Comparison of systemic inflammatory profiles in COVID-19 and community-acquired pneumonia patients: a prospective cohort study.

BACKGROUND: Inflammatory responses contribute to tissue damage in COVID-19 and community-acquired pneumonia (CAP). Although predictive values of different inflammatory biomarkers have been reported in both, similarities and differences of inflammatory profiles between these conditions remain uncertain. Therefore, we aimed to determine the similarities and differences of the inflammatory profiles between COVID-19 and CAP, and their association with clinical outcomes. METHODS: We report a prospective observational cohort study; conducted in a reference hospital in Latin America. Patients with confirmed COVID-19 pneumonia and CAP were included. Multiplex (Luminex) cytokine assays were used to measure the plasma concentration of 14 cytokines at hospital admission. After comparing similarities and differences in the inflammatory profile between COVID-19 and CAP patients, an unsupervised classification method (i.e., hierarchical clustering) was used to identify subpopulations within COVID-19 and CAP patients. RESULTS: A total of 160 patients were included, 62.5% were diagnosed with COVID-19 (100/160), and 37.5% with CAP (60/160). Using the hierarchical clustering, COVID-19 and CAP patients were divided based on its inflammatory profile: pauci, moderate, and hyper-inflammatory immune response. COVID-19 hyper-inflammatory subpopulation had the highest mortality. COVID-19 hyper-inflammatory subpopulation, compared to pauci-inflammatory, had higher levels of IL-10 (median [IQR] 61.4 [42.0-109.4] vs 13.0 [5.0-24.9], P: < 0.001), IL-6 (48.1 [22.3-82.6] vs 9.1 [0.1-30.4], P: < 0.001), among others. Hyper-inflammatory vs pauci-inflammatory CAP patients were characterized by elevation of IFN2 (48.8 [29.7-110.5] vs 3.0 [1.7-10.3], P: < 0.001), TNFα (36.3 [24.8-53.4] vs 13.1 [11.3-16.9], P: < 0.001), among others. Hyper-inflammatory subpopulations in COVID-19 and CAP compared to the corresponding pauci-inflammatory subpopulations had higher MCP-1. CONCLUSIONS: Our data highlights three distinct subpopulations in COVID-19 and CAP, with differences in inflammatory marker profiles and risks of adverse clinical outcomes. TRIAL REGISTRATION: This is a prospective study, therefore no health care intervention were applied to participants and trial registration is not applicable.

Impact of macrolide treatment on long-term mortality in patients admitted to the ICU due to CAP: a targeted maximum likelihood estimation and survival analysis.

INTRODUCTION: Patients with community-acquired pneumonia (CAP) admitted to the intensive care unit (ICU) have high mortality rates during the acute infection and up to ten years thereafter. Recommendations from international CAP guidelines include macrolide-based treatment. However, there is no data on the long-term outcomes of this recommendation. Therefore, we aimed to determine the impact of macrolide-based therapy on long-term mortality in this population. METHODS: Registered patients in the MIMIC-IV database 16 years or older and admitted to the ICU due to CAP were included. Multivariate analysis, targeted maximum likelihood estimation (TMLE) to simulate a randomised controlled trial, and survival analyses were conducted to test the effect of macrolide-based treatment on mortality six-month (6 m) and twelve-month (12 m) after hospital admission. A sensitivity analysis was performed excluding patients with Pseudomonas aeruginosa or MRSA pneumonia to control for Healthcare-Associated Pneumonia (HCAP). RESULTS: 3775 patients were included, and 1154 were treated with a macrolide-based treatment. The non-macrolide-based group had worse long-term clinical outcomes, represented by 6 m [31.5 (363/1154) vs 39.5 (1035/2621), p < 0.001] and 12 m mortality [39.0 (450/1154) vs 45.7 (1198/2621), p < 0.001]. The main risk factors associated with long-term mortality were Charlson comorbidity index, SAPS II, septic shock, and respiratory failure. Macrolide-based treatment reduced the risk of dying at 6 m [HR (95% CI) 0.69 (0.60, 0.78), p < 0.001] and 12 m [0.72 (0.64, 0.81), p < 0.001]. After TMLE, the protective effect continued with an additive effect estimate of - 0.069. CONCLUSION: Macrolide-based treatment reduced the hazard risk of long-term mortality by almost one-third. This effect remains after simulating an RCT with TMLE and the sensitivity analysis for the HCAP classification.

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study.

BACKGROUND: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). METHODS: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. RESULTS: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83-7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97-2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14-1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25-1.30]). CONCLUSIONS: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable.

The unique metabolic and lipid profiles of patients with severe COVID-19 compared to severe community-acquired pneumonia: a potential prognostic and therapeutic target.

