Cytokine levels as predictors of mortality in critically ill patients with severe COVID-19 pneumonia: Case-control study nested within a cohort in Colombia.

Background: High levels of different cytokines have been associated in COVID-19 as predictors of mortality; however, not all studies have found this association and its role to cause multi-organ failure and death has not been fully defined. This study aimed to investigate the association of the levels of 10 cytokines with mortality in patients with COVID-19 admitted to the intensive care unit (ICU). Materials and methods: This is a case-control study nested within a cohort of patients with COVID-19 who were on mechanical ventilation and were not hospitalized for more than 48 h across nine ICUs in Medellín, Colombia. Serum samples were collected upon admission to the ICU and 7 days later and used to measure cytokine levels. Results: Upon admission, no differences in mortality between the cytokine levels were observed when comparisons were made quantitatively. However, in the multivariate analysis, patients with median IL-1ß levels <1.365 pg/ml showed an increase in mortality (OR = 3.1; 1.24<7.71; p = 0.015). On day 7 in the ICU, IL-1ß median levels were lower (0.34 vs. 2.41 pg/ml, p = 0.042) and IL-10 higher (2.08 vs. 1.05 pg/ml, p = 0.009) in patients who died. However, in the multivariate analysis, only IL-12p70 was associated with mortality (OR = 0.23; 0.07<0.73; p = 0.012). The mean difference in the levels between day 1 and day 7 decreased in both IFN-γ (3.939 pg/ml, p < 0.039) and in IL-18 (16.312 pg/ml, p < 0.014) in the patients who died. A low IL-1ß/IL-10 ratio was associated with mortality on both day 1 and day 7, while an IL-1ß/IL-10 ratio below the cut-off on day 7 was associated with decreased survival. The lowest TNFα/IL-10 ratio was associated with mortality only on day 7. Conclusion: At the time of admission, patients with median IL-1ß levels lower than 1.365 pg/ml had increased mortality. An IL-1ß/IL-10 ratio <2 at day 7 and IL-12p70 levels >1.666 pg/ml was associated with decreased survival.

Diagnostic concordance between BioFire® FilmArray® Pneumonia Panel and culture in patients with COVID-19 pneumonia admitted to intensive care units: the experience of the third wave in eight hospitals in Colombia.

BACKGROUND: The detection of coinfections is important to initiate appropriate antimicrobial therapy. Molecular diagnostic testing identifies pathogens at a greater rate than conventional microbiology. We assessed both bacterial coinfections identified via culture or the BioFire® FilmArray® Pneumonia Panel (FA-PNEU) in patients infected with SARS-CoV-2 in the ICU and the concordance between these techniques. METHODS: This was a prospective study of patients with SARS-CoV-2 who were hospitalized for no more than 48 h and on mechanical ventilation for no longer than 24 h in 8 ICUs in Medellín, Colombia. We studied mini-bronchoalveolar lavage or endotracheal aspirate samples processed via conventional culture and the FA-PNEU. Coinfection was defined as the identification of a respiratory pathogen using the FA-PNEU or cultures. Serum samples of leukocytes, C-reactive protein, and procalcitonin were taken on the first day of intubation. We analyzed the empirical antibiotics and the changes in antibiotic management according to the results of the FA-PNEUM and cultures. RESULTS: Of 110 patients whose samples underwent both methods, FA-PNEU- and culture-positive samples comprised 24.54% versus 17.27%, respectively. Eighteen samples were positive in both techniques, 82 were negative, 1 was culture-positive with a negative FA-PNEU result, and 9 were FA-PNEU-positive with negative culture. The two bacteria most frequently detected by the FA-PNEU were Staphylococcus aureus (37.5%) and Streptococcus agalactiae (20%), and those detected by culture were Staphylococcus aureus (34.78%) and Klebsiella pneumoniae (26.08%). The overall concordance was 90.1%, and when stratified by microorganism, it was between 92.7 and 100%. The positive predictive value (PPV) was between 50 and 100% and were lower for Enterobacter cloacae and Staphylococcus aureus. The negative predictive value (NPV) was high (between 99.1 and 100%); MecA/C/MREJ had a specificity of 94.55% and an NPV of 100%. The inflammatory response tests showed no significant differences between patients whose samples were positive and negative for both techniques. Sixty-one patients (55.45%) received at least one dose of empirical antibiotics. CONCLUSIONS: The overall concordance was 90.1%, and it was between 92.7% and 100% when stratified by microorganisms. The positive predictive value was between 50 and 100%, with a very high NPV.

Strongyloidiasis in humans: diagnostic efficacy of four conventional methods and real-time polymerase chain reaction.

INTRODUCTION: Strongyloides stercoralis is an intestinal parasitic nematode that causes hyperinfection and/or a dissemination syndrome in hosts, which is often difficult to diagnose. This study aims to compare the diagnostic efficacy of four conventional methods used to diagnose strongyloidiasis with real-time polymerase chain reaction (qPCR) to detect S. stercoralis in fecal samples. METHODS: We analyzed 143 fecal samples collected from Colombian regions with varying degrees of risk for intestinal infections caused by S. stercoralis to assess the validity, performance, overall efficiency, and concordance of the qPCR using a direct stool test, modified Ritchie concentration technique, agar plate culture, and Harada-Mori technique as reference tests. RESULTS: While four fecal samples were positive for S. stercoralis using conventional methods, 32 were positive via qPCR. The diagnostic sensitivity of the qPCR was 75% [95% confidence interval (CI): 20.07-100%], whereas its specificity, negative predictive value, negative likelihood ratio, and Youden's J index were 78.42% (95% CI: 71.22-85.62%), 99.09% (95% CI: 96.86-100%), 0.32 (95% CI: 0.06-1.74), and 0.53, respectively. In addition, the estimated kappa index between the qPCR and the conventional methods was 0.12 (95% CI: -0.020-0.26). CONCLUSIONS: The diagnostic sensitivity of qPCR to detect strongyloidiasis is analogous to that of conventional parasitology methods, with an additional advantage of being capable of identifying the parasite DNA at low sample concentrations.

