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COVID-19 bacteremic co-infection is a major risk factor for mortality, ICU admission, and mechanical ventilation
Background
Recent single-center reports have suggested that community-acquired bacteremic co-infection in the context of Coronavirus disease 2019 (COVID-19) may be an important driver of mortality; however, these reports have not been validated with a multicenter, demographically diverse, cohort study with data spanning the pandemic.
Methods
In this multicenter, retrospective cohort study, inpatient encounters were assessed for COVID-19 with community-acquired bacteremic co-infection using 48-h post-admission blood cultures and grouped by: (1) confirmed co-infection [recovery of bacterial pathogen], (2) suspected co-infection [negative culture with ≥ 2 antimicrobials administered], and (3) no evidence of co-infection [no culture]. The primary outcomes were in-hospital mortality, ICU admission, and mechanical ventilation. COVID-19 bacterial co-infection risk factors and impact on primary outcomes were determined using multivariate logistic regressions and expressed as adjusted odds ratios with 95% confidence intervals (Cohort, OR 95% CI, Wald test
p
value).
Results
The studied cohorts included 13,781 COVID-19 inpatient encounters from 2020 to 2022 in the University of Alabama at Birmingham (UAB,
n
= 4075) and Ochsner Louisiana State University Health—Shreveport (OLHS,
n
= 9706) cohorts with confirmed (2.5%), suspected (46%), or no community-acquired bacterial co-infection (51.5%) and a comparison cohort consisting of 99,170 inpatient encounters from 2010 to 2019 (UAB pre-COVID-19 pandemic cohort). Significantly increased likelihood of COVID-19 bacterial co-infection was observed in patients with elevated ≥ 15 neutrophil-to-lymphocyte ratio (UAB: 1.95 [1.21–3.07]; OLHS: 3.65 [2.66–5.05],
p
< 0.001 for both) within 48-h of hospital admission. Bacterial co-infection was found to confer the greatest increased risk for in-hospital mortality (UAB: 3.07 [2.42–5.46]; OLHS: 4.05 [2.29–6.97],
p
< 0.001 for both), ICU admission (UAB: 4.47 [2.87–7.09], OLHS: 2.65 [2.00–3.48],
p
< 0.001 for both), and mechanical ventilation (UAB: 3.84 [2.21–6.12]; OLHS: 2.75 [1.87–3.92],
p
< 0.001 for both) across both cohorts, as compared to other risk factors for severe disease. Observed mortality in COVID-19 bacterial co-infection (24%) dramatically exceeds the mortality rate associated with community-acquired bacteremia in pre-COVID-19 pandemic inpatients (5.9%) and was consistent across alpha, delta, and omicron SARS-CoV-2 variants.
Conclusions
Elevated neutrophil-to-lymphocyte ratio is a prognostic indicator of COVID-19 bacterial co-infection within 48-h of admission. Community-acquired bacterial co-infection, as defined by blood culture-positive results, confers greater increased risk of in-hospital mortality, ICU admission, and mechanical ventilation than previously described risk factors (advanced age, select comorbidities, male sex) for COVID-19 mortality, and is independent of SARS-CoV-2 variant.
Journal Article
Mapping the evolving definitions of translational research
Systematic review and analysis of definitions of translational research.
The final corpus was comprised of 33 papers, each read by at least 2 reviewers. Definitions were mapped to a common set of research processes for presentation and analysis. Influence of papers and definitions was further evaluated using citation analysis and agglomerative clustering.
All definitions were mapped to common research processes, revealing most common labels for each process. Agglomerative clustering revealed 3 broad families of definitions. Citation analysis showed that the originating paper of each family has been cited ~10 times more than any other member.
Although there is little agreement between definitions, we were able to identify an emerging consensus 5-phase (T0-T4) definition for translational research. T1 involves processes that bring ideas from basic research through early testing in humans. T2 involves the establishment of effectiveness in humans and clinical guidelines. T3 primarily focuses on implementation and dissemination research while T4 focuses on outcomes and effectiveness in populations. T0 involves research such as genome-wide association studies which wrap back around to basic research.
We used systematic review and analysis to identify emerging consensus between definitions of translational research phases.
Journal Article
Seroprevalence of SARS-CoV-2 and Infection Fatality Ratio, Orleans and Jefferson Parishes, Louisiana, USA, May 2020
Using a novel recruitment method and paired molecular and antibody testing for severe acute respiratory syndrome coronavirus 2 infection, we determined seroprevalence in a racially diverse municipality in Louisiana, USA. Infections were highly variable by ZIP code and differed by race/ethnicity. Overall census-weighted seroprevalence was 6.9%, and the calculated infection fatality ratio was 1.63%.
Journal Article
Racial and Workplace Disparities in Seroprevalence of SARS-CoV-2, Baton Rouge, Louisiana, USA
By using paired molecular and antibody testing for severe acute respiratory syndrome coronavirus 2 infection, we determined point prevalence and seroprevalence in Louisiana, USA, during the second phase of reopening. Infections were highly variable by race and ethnicity, work environment, and ZIP code. Census-weighted seroprevalence was 3.6%, and point prevalence was 3.0%.
Journal Article
Establishing a framework for privacy-preserving record linkage among electronic health record and administrative claims databases within PCORnet®, the National Patient-Centered Clinical Research Network
Objective
The aim of this study was to determine whether a secure, privacy-preserving record linkage (PPRL) methodology can be implemented in a scalable manner for use in a large national clinical research network.
Results
We established the governance and technical capacity to support the use of PPRL across the National Patient-Centered Clinical Research Network (PCORnet
®
). As a pilot, four sites used the Datavant software to transform patient personally identifiable information (PII) into de-identified tokens. We queried the sites for patients with a clinical encounter in 2018 or 2019 and matched their tokens to determine whether overlap existed. We described patient overlap among the sites and generated a “deduplicated” table of patient demographic characteristics. Overlapping patients were found in 3 of the 6 site-pairs. Following deduplication, the total patient count was 3,108,515 (0.11% reduction), with the largest reduction in count for patients with an “Other/Missing” value for Sex; from 198 to 163 (17.6% reduction). The PPRL solution successfully links patients across data sources using distributed queries without directly accessing patient PII. The overlap queries and analysis performed in this pilot is being replicated across the full network to provide additional insight into patient linkages among a distributed research network.
Journal Article
A bioinformatic analysis of T-cell epitope diversity in SARS-CoV-2 variants: association with COVID-19 clinical severity in the United States population
Long-term immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires the identification of T-cell epitopes affecting host immunogenicity. In this computational study, we explored the CD8 + epitope diversity estimated in 27 of the most common HLA-A and HLA-B alleles, representing most of the United States population. Analysis of 16 SARS-CoV-2 variants [B.1, Alpha (B.1.1.7), five Delta (AY.100, AY.25, AY.3, AY.3.1, AY.44), and nine Omicron (BA.1, BA.1.1, BA.2, BA.4, BA.5, BQ.1, BQ.1.1, XBB.1, XBB.1.5)] in analyzed MHC class I alleles revealed that SARS-CoV-2 CD8 + epitope conservation was estimated at 87.6%–96.5% in spike (S), 92.5%–99.6% in membrane (M), and 94.6%–99% in nucleocapsid (N). As the virus mutated, an increasing proportion of S epitopes experienced reduced predicted binding affinity: 70% of Omicron BQ.1-XBB.1.5 S epitopes experienced decreased predicted binding, as compared with ~3% and ~15% in the earlier strains Delta AY.100–AY.44 and Omicron BA.1–BA.5, respectively. Additionally, we identified several novel candidate HLA alleles that may be more susceptible to severe disease, notably HLA-A*32:01 , HLA-A*26:01 , and HLA-B*53:01 , and relatively protected from disease, such as HLA-A*31:01 , HLA-B*40:01 , HLA-B*44:03 , and HLA-B*57:01. Our findings support the hypothesis that viral genetic variation affecting CD8 T-cell epitope immunogenicity contributes to determining the clinical severity of acute COVID-19. Achieving long-term COVID-19 immunity will require an understanding of the relationship between T cells, SARS-CoV-2 variants, and host MHC class I genetics. This project is one of the first to explore the SARS-CoV-2 CD8 + epitope diversity that putatively impacts much of the United States population.
Journal Article
Prediagnostic plasma nutrimetabolomics and prostate cancer risk: a nested case–control analysis within the EPIC study
Background and Objective: Nutrimetabolomics may reveal novel insights into early metabolic alterations and the role of dietary exposures on prostate cancer (PCa) risk. We aimed to prospectively investigate the associations between plasma metabolite concentrations and PCa risk, including clinically relevant tumor subtypes. Methods: We used a targeted and large-scale metabolomics approach to analyze plasma samples of 851 matched PCa case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Associations between metabolite concentrations and PCa risk were estimated by multivariate conditional logistic regression analysis. False discovery rate (FDR) was used to control for multiple testing correction. Results: Thirty-one metabolites (predominately derivatives of food intake and microbial metabolism) were associated with overall PCa risk and its clinical subtypes (p < 0.05), but none of the associations exceeded the FDR threshold. The strongest positive and negative associations were for dimethylglycine (OR = 2.13; 95% CI 1.16-3.91) with advanced PCa risk (n = 157) and indole-3-lactic acid (OR = 0.28; 95% CI 0.09-0.87) with fatal PCa risk (n = 57), respectively; however, these associations did not survive correction for multiple testing. Conclusions: The results from the current nutrimetabolomics study suggest that apart from early metabolic deregulations, some biomarkers of food intake might be related to PCa risk, especially advanced and fatal PCa. Further independent and larger studies are needed to validate our results.
Journal Article
Intake of the total, classes, and subclasses of (poly)phenols and risk of prostate cancer: a prospective analysis of the epic study
The study was supported by grant 553/C/2019 funded by La Marató de TV-3; grant PID2020-114921RB-C21 funded by MCIN/AEI/10.13039/501100011033, grants PI18/0191 and PI22/0412, and CIBERFES (CB16/10/00269), from the Institute of Health Carlos III, all of them co-funded by European Regional Development Fund “ERDF”, a way to build Europe. The Generalitat de Catalunya’s Agency AGAUR of 2021SGR00687. Maria de Maeztu Unit of Excellence grant (CEX2021-001234-M) funded by (MICIN/AEI/FEDER, UE). The PANACEA project was funded by the European Union, in the framework of the Public Health Programme (project number: 2005328)
Journal Article