BACKGROUND: Compare the changes and differences in metabolome and lipidome profiles among severe COVID-19 and CAP patients with ARF to identify biomarkers that could be used for personalized diagnosis, prognosis, and treatment. RESEARCH DESIGN AND METHODS: Plasma samples were taken at hospital admission (baseline) and on the 5th day of hospitalization (follow-up) and examined by RP-LC-QTOF-MS and HILIC-LC-QTOF-MS. RESULTS: 127 patients, 17 with CAP and 110 with COVID-19, were included. The analysis revealed 87 altered metabolites, suggesting changes in the metabolism of arachidonic acid, glycerolipids, glycerophospholipids, linoleic acid, pyruvate, glycolysis, among others. Most of these metabolites are involved in inflammatory, hypoxic, and thrombotic processes. At baseline, the greatest differences were found in phosphatidylcholine (PC) 31:4 (p < 0.001), phosphoserine (PS) 34:3 (p < 0.001), and phosphatidylcholine (PC) 36:5 (p < 0.001), all of which were notably decreased in COVID-19 patients. At follow-up, the most dysregulated metabolites were monomethyl-phosphatidylethanolamine (PE-Nme) 40:5 (p < 0.001) and phosphatidylcholine (PC) 38:4 (p < 0.001). CONCLUSIONS: Metabolic and lipidic alterations suggest inhibition of innate anti-inflammatory and anti-thrombotic mechanisms in COVID-19 patients, which might lead to increased viral proliferation, uncontrolled inflammation, and thrombi formation. Results provide novel targets for predictive biomarkers against CAP and COVID-19. TRIAL REGISTRATION: Not applicable.

Streptococcus pneumoniae as a colonizing agent of the Nasopharynx - Oropharynx in adults: A systematic review and meta-analysis.

BACKGROUND: Streptococcus pneumoniae (Spn) is a commensal pathogen that usually colonizes the upper respiratory tract of children. Likewise, Spn colonization has been considered a critical factor in the development of pneumococcal invasive disease. However, Spn prevalence in adults remains unclear. This study performs a systematic review and meta-analysis to explore the prevalence of Spn Nasopharynx - Oropharynx Colonization (NOC) in adults. METHODS: A Systematic review of scientific databases was utilized to identify eligible studies that follow strict selection criteria. Subsequently, a meta-analysis was conducted to establish NOC prevalence in adults (≥18 years old). The heterogeneity and sensitivity analyses were assessed using the microorganism identification technique, sample type, and age subgroups. RESULTS: Initial selection includes 69 studies, with 37 selected for the meta-analysis, involving 23,724 individuals. The overall prevalence (95 % CI) of Spn NOC among adults was 6 % (5-9). The subgroup analysis revealed that young adults (YA), 18-64 years old, had a prevalence of 10 %, whereas older adults (OA), ≥65 years old, had a prevalence of 2 %. The identification of Spn NOC may vary depending on the method of diagnosis used. High heterogeneity (I2 > 90 %) was observed but diminished to 70 % when the analysis was restricted to oropharyngeal swabs as an identification method. Furthermore, heterogeneity decreased to 58 % when exclusively employing traditional culture as the identification method. CONCLUSIONS: This study found a low prevalence of Spn NOC in adults. Notably, the prevalence of Spn NOC was higher in younger adults than in older adults. It is essential to highlight a significant heterogeneity among studies, which indicates there is no standardized method of Spn NOC identification.

Molecular characterization and descriptive analysis of carbapenemase-producing Gram-negative rod infections in Bogota, Colombia.

In this study, the genetic differences and clinical impact of the carbapenemase-encoding genes among the community and healthcare-acquired infections were assessed. This retrospective, multicenter cohort study was conducted in Colombia and included patients infected with carbapenem-resistant Gram-negative rods between 2017 and 2021. Carbapenem resistance was identified by Vitek, and carbapenemase-encoding genes were identified by whole-genome sequencing (WGS) to classify the alleles and sequence types (STs). Descriptive statistics were used to determine the association of any pathogen or gene with clinical outcomes. A total of 248 patients were included, of which only 0.8% (2/248) had community-acquired infections. Regarding the identified bacteria, the most prevalent pathogens were Pseudomonas aeruginosa and Klebsiella pneumoniae. In the WGS analysis, 228 isolates passed all the quality criteria and were analyzed. The principal carbapenemase-encoding gene was blaKPC, specifically blaKPC-2 [38.6% (88/228)] and blaKPC-3 [36.4% (83/228)]. These were frequently detected in co-concurrence with blaVIM-2 and blaNDM-1 in healthcare-acquired infections. Notably, the only identified allele among community-acquired infections was blaKPC-3 [50.0% (1/2)]. In reference to the STs, 78 were identified, of which Pseudomonas aeruginosa ST111 was mainly related to blaKPC-3. Klebsiella pneumoniae ST512, ST258, ST14, and ST1082 were exclusively associated with blaKPC-3. Finally, no particular carbapenemase-encoding gene was associated with worse clinical outcomes. The most identified genes in carbapenemase-producing Gram-negative rods were blaKPC-2 and blaKPC-3, both related to gene co-occurrence and diverse STs in the healthcare environment. Patients had several systemic complications and poor clinical outcomes that were not associated with a particular gene.IMPORTANCEAntimicrobial resistance is a pandemic and a worldwide public health problem, especially carbapenem resistance in low- and middle-income countries. Limited data regarding the molecular characteristics and clinical outcomes of patients infected with these bacteria are available. Thus, our study described the carbapenemase-encoding genes among community- and healthcare-acquired infections. Notably, the co-occurrence of carbapenemase-encoding genes was frequently identified. We also found 78 distinct sequence types, of which two were novel Pseudomonas aeruginosa, which could represent challenges in treating these infections. Our study shows that in low and middle-income countries, such as Colombia, the burden of carbapenem resistance in Gram-negative rods is a concern for public health, and regardless of the allele, these infections are associated with poor clinical outcomes. Thus, studies assessing local epidemiology, prevention strategies (including trials), and underpinning genetic mechanisms are urgently needed, especially in low and middle-income countries.

Long Covid: a global health issue - a prospective, cohort study set in four continents.

INTRODUCTION: A proportion of people develop Long Covid after acute COVID-19, but with most studies concentrated in high-income countries (HICs), the global burden is largely unknown. Our study aims to characterise long-term COVID-19 sequelae in populations globally and compare the prevalence of reported symptoms in HICs and low-income and middle-income countries (LMICs). METHODS: A prospective, observational study in 17 countries in Africa, Asia, Europe and South America, including adults with confirmed COVID-19 assessed at 2 to <6 and 6 to <12 months post-hospital discharge. A standardised case report form developed by International Severe Acute Respiratory and emerging Infection Consortium's Global COVID-19 Follow-up working group evaluated the frequency of fever, persistent symptoms, breathlessness (MRC dyspnoea scale), fatigue and impact on daily activities. RESULTS: Of 11 860 participants (median age: 52 (IQR: 41-62) years; 52.1% females), 56.5% were from HICs and 43.5% were from LMICs. The proportion identified with Long Covid was significantly higher in HICs vs LMICs at both assessment time points (69.0% vs 45.3%, p<0.001; 69.7% vs 42.4%, p<0.001). Participants in HICs were more likely to report not feeling fully recovered (54.3% vs 18.0%, p<0.001; 56.8% vs 40.1%, p<0.001), fatigue (42.9% vs 27.9%, p<0.001; 41.6% vs 27.9%, p<0.001), new/persistent fever (19.6% vs 2.1%, p<0.001; 20.3% vs 2.0%, p<0.001) and have a higher prevalence of anxiety/depression and impact on usual activities compared with participants in LMICs at 2 to <6 and 6 to <12 months post-COVID-19 hospital discharge, respectively. CONCLUSION: Our data show that Long Covid affects populations globally, manifesting similar symptomatology and impact on functioning in both HIC and LMICs. The prevalence was higher in HICs versus LMICs. Although we identified a lower prevalence, the impact of Long Covid may be greater in LMICs if there is a lack of support systems available in HICs. Further research into the aetiology of Long Covid and the burden in LMICs is critical to implement effective, accessible treatment and support strategies to improve COVID-19 outcomes for all.

The short-term cost-effectiveness of once-weekly semaglutide versus once-weekly dulaglutide for the treatment of type 2 diabetes mellitus in Colombian adults.

Background: Type 2 Diabetes Mellitus (T2DM) is a highly prevalent disease worldwide and in Colombia, representing one of the main causes of death and placing a considerable burden on healthcare systems. 13 classes of drugs are approved for the treatment of T2DM, with Glucagon-like Peptide-1 (GLP-1) receptor agonists being a first-line treatment option for patients with or at high risk of certain cardiovascular diseases and chronic kidney disease. The objective of this study is to conduct a short-term cost-effectiveness analysis of once-weekly semaglutide versus once-weekly dulaglutide in Colombian adults with T2DM, from a third-party payer perspective. Methods: Numbers needed to treat were calculated for different single and composite endpoints of the SUSTAIN 7 trial, annual costs for once weekly semaglutide 1.0 mg and dulaglutide 1.5 mg were extracted from the public SISMED database. With these inputs a cost of control model was developed, to obtain the annual cost of bringing one T2DM patient to relevant clinical outcomes by using semaglutide or dulaglutide. Results: Semaglutide was considered cost-effective compared to dulaglutide across all pre-specified endpoints, even in the different scenarios evaluated in the sensitivity analyses, and in a particularly pronounced manner for weight loss outcomes. Semaglutide at a dose of 1.0 mg once-weekly was cost-effective compared to dulaglutide 1.5 mg across all outcomes in the short-term, making it an appropriate first-line choice in the treatment of T2DM when deciding between these two GLP-1 receptor agonists. Conclusions: This is the first short-term cost-effectiveness study of semaglutide and dulaglutide in T2DM Colombian patients. Our modeled results suggest that once-weekly semaglutide represents a cost-effective option for treating individuals with T2DM in Colombia who are not achieving glycaemia control with metformin, and it would be expected to improve HbA1C, promote greater weight loss and reduce costs from a third-payer perspective compared with treatment with dulaglutide.

Major adverse cardiovascular events (MACE) in patients with severe COVID-19 registered in the ISARIC WHO clinical characterization protocol: A prospective, multinational, observational study.

PURPOSE: To determine its cumulative incidence, identify the risk factors associated with Major Adverse Cardiovascular Events (MACE) development, and its impact clinical outcomes. MATERIALS AND METHODS: This multinational, multicentre, prospective cohort study from the ISARIC database. We used bivariate and multivariate logistic regressions to explore the risk factors related to MACE development and determine its impact on 28-day and 90-day mortality. RESULTS: 49,479 patients were included. Most were male 63.5% (31,441/49,479) and from high-income countries (84.4% [42,774/49,479]); however, >6000 patients were registered in low-and-middle-income countries. MACE cumulative incidence during their hospital stay was 17.8% (8829/49,479). The main risk factors independently associated with the development of MACE were older age, chronic kidney disease or cardiovascular disease, smoking history, and requirement of vasopressors or invasive mechanical ventilation at admission. The overall 28-day and 90-day mortality were higher among patients who developed MACE than those who did not (63.1% [5573/8829] vs. 35.6% [14,487/40,650] p < 0.001; 69.9% [6169/8829] vs. 37.8% [15,372/40,650] p < 0.001, respectively). After adjusting for confounders, MACE remained independently associated with higher 28-day and 90-day mortality (Odds Ratio [95% CI], 1.36 [1.33-1.39];1.47 [1.43-1.50], respectively). CONCLUSIONS: Patients with severe COVID-19 frequently develop MACE, which is independently associated with worse clinical outcomes.

Risk factors for developing ventilator-associated lower respiratory tract infection in patients with severe COVID-19: a multinational, multicentre study, prospective, observational study.

Around one-third of patients diagnosed with COVID-19 develop a severe illness that requires admission to the Intensive Care Unit (ICU). In clinical practice, clinicians have learned that patients admitted to the ICU due to severe COVID-19 frequently develop ventilator-associated lower respiratory tract infections (VA-LRTI). This study aims to describe the clinical characteristics, the factors associated with VA-LRTI, and its impact on clinical outcomes in patients with severe COVID-19. This was a multicentre, observational cohort study conducted in ten countries in Latin America and Europe. We included patients with confirmed rtPCR for SARS-CoV-2 requiring ICU admission and endotracheal intubation. Only patients with a microbiological and clinical diagnosis of VA-LRTI were included. Multivariate Logistic regression analyses and Random Forest were conducted to determine the risk factors for VA-LRTI and its clinical impact in patients with severe COVID-19. In our study cohort of 3287 patients, VA-LRTI was diagnosed in 28.8% [948/3287]. The cumulative incidence of ventilator-associated pneumonia (VAP) was 18.6% [610/3287], followed by ventilator-associated tracheobronchitis (VAT) 10.3% [338/3287]. A total of 1252 bacteria species were isolated. The most frequently isolated pathogens were Pseudomonas aeruginosa (21.2% [266/1252]), followed by Klebsiella pneumoniae (19.1% [239/1252]) and Staphylococcus aureus (15.5% [194/1,252]). The factors independently associated with the development of VA-LRTI were prolonged stay under invasive mechanical ventilation, AKI during ICU stay, and the number of comorbidities. Regarding the clinical impact of VA-LRTI, patients with VAP had an increased risk of hospital mortality (OR [95% CI] of 1.81 [1.40-2.34]), while VAT was not associated with increased hospital mortality (OR [95% CI] of 1.34 [0.98-1.83]). VA-LRTI, often with difficult-to-treat bacteria, is frequent in patients admitted to the ICU due to severe COVID-19 and is associated with worse clinical outcomes, including higher mortality. Identifying risk factors for VA-LRTI might allow the early patient diagnosis to improve clinical outcomes.Trial registration: This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable.

A novel model to predict severe COVID-19 and mortality using an artificial intelligence algorithm to interpret chest radiographs and clinical variables.

Background: Patients with coronavirus disease 2019 (COVID-19) could develop severe disease requiring admission to the intensive care unit (ICU). This article presents a novel method that predicts whether a patient will need admission to the ICU and assesses the risk of in-hospital mortality by training a deep-learning model that combines a set of clinical variables and features in chest radiographs. Methods: This was a prospective diagnostic test study. Patients with confirmed severe acute respiratory syndrome coronavirus 2 infection between March 2020 and January 2021 were included. This study was designed to build predictive models obtained by training convolutional neural networks for chest radiograph images using an artificial intelligence (AI) tool and a random forest analysis to identify critical clinical variables. Then, both architectures were connected and fine-tuned to provide combined models. Results: 2552 patients were included in the clinical cohort. The variables independently associated with ICU admission were age, fraction of inspired oxygen (F iO2 ) on admission, dyspnoea on admission and obesity. Moreover, the variables associated with hospital mortality were age, F iO2 on admission and dyspnoea. When implementing the AI model to interpret the chest radiographs and the clinical variables identified by random forest, we developed a model that accurately predicts ICU admission (area under the curve (AUC) 0.92±0.04) and hospital mortality (AUC 0.81±0.06) in patients with confirmed COVID-19. Conclusions: This automated chest radiograph interpretation algorithm, along with clinical variables, is a reliable alternative to identify patients at risk of developing severe COVID-19 who might require admission to the ICU.

The Respiratory Rate-Oxygenation Index predicts failure of post-extubation high-flow nasal cannula therapy in intensive care unit patients: a retrospective cohort study. / Índice de Oxigenação Respiratória prevê falha de pós-extubação com cânula nasal de alto fluxo em pacientes de unidade de terapia intensiva: estudo de coorte retrospectivo.

OBJECTIVE: To investigate the applicability of the Respiratory Rate-Oxygenation Index to identify the risk of high-flow nasal cannula failure in post-extubation pneumonia patients. METHODS: This was a 2-year retrospective observational study conducted in a reference hospital in Bogotá, Colombia. All patients in whom post-extubation high-flow nasal cannula therapy was used as a bridge to extubation were included in the study. The Respiratory Rate-Oxygenation Index was calculated to assess the risk of post-extubation high-flow nasal cannula failure. RESULTS: A total of 162 patients were included in the study. Of these, 23.5% developed high-flow nasal cannula failure. The Respiratory Rate-Oxygenation Index was significantly lower in patients who had high-flow nasal cannula failure [median (IQR): 10.0 (7.7 - 14.4) versus 12.6 (10.1 - 15.6); p = 0.006]. Respiratory Rate-Oxygenation Index > 4.88 showed a crude OR of 0.23 (95%CI 0.17 - 0.30) and an adjusted OR of 0.89 (95%CI 0.81 - 0.98) stratified by severity and comorbidity. After logistic regression analysis, the Respiratory Rate-Oxygenation Index had an adjusted OR of 0.90 (95%CI 0.82 - 0.98; p = 0.026). The area under the Receiver Operating Characteristic curve for extubation failure was 0.64 (95%CI 0.53 - 0.75; p = 0.06). The Respiratory Rate-Oxygenation Index did not show differences between patients who survived and those who died during the intensive care unit stay. CONCLUSION: The Respiratory Rate-Oxygenation Index is an accessible tool to identify patients at risk of failing high-flow nasal cannula post-extubation treatment. Prospective studies are needed to broaden the utility in this scenario.