Strongyloidiasis in humans: diagnostic efficacy of four conventional methods and real-time polymerase chain reaction

Abstract INTRODUCTION: Strongyloides stercoralis is an intestinal parasitic nematode that causes hyperinfection and/or a dissemination syndrome in hosts, which is often difficult to diagnose. This study aims to compare the diagnostic efficacy of four conventional methods used to diagnose strongyloidiasis with real-time polymerase chain reaction (qPCR) to detect S. stercoralis in fecal samples. METHODS: We analyzed 143 fecal samples collected from Colombian regions with varying degrees of risk for intestinal infections caused by S. stercoralis to assess the validity, performance, overall efficiency, and concordance of the qPCR using a direct stool test, modified Ritchie concentration technique, agar plate culture, and Harada-Mori technique as reference tests. RESULTS While four fecal samples were positive for S. stercoralis using conventional methods, 32 were positive via qPCR. The diagnostic sensitivity of the qPCR was 75% [95% confidence interval (CI): 20.07-100%], whereas its specificity, negative predictive value, negative likelihood ratio, and Youden's J index were 78.42% (95% CI: 71.22-85.62%), 99.09% (95% CI: 96.86-100%), 0.32 (95% CI: 0.06-1.74), and 0.53, respectively. In addition, the estimated kappa index between the qPCR and the conventional methods was 0.12 (95% CI: -0.020-0.26). CONCLUSIONS: The diagnostic sensitivity of qPCR to detect strongyloidiasis is analogous to that of conventional parasitology methods, with an additional advantage of being capable of identifying the parasite DNA at low sample concentrations.

THE HUMAN MICROBIOTA: THE ROLE OF MICROBIAL COMMUNITIES IN HEALTH AND DISEASE / La microbiota humana: comunidades microbianas en la salud y en la enfermedad

During the last decade, there has been increasing awareness of the massive number of microorganisms, collectively known as the human microbiota, that are associated with humans. This microbiota outnumbers the host cells by approximately a factor of ten and contains a large repertoire of microbial genome-encoded metabolic processes. The diverse human microbiota and its associated metabolic potential can provide the host with novel functions that can influence host health and disease status in ways that still need to be analyzed. The microbiota varies with age, with features that depend on the body site, host lifestyle and health status. The challenge is therefore to identify and characterize these microbial communities and use this information to learn how they function and how they can influence the host in terms of health and well-being. Here we provide an overview of some of the recent studies involving the human microbiota and about how these communities might affect host health and disease. A special emphasis is given to studies related to tuberculosis, a disease that claims over one million lives each year worldwide and still represents a challenge for control in many countries, including Colombia.

En las últimas décadas ha incrementado nuestro conocimiento sobre la gran cantidad de microorganismos que conviven con nosotros, comunidades que colectivamente se conocen como la microbiota humana. El número de microorganismos que conforman la microbiota supera el número de células del cuerpo humano por un factor de diez aproximadamente y aporta un gran repertorio de genes y procesos metabólicos. La diversidad de la microbiota humana y su potencial metabólico brindan al hospedero una serie de funciones que complementan sus procesos y a su vez pueden influir sobre la salud del ser humano en formas que apenas se empiezan a conocer. La microbiota varía desde el nacimiento hasta la vejez del individuo, con características que dependen del sitio corporal, del estilo de vida y del estado de salud del hospedero. El reto actual es aprovechar el conocimiento derivado de la identificación y caracterización de estas comunidades microbianas para entender cómo funcionan estos microorganismos y cómo pueden influir de forma positiva o negativa sobre la salud del humano. En este documento ofrecemos una revisión general de algunos estudios recientes sobre la microbiota humana y su posible efecto en el hospedero en términos de salud y bienestar. Igualmente, se mencionan estudios sobre microbiota y su posible asociación con la tuberculosis, una enfermedad que todavía cobra más de un millón de vidas anualmente a nivel mundial y cuyo control todavía representa un gran reto en varios países del mundo, incluido Colombia.

Respiratory tract clinical sample selection for microbiota analysis in patients with pulmonary tuberculosis.

BACKGROUND: Changes in respiratory tract microbiota have been associated with diseases such as tuberculosis, a global public health problem that affects millions of people each year. This pilot study was carried out using sputum, oropharynx, and nasal respiratory tract samples collected from patients with pulmonary tuberculosis and healthy control individuals, in order to compare sample types and their usefulness in assessing changes in bacterial and fungal communities. FINDINGS: Most V1-V2 16S rRNA gene sequences belonged to the phyla Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria, and Fusobacteria, with differences in relative abundances and in specific taxa associated with each sample type. Most fungal ITS1 sequences were classified as Ascomycota and Basidiomycota, but abundances differed for the different samples. Bacterial and fungal community structures in oropharynx and sputum samples were similar to one another, as indicated by several beta diversity analyses, and both differed from nasal samples. The only difference between patient and control microbiota was found in oropharynx samples for both bacteria and fungi. Bacterial diversity was greater in sputum samples, while fungal diversity was greater in nasal samples. CONCLUSIONS: Respiratory tract microbial communities were similar in terms of the major phyla identified, yet they varied in terms of relative abundances and diversity indexes. Oropharynx communities varied with respect to health status and resembled those in sputum samples, which are collected from tuberculosis patients only due to the difficulty in obtaining sputum from healthy individuals, suggesting that oropharynx samples can be used to analyze community structure alterations associated with tuberculosis.