Nasopharyngeal Microbiota as an early severity biomarker in COVID-19 hospitalised patients: a retrospective cohort study in a Mediterranean area.
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ABSTRACT:
SUBMITTER: Ventero MP
PROVIDER: S-EPMC8709923 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Little is known about the relationship between the specific airway microbiota composition and severity of bronchiolitis. We aimed to identify nasopharyngeal microbiota profiles and link these profiles to acute severity in infants hospitalised for bronchiolitis.We conducted a multicentre prospective cohort study of 1005 infants (age <1?year) hospitalised for bronchiolitis over three winters, 2011-2014. By applying a 16S rRNA gene sequence and clustering approach to the nasopharyngeal aspirates collected within 24?h of hospitalisation, we determined nasopharyngeal microbiota profiles and their association with bronchiolitis severity. The primary outcome was intensive care use, i.e. admission to an intensive care unit or use of mechanical ventilation.We identified four nasopharyngeal microbiota profiles: three profiles were dominated by one of Haemophilus, Moraxella or Streptococcus, while the fourth profile had the highest bacterial richness. The rate of intensive care use was highest in infants with a Haemophilus-dominant profile and lowest in those with a Moraxella-dominant profile (20.2% versus 12.3%; unadjusted OR 1.81, 95% CI 1.07-3.11, p=0.03). After adjusting for 11 patient-level confounders, the rate remained significantly higher in infants with Haemophilus-dominant profiles (OR 1.98, 95% CI 1.08-3.62, p=0.03). These findings were externally validated in a separate cohort of 307 children hospitalised for bronchiolitis.
| S-EPMC5459592 | biostudies-literature
Project description:Early life respiratory microbiota may increase risk for future pulmonary disease. Associations between respiratory microbiota and lung health in children from low- and middle-income countries are not well-described. Leveraging the Ghana Randomized Air Pollution and Health Study (GRAPHS) prospective pregnancy cohort in Kintampo, Ghana, we collected nasopharyngeal swabs in 112 asymptomatic children aged median 4.3 months (interquartile range (IQR) 2.9, 7.1) and analyzed 22 common bacterial and viral pathogens with MassTag polymerase chain reaction (PCR). We prospectively followed the cohort and measured lung function at age four years by impulse oscillometry. First, we employed latent class analysis (LCA) to identify nasopharyngeal microbiota (NPM) subphenotypes. Then, we used linear regression to analyze associations between subphenotype assignment and lung function. LCA suggest that a two-class model best described the infant NPM. We identified a higher diversity subphenotype (N = 38, 34%) with more pathogens (median 4; IQR 3.25, 4.75) and a lower diversity subphenotype (N = 74, 66%) with fewer pathogens (median 1; IQR 1, 2). In multivariable linear regression models, the less diverse NPM subphenotype had higher small airway resistance (R5-R20 β = 17.9%, 95% CI 35.6, 0.23; p = 0.047) compared with the more diverse subphenotype. Further studies are required to understand the role of the microbiota in future lung health.
| S-EPMC8305530 | biostudies-literature
Project description:Rationale: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and hospitalizations in infants worldwide. Known risk factors, however, incompletely explain the variability of RSV disease severity among children. We postulate that severity of RSV infection is influenced in part by modulation of the host immune response by the local microbial ecosystem at the time of infection. Objectives: To define whether different nasopharyngeal microbiota profiles are associated with distinct host transcriptome profiles and severity in children with RSV infection. Methods: We analyzed the nasopharyngeal microbiota profiles of young children with mild and severe RSV disease and healthy matched controls by 16S-rRNA sequencing. In parallel, we analyzed whole blood gene expression profiles to study the relationship between microbial community composition, the RSV-induced host transcriptional response and clinical disease severity. Measurements and Main results: We identified five nasopharyngeal microbiota profiles characterized by enrichment of H. influenzae, Streptococcus, Corynebacterium, Moraxella or S. aureus. RSV infection and RSV hospitalization were positively associated with H. influenzae and Streptococcus, and negatively associated with S. aureus abundance, independent of age. The host response to RSV was defined by overexpression of interferon-related genes, and this was independent of the microbiota composition. On the other hand, transcriptome profiles of RSV infected children with H. influenzae and Streptococcus-dominated microbiota were characterized by greater overexpression of genes linked to toll-like receptor-signaling and neutrophil activation and were more frequently hospitalized Conclusions: Our data suggest an immunomodulatory role for the resident nasopharyngeal microbial community early in RSV infection, potentially affecting RSV disease severity.
