 in monocytes from patients with severe COVID-19. Monocytes from patients with severe COVID-19 displayed increased platelet binding and hyperresponsiveness to P-selectin and fibrinogen with respect to tumor necrosis factor-α and interleukin-1ß secretion. Platelets were able to orchestrate monocyte responses driving tissue factor (TF) expression, inflammatory activation, and inflammatory cytokines secretion in SARS-CoV-2 infection. Platelet-monocyte interactions ex vivo and in SARS-CoV-2 infection model in vitro reciprocally activated monocytes and platelets, inducing the heightened secretion of a wide panel of inflammatory mediators. We identified platelet adhesion as a primary signaling mechanism inducing mediator secretion and TF expression, whereas TF signaling played major roles in amplifying inflammation by inducing proinflammatory cytokines, especially tumor necrosis factor-α and interleukin-1ß. Our data identify platelet-induced TF expression and activity at the crossroad of coagulation and inflammation in severe COVID-19.

Immunomodulatory and Anti-fibrotic Effects Following the Infusion of Umbilical Cord Mesenchymal Stromal Cells in a Critically Ill Patient With COVID-19 Presenting Lung Fibrosis: A Case Report.

Background: The patients with coronavirus disease 2019 (COVID-19) associated with severe acute respiratory distress syndrome (ARDS) may require prolonged mechanical ventilation which often results in lung fibrosis, thus worsening the prognosis and increasing fatality rates. A mesenchymal stromal cell (MSC) therapy may decrease lung inflammation and accelerate recovery in COVID-19. In this context, some studies have reported the effects of MSC therapy for patients not requiring invasive ventilation or during the first hours of tracheal intubation. However, this is the first case report presenting the reduction of not only lung inflammation but also lung fibrosis in a critically ill long-term mechanically ventilated patient with COVID-19. Case Presentation: This is a case report of a 30-year-old male patient with COVID-19 under invasive mechanical ventilation for 14 days in the intensive care unit (ICU), who presented progressive clinical deterioration associated with lung fibrosis. The symptoms onset was 35 days before MSC therapy. The patient was treated with allogenic human umbilical-cord derived MSCs [5 × 107 (2 doses 2 days interval)]. No serious adverse events were observed during and after MSC administration. After MSC therapy, PaO2/FiO2 ratio increased, the need for vasoactive drugs reduced, chest CT scan imaging, which initially showed signs of bilateral and peripheral ground-glass, as well as consolidation and fibrosis, improved, and the systemic mediators associated with inflammation decreased. Modulation of the different cell populations in peripheral blood was also observed, such as a reduction in inflammatory monocytes and an increase in the frequency of patrolling monocytes, CD4+ lymphocytes, and type 2 classical dendritic cells (cDC2). The patient was discharged 13 days after the cell therapy. Conclusions: Mesenchymal stromal cell therapy may be a promising option in critically ill patients with COVID-19 presenting both severe lung inflammation and fibrosis. Further clinical trials could better assess the efficacy of MSC therapy in critically ill patients with COVID-19 with lung fibrosis associated with long-term mechanical ventilation.

Correlation Between SARS-Cov-2 Vaccination, COVID-19 Incidence and Mortality: Tracking the Effect of Vaccination on Population Protection in Real Time.

Coronavirus disease 19 (COVID-19) has struck the world since the ending of 2019. Tools for pandemic control were scarce, limited only to social distance and face mask usage. Today, upto 12 vaccines were approved and the rapid development raises questions about the vaccine efficiency. We accessed the public database provided by each country and the number of death, active cases, and tests in order to evaluate how the vaccine is influencing the COVID-19 pandemic. We observed distinct profiles across the countries and it was related to the vaccination start date and we are proposing a new way to manage the vaccination.

In-depth analysis of laboratory parameters reveals the interplay between sex, age, and systemic inflammation in individuals with COVID-19.

BACKGROUND: The progression and severity of COVID-19 vary significantly in the population. While the hallmarks of SARS-CoV-2 and severe COVID-19 within routine laboratory parameters are emerging, the impact of sex and age on these profiles is still unknown. METHODS: A multidimensional analysis was performed involving millions of records of laboratory parameters and diagnostic tests for 178 887 individuals from Brazil, of whom 33 266 tested positive for SARS-CoV-2. Analyzed data included those relating to complete blood cell count, electrolytes, metabolites, arterial blood gases, enzymes, hormones, cancer biomarkers, and others. FINDINGS: COVID-19 induced similar alterations in laboratory parameters in males and females. CRP and ferritin were increased, especially in older men with COVID-19, whereas abnormal liver function tests were common across several age groups, except for young women. Low peripheral blood basophils and eosinophils were more common in the elderly with COVID-19. Both male and female COVID-19 patients admitted to intensive care units displayed alterations in the coagulation system, and higher values for neutrophils, CRP, and lactate dehydrogenase. CONCLUSIONS: Our study uncovered the laboratory profiles of a large cohort of COVID-19 patients, which formed the basis of discrepancies influenced by aging and biological sex. These profiles directly linked COVID-19 disease presentation to an intricate interplay between sex, age, and immune activation.

Are prognostic tools losing accuracy? Development and performance of a novel age-calibrated severity scoring system for critically ill patients.

OBJECTIVE: This study aimed to assess the performance of a commonly used ICU severity score (SAPS3) and determine whether an alternative scoring system may be more accurate across all age strata. METHODS: Retrospective cohort study in a general ICU in Brazil. A secondary analysis was performed with clinical and epidemiological data, present in the first 24 hours of unit admission. Then, a binary logistic regression, followed by cross-validation, was made to develop a novel prognostic tool. ICU mortality was the primary outcome evaluated. RESULTS: A total of 3042 patients were included over the study period between August 2015 and July 2018 with a median age of 67 ± 18.4 years. SAPS3 performed fairly in prediction of ICU mortality, particularly in the 80 years or older subset. Multivariable regression identified variables independently associated with mortality that were used to develop the Age Calibrated ICU Score (ACIS) tool that performed similarly to SAPS3 across age categories, being slightly superior in the very elderly population (AUC 0.80 vs 0.72). CONCLUSIONS: The ACIS offers a robust and simple tool to predict ICU mortality, particularly in an increasingly elderly critical care population.