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PUBMED; 2020.
Preprint in English | PUBMED | ID: ppcovidwho-292827


The recent outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has led to a worldwide pandemic. One week after initial symptoms develop, a subset of patients progresses to severe disease, with high mortality and limited treatment options. To design novel interventions aimed at preventing spread of the virus and reducing progression to severe disease, detailed knowledge of the cell types and regulating factors driving cellular entry is urgently needed. Here we assess the expression patterns in genes required for COVID-19 entry into cells and replication, and their regulation by genetic, epigenetic and environmental factors, throughout the respiratory tract using samples collected from the upper (nasal) and lower airways (bronchi). Matched samples from the upper and lower airways show a clear increased expression of these genes in the nose compared to the bronchi and parenchyma. Cellular deconvolution indicates a clear association of these genes with the proportion of secretory epithelial cells. Smoking status was found to increase the majority of COVID-19 related genes including ACE2 and TMPRSS2 but only in the lower airways, which was associated with a significant increase in the predicted proportion of goblet cells in bronchial samples of current smokers. Both acute and second hand smoke were found to increase ACE2 expression in the bronchus. Inhaled corticosteroids decrease ACE2 expression in the lower airways. No significant effect of genetics on ACE2 expression was observed, but a strong association of DNA- methylation with ACE2 and TMPRSS2- mRNA expression was identified in the bronchus.

American Journal of Respiratory and Critical Care Medicine ; 203(9):1, 2021.
Article in English | Web of Science | ID: covidwho-1407147
American Journal of Respiratory and Critical Care Medicine ; 203(9):1, 2021.
Article in English | Web of Science | ID: covidwho-1406930
American Journal of Respiratory and Critical Care Medicine ; 203(9), 2021.
Article in English | EMBASE | ID: covidwho-1277563


Rationale: D-dimer is primarily used in the diagnosis of venous thromboembolic (VTE) disease. Recently the Ddimer test has been used as a marker of inflammation in COVID-19 pneumonia and has been shown to correlate with worse outcomes. An understanding of trajectories and relation to clot burden and outcomes of this novel use of serial measurements of D-dimer in COVID-19 ICU patients remains to be explored. Methods: We reviewed patients who were admitted to the Northwestern Hospital COVID ICUs from 3/1/20 to 7/31/20. We obtained demographics, d-dimer lab values, venous duplex studies from upper and lower extremities (UE/LE dopplers), CT-angiogram (CTA) reports, and mortality outcomes from our electronic medical record database. Reports were processed using string analysis with manual physician validation. Analysis was done in R with nonparametric numeric variables being compared by two-tailed Mann Whitney tests. Results: We had 370 patients in our cohort, with median (interquartile range (IQR)) age being 60 (49-69), 229/370 (62%) male, 128 (35%) of Hispanic ethnicity, 117 (32%) of African-American ethnicity, and 135 (36%) of Caucasian descent. 70 patients died (19%). The total number of VTE imaging tests included: 87 CTAs, 102 UE dopplers, and 232 LE dopplers. Clot was discovered in 43/102 (42%) UE dopplers, 62/232 (27%) of LE dopplers, and 25/87 (29%) of CTAs. Patients underwent a median of 2 (1-3) imaging studies, and 10 (4-20) d-dimer measurements. 79 unique patients (21%) had VTE detected. There was no statistically significant difference in age between the clot vs noclot groups: 57(45-68) vs 61(49-59) years, p=0.34, or BMI: 30.5(25.6-34.8) in clot vs 29(25.4-34.5) kg/m2 in no-clot group (p=0.55). Mortality was significantly higher at 36% in the clot group vs 15% in the group without clot (p<0.005). Hospital length of stay in the group with clot was significantly longer at 30.5(20.3-43.5) days vs no-clot 14(7.9-18.5) days (p<0.0001). The clot group had higher initial d-dimer values 2,236(752-3,654) ng/ml than the no-clot group 757(395-1,940) (p<0.0001), and also higher peak d-dimer values 9,476(3,353-16,595) vs 2,113(686-3,689) ng/ml (p<0.0001). Conclusion: Critically ill COVID-19 patients exhibit a high rate of clot formation. Here we describe a cohort of ICU patients with COVID-19 and their demographics, d-dimer trends, clot burden, and outcomes. Future studies will focus on predictors of clot presence and outcomes based on ddimer trends.

American Journal of Respiratory and Critical Care Medicine ; 203(9), 2021.
Article in English | EMBASE | ID: covidwho-1277173


RationaleNovel Coronavirus-19(CoV-19) emerged in late 2019, leading to a global pandemic with over 1.5 million deaths worldwide and over 300,000 in the United States as of December 2020. Early data from China and the United States showed an increase risk in mortality in those individuals with comorbidities including chronic lung disease. Given the increase prevalence of chronic obstructive pulmonary disease (COPD) worldwide there was concern of increase mortality in this vulnerable population. We describe the Northwestern Medicine (NM) Hospital system experience with individuals with COPD. MethodsPatient data was obtained via the Northwestern Medicine Enterprise Data Warehouse (NMEDW), which is obtained via ten hospitals in the greater Chicagoland area that supply daily data to the NMEDW. Individuals who had a hospital encounter were identified with an ICD-10 coding for CoV-19 via the NM system between March 1, 2020 and July 16, 2020. Individuals would also be identified to have COPD via ICD-9 and ICD-10 coding. A simple chi-square analysis was done between characteristics using RStudio. ResultsA total of 5,585 individuals, with a CoV-19 diagnosis, were identified, of which 4,723 had a hospital encounter. Of those, a total of 296 patients were identified to have a COPD diagnosis. Of 4,427 without COPD, 53.1% were female, 17.9% Black, 38.2% Hispanic, 5.3% were current smokers, 47.3% required hospitalization, 13.9% required ICU admission, 8.1% required mechanical ventilation, and had a mortality rate of 3.8%. Of 296 patients with a COPD, 52.0% were female, 23.6% were black, 9.1% were Hispanic, 11.8% were current smokers, 84.1% required hospitalization, 31.8% required ICU admission, 19.6% required mechanical ventilation, and had a mortality rate of 14.2%. Table 1 below shows full characteristics of patients with CoV-19 diagnosis. ConclusionsInitial data of disease severity due to CoV-19 brought concerns about patients with COPD diagnosis and their increased risk of morbidity and mortality. We showcase NM system experience with individuals with COPD, that highlight higher rates of hospitalization, ICU stay, mechanical ventilation, investigational use of medication, and mortality. Given the discrepancy in age between groups, we acknowledge that it likely is a potential confounding variable for our outcomes. Further research into the severity of COPD and the outcomes of individuals with CoV-19 is required. .