The mechanisms used by SARS-CoV-2 to induce major adverse cardiac events (MACE) are unknown. Thus, we aimed to determine if SARS-CoV-2 can induce necrotic cell death to promote MACE in patients with ...severe COVID-19.
This observational prospective cohort study includes experiments with hamsters and human samples from patients with severe COVID-19. Cytokines and serum biomarkers were analysed in human serum. Cardiac transcriptome analyses were performed in hamsters' hearts.
From a cohort of 70 patients, MACE was documented in 26% (18/70). Those who developed MACE had higher Log copies/mL of SARS-CoV-2, troponin-I, and pro-BNP in serum. Also, the elevation of IP-10 and a major decrease in levels of IL-17ɑ, IL-6, and IL-1rɑ were observed. No differences were found in the ability of serum antibodies to neutralise viral spike proteins in pseudoviruses from variants of concern. In hamster models, we found a stark increase in viral titters in the hearts 4 days post-infection. The cardiac transcriptome evaluation resulted in the differential expression of ~ 9% of the total transcripts. Analysis of transcriptional changes in the effectors of necroptosis (mixed lineage kinase domain-like, MLKL) and pyroptosis (gasdermin D) showed necroptosis, but not pyroptosis, to be elevated. An active form of MLKL (phosphorylated MLKL, pMLKL) was elevated in hamster hearts and, most importantly, in the serum of MACE patients.
SARS-CoV-2 identification in the systemic circulation is associated with MACE and necroptosis activity. The increased pMLKL and Troponin-I indicated the occurrence of necroptosis in the heart and suggested necroptosis effectors could serve as biomarkers and/or therapeutic targets. Trial registration Not applicable.
Abstract
Background
Up to 30% of patients admitted to hospitals with invasive pneumococcal disease (IPD) experience major adverse cardiovascular event (MACE) including new/worsening heart failure, ...new/worsening arrhythmia, and/or myocardial infarction. Streptococcus pneumoniae (Spn) is the most frequently isolated bacterial pathogen among community-acquired pneumonia (CAP) patients and the only etiological agent linked independently to MACE. Nevertheless, no clinical data exist identifying which serotypes of Spn are principally responsible for MACE.
Methods
This was an observational multicenter retrospective study conducted through the Public Health Secretary of Bogotá, Colombia. We included patients with a confirmed clinical diagnosis of IPD with record of pneumococcal serotyping and clinical information between 2012 and 2019. Spn were serotyped using the quellung method by the National Center of Microbiology. MACE were determined by a retrospective chart review.
Results
The prevalence of MACE was 23% (71/310) in IPD patients and 28% (53/181) in patients admitted for CAP. The most prevalent S. pneumoniae serotype identified in our study was the 19A, responsible for the 13% (42/310) of IPD in our cohort, of which 21% (9/42) presented MACE. Serotypes independently associated with MACE in IPD patients were serotype 3 (odds ratio OR 1, 48; 95% confidence interval CI 1.21–2.27; P = .013) and serotype 9n (OR 1.29; 95% CI 1.08–2.24; P = .020). Bacteremia occurred in 87% of patients with MACE. Moreover, serum concentrations of C-reactive protein were elevated in patients with MACE versus in non-MACE patients (mean standard deviation, 138 145 vs 73 106, P = .01).
Conclusions
MACE are common during IPD with serotype 3 and 9n independently of frequency.
Major adverse cardiovascular event (MACE) is a common event during invasive pneumococcal disease (IPD) with several factors shown to have key roles in its development, including host prior cardiovascular comorbidities, disease severity, and bacteremia. Here we report for the first time that Spn serotype 3 and 9n are independently associated with the development of MACE in IPD.
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.
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.
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.
Our data highlights three distinct subpopulations in COVID-19 and CAP, with differences in inflammatory marker profiles and risks of adverse clinical outcomes.
This is a prospective study, therefore no health care intervention were applied to participants and trial registration is not applicable.
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.
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.
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.
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.
Understanding the presence and function of a diverse lung microbiome in acute lung infections, particularly ventilator-associated pneumonia (VAP), is still limited, evidencing significant gaps in our ...knowledge.
In this comprehensive narrative review, we aim to elucidate the contribution of the respiratory microbiome in the development of VAP by examining the current knowledge on the interactions among microorganisms. By exploring these intricate connections, we endeavor to enhance our understanding of the disease's pathophysiology and pave the way for novel ideas and interventions in studying the respiratory tract microbiome.
The conventional perception of lungs as sterile is deprecated since it is currently recognized the existence of a diverse microbial community within them. However, despite extensive research on the role of the respiratory microbiome in healthy lungs, respiratory chronic diseases and acute lung infections such as pneumonia are not fully understood. It is crucial to investigate further the relationship between the pathophysiology of VAP and the pulmonary microbiome, elucidating the mechanisms underlying the interactions between the microbiome, host immune response and mechanical ventilation for the development of VAP.
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
and
. In the WGS analysis, 228 isolates passed all the quality criteria and were analyzed. The principal carbapenemase-encoding gene was
KPC, specifically
KPC-2 38.6% (88/228) and
KPC-3 36.4% (83/228). These were frequently detected in co-concurrence with
VIM-2 and
NDM-1 in healthcare-acquired infections. Notably, the only identified allele among community-acquired infections was
KPC-3 50.0% (1/2). In reference to the STs, 78 were identified, of which
ST111 was mainly related to blaKPC-3.
ST512, ST258, ST14, and ST1082 were exclusively associated with
KPC-3. Finally, no particular carbapenemase-encoding gene was associated with worse clinical outcomes. The most identified genes in carbapenemase-producing Gram-negative rods were
KPC-2 and
KPC-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
, 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.
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.
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.
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).
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.
Abstract
Background
Community-acquired pneumonia (CAP) remains the first cause of infectious death and morbidity worldwide. Nevertheless, its etiological pathogen is only isolated in almost 30% of ...cases, and its most representative bacteria is S. pneumoniae. Some researchers have proposed that the nasopharyngeal colonization by S. pneumoniae could risk developing CAP. However, the prevalence of nasopharyngeal colonization in patients with chronic comorbid conditions in Latin America is unknown, where vaccination rates are low. This study aims to determine the rate of S. pneumoniae colonization in a Colombian cohort. Figure 1.Pneumococcal vaccination and colonization in the whole cohort.
Methods
This is a prospective cohort study in 3 centers in Colombia carried out between 2020 and 2022. According to the world health organization guidelines, the nasopharyngeal aspirate (NPA) samples from each participant were obtained. Samples were incubated with 5% CO2 in blood agar, and MALDI-TOFF identified the colonies obtained. We compared the number of S. pneumoniae isolated and stratified by anti-pneumococcal vaccination status.
Results
The cohort was composed of 810 patients. The median IQR age was 63 53-62 and the most common comorbidities were 52.2% 423/810 arterial hypertension, 21.7% 176/810 coronary disease, 19.0% 154/810 congestive heart failure, and 17.4% 141/810 chronic kidney disease. Nasopharyngeal colonization by S. pneumonie was only documented in the patients' 2.1% 15/723 (Figure 1). Moreover, 10.7% 87/810 patients from the cohort were vaccinated against S. pneumoniae, and none were colonized.
Conclusion
Nasopharyngeal colonization by S. pneumoniae in our cohort of adults with chronic comorbidities was low. Notably, all the colonized patients were not vaccinated, at higher risk of developing the invasive pneumococcal disease. More robust vaccination policies should be implemented for adults in Colombia.
Disclosures
All Authors: No reported disclosures.
Abstract
Background
Community-acquired pneumonia (CAP) is the principal cause of mortality due to infectious diseases globally. Some risk factors have been identified for CAP, such as age, smoking, ...environmental exposures, malnutrition, previous CAP, chronic bronchitis/chronic obstructive pulmonary disease (COPD), asthma, functional impairment, poor dental health, and immunosuppressive therapy, among others. However, these studies were conducted in high-income countries and patients without comorbid conditions. Therefore, we aimed to identify the risk factors associated with CAP development within a one-year follow-up in a prospective cohort of patients with comorbid conditions in Colombia. Table 1.Logistic Regression Analysis
Methods
This prospective cohort of adult patients with chronic comorbidities between 2020-and 2022 in Bogotá, Colombia. Univariate analysis and multivariate logistic regression model were developed to identify the variables associated with CAP development within a one-year follow-up. The logistic regression model included variables with a p-value<0.20 in the univariate analysis.
Results
A total of 810 patients were included in the program. Median IQR age was 63 53-62 and the most common comorbidities were 52.2% 423/810 arterial hypertension, 21.7% 176/810 coronary disease, and 19.0% 154/810 congestive heart failure. To date, 678 follow-ups have been made. Thirty-four patients died before the 6-month follow-up, and 46 were lost, leaving 598 patients included in the analysis. The cumulative incidence of CAP was 4.3% 26/598 during one year. After adjusting the logistic regression model, the main risk factors associated with pneumonia development were COPD OR 4.30, 95% CI 1.66-11.11, p< 0.01, and previous antibiotic treatment OR 4.08, 95% CI 1.08-15.29, p=0.04 (Table 1).
Conclusion
Patients with a history of COPD or previous antibiotic treatment have a more than 300% higher risk of developing pneumonia within one year. Robust vaccination programs for adults are needed in Colombia.
Disclosures
All Authors: No reported disclosures.
Abstract
Background
Lower respiratory tract infections (LRTI) are the leading cause of mortality and morbidity worldwide. Elderly and patients with comorbid conditions are at higher risk of ...developing LRTI and systemic complications. Therefore, the Centers for Disease Control and Prevention (CDC) and the United States National Center for Immunization and Respiratory Diseases (US-NCIRD) recommend that patients older than 19 be vaccinated for influenza annually. Patients older than 65 or with comorbid conditions (of any age) should be vaccinated for the pneumococcal vaccine. Low-middle-income countries like Colombia do not have strong policies for adults to get vaccinated. According to CDC recommendations, this study aims to determine the vaccination rate in a Colombian cohort. Figure 1.
Panel A illustrates patients’ distribution of influenza vaccine in the cohort, while Panel B shows the distribution of pneumococcal vaccine
Methods
This is the description of a prospective cohort of patients with chronic comorbid conditions between 2020-and 2022 in Bogotá, Colombia. We compared the number of patients vaccinated against Influenza and S. pneumoniae, according to CDC recommendations, to determine the adherence to international guidelines.
Results
The cohort was composed of 810 patients. The median IQR age was 63 53-62 and the most common comorbidities were 52.2% 423/810 arterial hypertension, 21.7% 176/810 coronary disease, 19.0% 154/810 congestive heart failure, and 17.4% 141/810 chronic kidney disease. According to CDC recommendations, 808 patients should have been vaccinated against influenza (Figure 1A), but only 31.7% 256/808 were immunized last year. Also, 17.8% 144/810 of the whole cohort were 65 years old and should have received the quadrivalent flu shot. Moreover, 86.4% 700/810 patients meet the criteria for pneumococcal vaccination (Figure 1B), but only 11.9% 83/700 received at least one shot.
Conclusion
Vaccination rates in our cohort of adult patients with chronic comorbidities were meager. Therefore, these patients are at higher risk of developing LRTI complications. More robust vaccination programs for adults are required in Colombia.
Disclosures
All Authors: No reported disclosures.
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