Louisville Coronavirus Surveillance Program

An important feature of COVID-19, the disease produced by the new coronavirus SARS-CoV-2, is the high number of health care workers (HCWs) that acquire the disease. In an initial report of 138 patients hospitalized with COVID-19 pneumonia in China, 40 patients (29%) were HCWs. One reason why HCWs are at higher risk of acquiring COVID-19 is because some patients with COVID-19 are admitted to the hospital without the classical presentation, and are therefore not tested for the disease early during hospitalization. Presently in the US, it is recommended to test for COVID-19 when physicians suspect the disease. This subjective approach may allow hospital transmission of COVID-19 from patients without the classical clinical presentation. The primary objective of this study is to establish a surveillance system for early identification of patients hospitalized with COVID-19 to allow for early implementation of infection control interventions in an attempt to prevent transmission of COVID-19 to HCWs and other hospitalized patients. We are proposing to test all patients who present to the emergency departments and/or are hospitalized with signs and symptoms of respiratory infection or gastrointestinal infection for SARS-CoV-2, regardless of clinical suspicion of COVID-19. Biological samples obtained from all patients having symptoms of respiratory or gastrointestinal infection will be tested using real-time polymerase chain reaction (RT-PCR) for detection of SARS-CoV-2. Using a robotic instrument, the CMP laboratory will be able to test more than 500 samples a day. Data will be reported in real-time to participating hospitals for rapid implementation of infection control measures

Impact of Temperature Relative Humidity and Absolute Humidity on the Incidence of Hospitalizations for Lower Respiratory Tract Infections Due to Influenza, Rhinovirus, and Respiratory Syncytial Virus: Results from Community-Acquired Pneumonia Organization (CAPO) International Cohort Study

Abstract Background: Transmissibility of several etiologies of lower respiratory tract infections (LRTI) may vary based on outdoor climate factors. The objective of this study was to evaluate the impact of outdoor temperature, relative humidity, and absolute humidity on the incidence of hospitalizations for lower respiratory tract infections due to influenza, rhinovirus, and respiratory syncytial virus (RSV). Methods: This was a secondary analysis of an ancillary study of the Community Acquired Pneumonia Organization (CAPO) database. Respiratory viruses were detected using the Luminex xTAG respiratory viral panel. Climate factors were obtained from the National Weather Service. Adjusted Poisson regression models with robust error variance were used to model the incidence of hospitalization with a LRTI due to: 1) influenza, 2) rhinovirus, and 3) RSV (A and/or B), separately. Results: A total of 467 hospitalized patients with LRTI were included in the study; 135 (29%) with influenza, 41 (9%) with rhinovirus, and 27 (6%) with RSV (20 RSV A, 7 RSV B). The average, minimum, and maximum absolute humidity and temperatur e variables were associated with hospitalization due to influenza LRTI, while the relative humidity variables were not. None of the climate variables were associated with hospitalization due to rhinovirus or RSV. Conclusions: This study suggests that outdoor absolute humidity and temperature are associated with hospitalizations due to influenza LRTIs, but not with LRTIs due to rhinovirus or RSV. Understanding factors contributing to the transmission of respiratory viruses may assist in the prediction of future outbreaks and facilitate the development of transmission prevention interventions

Identification by Real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues

PURPOSE: Diffuse large B-cell lymphoma (DLBCL) heterogeneity has prompted investigations for new biomarkers that can accurately predict survival. A previously reported 6-gene model combined with the International Prognostic Index (IPI) could predict patients' outcome. However, even these predictors are not capable of unambiguously identifying outcome, suggesting that additional biomarkers might improve their predictive power. EXPERIMENTAL DESIGN: We studied expression of 11 microRNAs (miRNA) that had previously been reported to have variable expression in DLBCL tumors. We measured the expression of each miRNA by quantitative real-time PCR analyses in 176 samples from uniformly treated DLBCL patients and correlated the results to survival. RESULTS: In a univariate analysis, the expression of miR-18a correlated with overall survival (OS), whereas the expression of miR-181a and miR-222 correlated with progression-free survival (PFS). A multivariate Cox regression analysis including the IPI, the 6-gene model-derived mortality predictor score and expression of the miR-18a, miR-181a, and miR-222, revealed that all variables were independent predictors of survival except the expression of miR-222 for OS and the expression of miR-18a for PFS. CONCLUSION: The expression of specific miRNAs may be useful for DLBCL survival prediction and their role in the pathogenesis of this disease should be examined further