2016-05-09 | GSE77087 | GEO
Project description:Emerging evidence suggests that the airway microbiota plays an important role in viral bronchiolitis pathobiology. However, little is known about the combined role of airway microbiota and CCL5 in infants with bronchiolitis. In this multicenter prospective cohort study of 1005 infants (age <1 year) hospitalized for bronchiolitis during 2011-2014, we observed statistically significant interactions between nasopharyngeal airway CCL5 levels and microbiota profiles with regard to the risk of both intensive care use (Pinteraction =.02) and hospital length-of-stay ?3 days (Pinteraction =.03). Among infants with lower CCL5 levels, the Haemophilus-dominant microbiota profile was associated with a higher risk of intensive care use (OR, 3.20; 95%CI, 1.18-8.68; P=.02) and hospital length-of-stay ?3 days (OR, 4.14; 95%CI, 2.08-8.24; P<.001) compared to the Moraxella-dominant profile. Conversely, among those with higher CCL5 levels, there were no significant associations between the microbiota profiles and these severity outcomes (all P?.10).
| S-EPMC5601014 | biostudies-literature
Project description:RationaleRespiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and hospitalizations in infants worldwide. Known risk factors, however, incompletely explain the variability of RSV disease severity, especially among healthy children. We postulate that the severity of RSV infection is influenced by modulation of the host immune response by the local bacterial ecosystem.ObjectivesTo assess whether specific nasopharyngeal microbiota (clusters) are associated with distinct host transcriptome profiles and disease severity in children less than 2 years of age with RSV infection.MethodsWe characterized the nasopharyngeal microbiota profiles of young children with mild and severe RSV disease and healthy children by 16S-rRNA sequencing. In parallel, using multivariable models, we analyzed whole-blood transcriptome profiles to study the relationship between microbial community composition, the RSV-induced host transcriptional response, and clinical disease severity.Measurements and main resultsWe identified five nasopharyngeal microbiota clusters characterized by enrichment of either Haemophilus influenzae, Streptococcus, Corynebacterium, Moraxella, or Staphylococcus aureus. RSV infection and RSV hospitalization were positively associated with H. influenzae and Streptococcus and negatively associated with S. aureus abundance, independent of age. Children with RSV showed overexpression of IFN-related genes, independent of the microbiota cluster. In addition, transcriptome profiles of children with RSV infection and H. influenzae- and Streptococcus-dominated microbiota were characterized by greater overexpression of genes linked to Toll-like receptor and by neutrophil and macrophage activation and signaling.ConclusionsOur data suggest that interactions between RSV and nasopharyngeal microbiota might modulate the host immune response, potentially affecting clinical disease severity.
| S-EPMC5114450 | biostudies-literature
Project description:The aims of our study was compare adherence measured by the medical possession ratio (MPR), time until discontinuation and describe adverse events after adding a DPP-4i, SGLT-2i, or sulfonylureas (SU) to metformin in a primary care population with insufficient glycemic control. We used routinely-collected health data from the SIDIAP database. The included subjects were matched by propensity score. The follow-up period was up to 24 months or premature discontinuation. The primary outcomes were the percentage of subjects with good adherence, treatment discontinuation and adverse events among treatment groups. The proportion of patients with good adherence (MPR> 0.8) after the addition of DPP-4i, SGLT-2i or SU was 53.6%, 68.7%, and 43.0%, respectively. SGLT-2i users were 1.7 times more likely to achieve good adherence compared with DPP-4i users (odds ratio [OR]:1.72, 98% confidence interval [CI]:1.51, 1.96), and 2.8 times more likely compared with SU users (OR: 0.35, 98% CI: 0.07, 0.29). The discontinuation hazard ratios were 1.43 (98%CI: 1.26; 1.62) and 1.60 (98%CI: 1.42; 1.81) times higher among SGLT-2i and SU users than DPP-4i users during the follow-up period. No differences were observed for adverse events among the treatment groups. In conclusion, in our real-world setting, the combination of SGLT-2i with metformin was associated with better adherence. The mean time until discontinuation was longer in the SGLT-2i group in comparison with the DPP-4i or SU groups.
| S-EPMC8318034 | biostudies-literature
Project description:ObjectiveTo report the clinical characteristics of patients hospitalised with COVID-19 in Southeast Michigan.DesignRetrospective cohort study.SettingEight hospitals in Southeast Michigan.Participants3219 hospitalised patients with a positive SARS-CoV-2 infection by nasopharyngeal PCR test from 13 March 2020 until 29 April 2020.Main outcomes measuresOutcomes were discharge from the hospital or in-hospital death. Examined predictors included patient demographics, chronic diseases, home medications, mechanical ventilation, in-hospital medications and timeframe of hospital admission. Multivariable logistic regression was conducted to identify risk factors for in-hospital mortality.ResultsDuring the study period, 3219 (90.4%) patients were discharged or died in the hospital. The median age was 65.2 (IQR 52.6-77.2) years, the median length of stay in the hospital was 6.0 (IQR 3.2-10.1) days, and 51% were female. Hypertension was the most common chronic disease, occurring in 2386 (74.1%) patients. Overall mortality rate was 16.0%. Blacks represented 52.3% of patients and had a mortality rate of 13.5%. Mortality was highest at 18.5% in the prepeak hospital COVID-19 volume, decreasing to 15.3% during the peak period and to 10.8% in the postpeak period. Multivariable regression showed increasing odds of in-hospital death associated with older age (OR 1.04, 95% CI 1.03 to 1.05, p<0.001) for every increase in 1 year of age and being male (OR 1.47, 95% CI 1.21 to 1.81, p<0.001). Certain chronic diseases increased the odds of in-hospital mortality, especially chronic kidney disease. Administration of vitamin C, corticosteroids and therapeutic heparin in the hospital was associated with higher odds of death.ConclusionIn-hospital mortality was highest in early admissions and improved as our experience in treating patients with COVID-19 increased. Blacks were more likely to get admitted to the hospital and to receive mechanical ventilation, but less likely to die in the hospital than whites.
| S-EPMC8029036 | biostudies-literature
Project description:BackgroundEmerging evidence suggests relationships between the nasopharyngeal metabolome and both the microbiota and severity of bronchiolitis. However, the influence of host systemic metabolism on disease pathobiology remains unclear. We aimed to examine metabolome profiles and their association with more-severe disease, defined by use of positive pressure ventilation (PPV), in infants hospitalized for bronchiolitis.MethodsIn 140 infants with bronchiolitis, metabolomic profiling was performed on serum; samples from 70 were in a training data set, and samples from 70 were in an independent test data set. We also profiled the nasopharyngeal airway microbiota and examined its association with the serum metabolites.ResultsSerum metabolome profiles differed by bronchiolitis severity (P < .001). In total, 20 metabolites in the training data set were significantly associated with the risk of PPV, of which 18 remained significant following adjustment for confounders (false-discovery rate [FDR], < 0.10). Phosphatidylcholine metabolites were associated with higher risks of PPV use, while metabolites from the plasmalogen subpathway were associated with lower risks. The test data set validated these findings (FDR < 0.05). Streptococcus abundance was positively associated with metabolites that are associated with higher risks of PPV.ConclusionsSerum metabolomic signatures were associated with both the nasopharyngeal microbiota and the severity of bronchiolitis. Our findings advance research into the complex interrelations between the airway microbiome, host systemic response, and pathobiology of bronchiolitis.
| S-EPMC6534192 | biostudies-literature
Project description:Diabetes is a risk factor for developing severe COVID-19, but the pathogenesis remains unclear. We investigated if the association of diabetes and COVID-19 severity may be mediated by inflammation. We also hypothesized that this increased risk may extend to prediabetes. Hospitalized patients in Singapore with COVID-19 were subdivided into three groups in a retrospective cohort: normoglycemia (HbA1c: ≤5.6%), prediabetes (HbA1c: 5.7%-6.4%) and diabetes (HbA1c: ≥6.5%). The primary outcome of severe COVID-19 was defined by respiratory rate ≥30, SpO2 ≤93% or intensive care unit admission. The association between clinical factors on severe COVID-19 outcome was analyzed by cox regression. Adjusted mediation analysis of C-reactive protein (CRP) on the relationship between diabetes and severe COVID-19 was performed. Of 1042 hospitalized patients, mean age 39 ± 11 years, 13% had diabetes, 9% prediabetes and 78% normoglycemia. Severe COVID-19 occurred in 4.9% of subjects. Compared to normoglycemia, diabetes was significantly associated with severe COVID-19 on both univariate (hazard ratio [HR]: 9.94; 95% confidence interval [CI]: 5.54-17.84; p < .001) and multivariate analysis (HR: 3.99; 95% CI: 1.92-8.31; p < .001), while prediabetes was not a risk factor (HR: 0.94; 95% CI: 0.22-4.03; p = .929). CRP, a biomarker of inflammation, mediated 32.7% of the total association between diabetes and severe COVID-19 outcome. In conclusion, CRP is a partial mediator of the association between diabetes and severe COVID-19 infection, confirming that inflammation is important in the pathogenesis of severe COVID-19 in diabetes.
| S-EPMC8013709 | biostudies-literature
Project description:BackgroundType 2 diabetes and obesity, as states of chronic inflammation, are risk factors for severe COVID-19. Metformin has cytokine-reducing and sex-specific immunomodulatory effects. Our aim was to identify whether metformin reduced COVID-19-related mortality and whether sex-specific interactions exist.MethodsIn this retrospective cohort analysis, we assessed de-identified claims data from UnitedHealth Group (UHG)'s Clinical Discovery Claims Database. Patient data were eligible for inclusion if they were aged 18 years or older; had type 2 diabetes or obesity (defined based on claims); at least 6 months of continuous enrolment in 2019; and admission to hospital for COVID-19 confirmed by PCR, manual chart review by UHG, or reported from the hospital to UHG. The primary outcome was in-hospital mortality from COVID-19. The independent variable of interest was home metformin use, defined as more than 90 days of claims during the year before admission to hospital. Covariates were comorbidities, medications, demographics, and state. Heterogeneity of effect was assessed by sex. For the Cox proportional hazards, censoring was done on the basis of claims made after admission to hospital up to June 7, 2020, with a best outcome approach. Propensity-matched mixed-effects logistic regression was done, stratified by metformin use.Findings6256 of the 15 380 individuals with pharmacy claims data from Jan 1 to June 7, 2020 were eligible for inclusion. 3302 (52·8%) of 6256 were women. Metformin use was not associated with significantly decreased mortality in the overall sample of men and women by either Cox proportional hazards stratified model (hazard ratio [HR] 0·887 [95% CI 0·782-1·008]) or propensity matching (odds ratio [OR] 0·912 [95% CI 0·777-1·071], p=0·15). Metformin was associated with decreased mortality in women by Cox proportional hazards (HR 0·785, 95% CI 0·650-0·951) and propensity matching (OR 0·759, 95% CI 0·601-0·960, p=0·021). There was no significant reduction in mortality among men (HR 0·957, 95% CI 0·82-1·14; p=0·689 by Cox proportional hazards).InterpretationMetformin was significantly associated with reduced mortality in women with obesity or type 2 diabetes who were admitted to hospital for COVID-19. Prospective studies are needed to understand mechanism and causality. If findings are reproducible, metformin could be widely distributed for prevention of COVID-19 mortality, because it is safe and inexpensive.FundingNational Heart, Lung, and Blood Institute; Agency for Healthcare Research and Quality; Patient-Centered Outcomes Research Institute; Minnesota Learning Health System Mentored Training Program, M Health Fairview Institutional Funds; National Center for Advancing Translational Sciences; and National Cancer Institute.
| S-EPMC7832552 | biostudies-literature