OBJETIVO: Investigar a aplicabilidade do Índice de Oxigenação Respiratória para identificar o risco de falha de cânula nasal de alto fluxo em pacientes com pneumonia. MÉTODOS: Este estudo retrospectivo observacional de 2 anos foi realizado em um hospital de referência em Bogotá, na Colômbia. Incluíram-se no estudo todos os pacientes em que foi utilizada cânula nasal de alto fluxo pós-extubação como terapia-ponte para a extubação. O Índice de Oxigenação Respiratória foi calculado para avaliar o risco de falha pós-extubação de cânula nasal de alto fluxo. RESULTADOS: Incluíram-se no estudo 162 pacientes. Destes, 23,5% apresentaram falha de cânula nasal de alto fluxo. O Índice de Oxigenação Respiratória foi significativamente menor em pacientes que tiveram falha de cânula nasal de alto fluxo. A mediana (IQ 25 - 75%) foi de 10,0 (7,7 - 14,4) versus 12,6 (10,1 - 15,6), com p = 0,006. O Índice de Oxigenação Respiratória > 4,88 apresentou razão de chances bruta de 0,23 (IC95% 0,17 - 0,30) e RC ajustada de 0,89 (IC95% 0,81 - 0,98) estratificada por gravidade e comorbidade. Após a análise de regressão logística, o Índice de Oxigenação Respiratória apresentou razão de chances ajustada de 0,90 (IC95% 0,82 - 0,98; p = 0,026). A área sob a curva Receiver Operating Characteristic para falha de extubação foi de 0,64 (IC95% 0,53 - 0,75; p = 0,06). O Índice de Oxigenação Respiratória não apresentou diferenças entre pacientes que sobreviveram e que morreram durante internação na unidade de terapia intensiva. CONCLUSÃO: O Índice de Oxigenação Respiratória é uma ferramenta acessível para identificar pacientes em risco de falha no tratamento pós-extubação com cânulas nasais de alto fluxo. Estudos prospectivos são necessários para ampliar a utilidade nesse cenário.

Prevalence, incidence, and severity associated with viral respiratory tract infections in Colombian adults before the COVID-19 pandemic.

BACKGROUND: Acute respiratory illness (ARI) remains the leading cause of global morbidity. Its primary etiology is viral; nevertheless, viral pathogen identification is limited. Clinical information about Latin America's viral etiology, outcomes, and severity is unknown. This study aims to identify the clinical burden of respiratory viral infections, severity, and adult outcomes. METHODS: This multicentric, population-based study was conducted through the Health Institute of Bogotá, Colombia, including adult patients diagnosed with ARI between 2013 and 2019. Data collection followed ARI public health surveillance program. Incidence, etiological pathogens, and mortality were calculated. RESULTS: A total of 2304 patients were included in the study. ARI was most frequently reported in 2018 (23.3% [538/2304]). Incidence varies between years, maintaining a range between 3.5 and 8.4. The most frequent clinical diagnosis was pneumonia in 59.1%. Etiological viral detection was obtained in 21.5% of patients [495/2304], principally by Influenza A. Mortality was 21.8%, and ICU admission was 7.3%. The type of event did not predict the causative pathogen, disease severity, or mortality. CONCLUSIONS: ARI is a leading cause of morbidity and mortality in Colombia. ARI incidence varies per year and is caused mainly by Influenza A. The classification used in the surveillance program does not correlate with viral etiology, disease severity, and mortality.

ISARIC-COVID-19 dataset: A Prospective, Standardized, Global Dataset of Patients Hospitalized with COVID-19.

The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) COVID-19 dataset is one of the largest international databases of prospectively collected clinical data on people hospitalized with COVID-19. This dataset was compiled during the COVID-19 pandemic by a network of hospitals that collect data using the ISARIC-World Health Organization Clinical Characterization Protocol and data tools. The database includes data from more than 705,000 patients, collected in more than 60 countries and 1,500 centres worldwide. Patient data are available from acute hospital admissions with COVID-19 and outpatient follow-ups. The data include signs and symptoms, pre-existing comorbidities, vital signs, chronic and acute treatments, complications, dates of hospitalization and discharge, mortality, viral strains, vaccination status, and other data. Here, we present the dataset characteristics, explain its architecture and how to gain access, and provide tools to facilitate its use.

Dexamethasone as risk-factor for ICU-acquired respiratory tract infections in severe COVID-19.

PURPOSE: Dexamethasone is the only drug that has consistently reduced mortality in patients with COVID-19, especially in patients needing oxygen or invasive mechanical ventilation. However, there is a growing concern about the relation of dexamethasone with the unprecedented rates of ICU-acquired respiratory tract infections (ICU-RTI) observed in patients with severe COVID-19. METHODS: This was a multicenter, prospective cohort study; conducted in ten countries in Latin America and Europe. We included patients older than 18 with confirmed SARS-CoV-2 requiring ICU admission. A multivariate logistic regression and propensity score matching (PSM) analysis was conducted to determine the relation between dexamethasone treatment and ICU-RTI. RESULTS: A total of 3777 patients were included. 2065 (54.7%) were treated with dexamethasone within the first 24 h of admission. After performing the PSM, patients treated with dexamethasone showed significantly higher proportions of VAP (282/1652 [17.1%] Vs. 218/1652 [13.2%], p = 0.014). Also, dexamethasone treatment was identified as an adjusted risk factor of ICU-RTI in the multivariate logistic regression model (OR 1.64; 95%CI: 1.37-1.97; p < 0.001). CONCLUSION: Patients treated with dexamethasone for severe COVID-19 had a higher risk of developing ICU-acquired respiratory tract infections after adjusting for days of invasive mechanical ventilation and ICU length of stay, suggesting a cautious use of this treatment.

Negative predictive value of procalcitonin to rule out bacterial respiratory co-infection in critical covid-19 patients.

BACKGROUND: Procalcitonin (PCT) and C-Reactive Protein (CRP) are useful biomarkers to differentiate bacterial from viral or fungal infections, although the association between them and co-infection or mortality in COVID-19 remains unclear. METHODS: The study represents a retrospective cohort study of patients admitted for COVID-19 pneumonia to 84 ICUs from ten countries between (March 2020-January 2021). Primary outcome was to determine whether PCT or CRP at admission could predict community-acquired bacterial respiratory co-infection (BC) and its added clinical value by determining the best discriminating cut-off values. Secondary outcome was to investigate its association with mortality. To evaluate the main outcome, a binary logistic regression was performed. The area under the curve evaluated diagnostic performance for BC prediction. RESULTS: 4635 patients were included, 7.6% fulfilled BC diagnosis. PCT (0.25[IQR 0.1-0.7] versus 0.20[IQR 0.1-0.5]ng/mL, p<0.001) and CRP (14.8[IQR 8.2-23.8] versus 13.3 [7-21.7]mg/dL, p=0.01) were higher in BC group. Neither PCT nor CRP were independently associated with BC and both had a poor ability to predict BC (AUC for PCT 0.56, for CRP 0.54). Baseline values of PCT<0.3ng/mL, could be helpful to rule out BC (negative predictive value 91.1%) and PCT≥0.50ng/mL was associated with ICU mortality (OR 1.5,p<0.001). CONCLUSIONS: These biomarkers at ICU admission led to a poor ability to predict BC among patients with COVID-19 pneumonia. Baseline values of PCT<0.3ng/mL may be useful to rule out BC, providing clinicians a valuable tool to guide antibiotic stewardship and allowing the unjustified overuse of antibiotics observed during the pandemic, additionally PCT≥0.50ng/mL might predict worsening outcomes.

Clinical characteristics, systemic complications, and in-hospital outcomes for patients with COVID-19 in Latin America. LIVEN-Covid-19 study: A prospective, multicenter, multinational, cohort study.

PURPOSE: The COVID-19 pandemic has spread worldwide, and almost 396 million people have been infected around the globe. Latin American countries have been deeply affected, and there is a lack of data in this regard. This study aims to identify the clinical characteristics, in-hospital outcomes, and factors associated with ICU admission due to COVID-19. Furthermore, to describe the functional status of patients at hospital discharge after the acute episode of COVID-19. MATERIAL AND METHODS: This was a prospective, multicenter, multinational observational cohort study of subjects admitted to 22 hospitals within Latin America. Data were collected prospectively. Descriptive statistics were used to characterize patients, and multivariate regression was carried out to identify factors associated with severe COVID-19. RESULTS: A total of 3008 patients were included in the study. A total of 64.3% of patients had severe COVID-19 and were admitted to the ICU. Patients admitted to the ICU had a higher mean (SD) 4C score (10 [3] vs. 7 [3)], p<0.001). The risk factors independently associated with progression to ICU admission were age, shortness of breath, and obesity. In-hospital mortality was 24.1%, whereas the ICU mortality rate was 35.1%. Most patients had equal self-care ability at discharge 43.8%; however, ICU patients had worse self-care ability at hospital discharge (25.7% [497/1934] vs. 3.7% [40/1074], p<0.001). CONCLUSIONS: This study confirms that patients with SARS CoV-2 in the Latin American population had a lower mortality rate than previously reported. Systemic complications are frequent in patients admitted to the ICU due to COVID-19, as previously described in high-income countries.

Administration and Therapeutic Drug Monitoring of ß-lactams and Vancomycin in Critical Care Units in Colombia: The ANTIBIOCOL Study.

Therapeutic drug monitoring (TDM) and continuous infusion strategies are effective interventions in clinical practice, but these practices are still largely unknown in Colombia, especially in the critical care setting. This study aims to describe the practices involved in the administration and TDM of ß-lactams and vancomycin reported by specialists in critical care in Colombia and to explore the factors that are related to the use of extended infusion. An online nationwide survey was applied to 153 specialists, who were selected randomly. A descriptive, bivariate analysis and a logistic regression model were undertaken. In total, 88.9% of the specialists reported TDM availability and 21.57% reported access to results within 6 h. TDM was available mainly for vancomycin. We found that 85.62% of the intensivists had some type of institutional protocol; however, only 39.22% had a complete and socialized protocol. The odds of preferring extended infusions among those who did not have institutional protocols were 80% lower than those with complete protocols, OR 0.2 (95% CI: 0.06-0.61). The most important perceived barriers to performing continuous infusions and TDM were the lack of training and technologies. This pioneering study in Colombia could impact the quality of care and outcomes of critically ill patients in relation to the threat of antimicrobial resistance.

Índice de Oxigenação Respiratória prevê falha de pós-extubação com cânula nasal de alto fluxo em pacientes de unidade de terapia intensiva: estudo de coorte retrospectivo / The Respiratory Rate-Oxygenation Index predicts failure of post-extubation high-flow nasal cannula therapy in intensive care unit patients: a retrospective cohort study

RESUMO Objetivo: Investigar a aplicabilidade do Índice de Oxigenação Respiratória para identificar o risco de falha de cânula nasal de alto fluxo em pacientes com pneumonia. Métodos: Este estudo retrospectivo observacional de 2 anos foi realizado em um hospital de referência em Bogotá, na Colômbia. Incluíram-se no estudo todos os pacientes em que foi utilizada cânula nasal de alto fluxo pós-extubação como terapia-ponte para a extubação. O Índice de Oxigenação Respiratória foi calculado para avaliar o risco de falha pós-extubação de cânula nasal de alto fluxo. Resultados: Incluíram-se no estudo 162 pacientes. Destes, 23,5% apresentaram falha de cânula nasal de alto fluxo. O Índice de Oxigenação Respiratória foi significativamente menor em pacientes que tiveram falha de cânula nasal de alto fluxo. A mediana (IQ 25 - 75%) foi de 10,0 (7,7 - 14,4) versus 12,6 (10,1 - 15,6), com p = 0,006. O Índice de Oxigenação Respiratória > 4,88 apresentou razão de chances bruta de 0,23 (IC95% 0,17 - 0,30) e RC ajustada de 0,89 (IC95% 0,81 - 0,98) estratificada por gravidade e comorbidade. Após a análise de regressão logística, o Índice de Oxigenação Respiratória apresentou razão de chances ajustada de 0,90 (IC95% 0,82 - 0,98; p = 0,026). A área sob a curva Receiver Operating Characteristic para falha de extubação foi de 0,64 (IC95% 0,53 - 0,75; p = 0,06). O Índice de Oxigenação Respiratória não apresentou diferenças entre pacientes que sobreviveram e que morreram durante internação na unidade de terapia intensiva. Conclusão: O Índice de Oxigenação Respiratória é uma ferramenta acessível para identificar pacientes em risco de falha no tratamento pós-extubação com cânulas nasais de alto fluxo. Estudos prospectivos são necessários para ampliar a utilidade nesse cenário.

ABSTRACT Objective: To investigate the applicability of the Respiratory Rate-Oxygenation Index to identify the risk of high-flow nasal cannula failure in post-extubation pneumonia patients. Methods: This was a 2-year retrospective observational study conducted in a reference hospital in Bogotá, Colombia. All patients in whom post-extubation high-flow nasal cannula therapy was used as a bridge to extubation were included in the study. The Respiratory Rate-Oxygenation Index was calculated to assess the risk of post-extubation high-flow nasal cannula failure. Results: A total of 162 patients were included in the study. Of these, 23.5% developed high-flow nasal cannula failure. The Respiratory Rate-Oxygenation Index was significantly lower in patients who had high-flow nasal cannula failure [median (IQR): 10.0 (7.7 - 14.4) versus 12.6 (10.1 - 15.6); p = 0.006]. Respiratory Rate-Oxygenation Index > 4.88 showed a crude OR of 0.23 (95%CI 0.17 - 0.30) and an adjusted OR of 0.89 (95%CI 0.81 - 0.98) stratified by severity and comorbidity. After logistic regression analysis, the Respiratory Rate-Oxygenation Index had an adjusted OR of 0.90 (95%CI 0.82 - 0.98; p = 0.026). The area under the Receiver Operating Characteristic curve for extubation failure was 0.64 (95%CI 0.53 - 0.75; p = 0.06). The Respiratory Rate-Oxygenation Index did not show differences between patients who survived and those who died during the intensive care unit stay. Conclusion: The Respiratory Rate-Oxygenation Index is an accessible tool to identify patients at risk of failing high-flow nasal cannula post-extubation treatment. Prospective studies are needed to broaden the utility in this scenario.