Endemic Human Coronaviruses in Hospitalized Adults with Community-Acquired Pneumonia: Results from the Louisville Pneumonia Study

Introduction: There are four endemic serotypes of human coronavirus (HCoV) that may cause community-acquired pneumonia (CAP) in humans. The clinical syndrome of CAP due to HCoVs is not well characterized. The objectives of this study were to evaluate incidence, epidemiology, and outcomes of CAP in adults due to HCoV and to compare them with CAP due to influenza. Methods: The Louisville Pneumonia Study (LPS) is a prospective observational study of hospitalized adult patients with CAP in the city of Louisville. Patients enrolled in the LPS in whom a respiratory viral panel polymerase chain reaction (PCR) was obtained were evaluated. Incidence, epidemiology, and outcomes were compared for patients with a positive PCR for HCoV versus patients with a positive PCR for influenza. Results: From 1,974 CAP patients with a PCR performed, HCoV was identified in 65 patients (3.3%), corresponding to the following serotypes: HCoV-229E in 12 patients, HCoV-OC43 in 38 patients, HCoV-NL63 in 6 patients and HCoV-HKU1 in 9 patients. No differences were observed in clinical presentation and early outcomes for patients with CAP due to HCoV compared to 244 patients with CAP due to influenza. One-year mortality after hospitalization was 32% for patients with CAP due to HCoV versus 13% for patients with CAP due to influenza. Conclusions: When compared to patients with CAP due to influenza, the clinical presentation of patients with CAP due to HCoV is similar, but these patients have significantly worse outcomes one year after hospitalization

Community-Acquired Pneumonia due to Endemic Human Coronaviruses compared to 2019 Novel Coronavirus: A Review

The human coronaviruses (HCoVs) are an important etiology of community-acquired respiratory tract infections. Community-acquired pneumonia (CAP) may be caused by serotypes of endemic HCoVs or highly pathogenic HCoVs. In this review we compared the clinical characteristic, management, outcomes, and infection control practices for patients with CAP due to endemic HCoVs versus patients with CAP due to 2019 novel coronavirus

Genome-wide association study of height-adjusted BMI in childhood identifies functional variant in ADCY3

Objective: Genome-wide association studies (GWAS) of BMI are mostly undertaken under the assumption that "kg/m2" is an index of weight fully adjusted for height, but in general this is not true. The aim here was to assess the contribution of common genetic variation to a adjusted version of that phenotype which appropriately accounts for covariation in height in children. Methods: A GWAS of height-adjusted BMI (BMI[x]=weight/heightx), calculated to be uncorrelated with height, in 5809 participants (mean age 9.9 years) from the Avon Longitudinal Study of Parents and Children (ALSPAC) was performed. Results: GWAS based on BMI[x] yielded marked differences in genomewide results profile. SNPs in ADCY3 (adenylate cyclase 3) were associated at genome-wide significance level (rs11676272 (0.28 kg/m3.1 change per allele G (0.19, 0.38), P=6 × 10-9). In contrast, they showed marginal evidence of association with conventional BMI [rs11676272 (0.25 kg/m2 (0.15, 0.35), P=6 × 10-7)]. Results were replicated in an independent sample, the Generation R study. Conclusions: Analysis of BMI[x] showed differences to that of conventional BMI. The association signal at ADCY3 appeared to be driven by a missense variant and it was strongly correlated with expression of this gene. Our work highlights the importance of well understood phenotype use (and the danger of convention) in characterising genetic contributions to complex traits

Prevalence of sexual dimorphism in mammalian phenotypic traits.

The role of sex in biomedical studies has often been overlooked, despite evidence of sexually dimorphic effects in some biological studies. Here, we used high-throughput phenotype data from 14,250 wildtype and 40,192 mutant mice (representing 2,186 knockout lines), analysed for up to 234 traits, and found a large proportion of mammalian traits both in wildtype and mutants are influenced by sex. This result has implications for interpreting disease phenotypes in animal models and humans

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN