ABSTRACT
We performed RNA-Seq and high-resolution mass spectrometry on 128 blood samples from COVID-19 positive and negative patients with diverse disease severities. Over 17,000 transcripts, proteins, metabolites, and lipids were quantified and associated with clinical outcomes in a curated relational database, uniquely enabling systems analysis and cross-ome correlations to molecules and patient prognoses. We mapped 219 molecular features with high significance to COVID-19 status and severity, many involved in complement activation, dysregulated lipid transport, and neutrophil activation. We identified sets of covarying molecules, e.g., protein gelsolin and metabolite citrate or plasmalogens and apolipoproteins, offering pathophysiological insights and therapeutic suggestions. The observed dysregulation of platelet function, blood coagulation, acute phase response, and endotheliopathy further illuminated the unique COVID-19 phenotype. We present a web-based tool (covid-omics.app) enabling interactive exploration of our compendium and illustrate its utility through a comparative analysis with published data and a machine learning approach for prediction of COVID-19 severity.
ABSTRACT
The COVID19 pandemic is likely to cause more than a million of deaths worldwide, primarily due to complications from COVID19-associated acute respiratory distress syndrome (ARDS). Controversy surrounds the circulating cytokine/chemokine profile of COVID19-associated ARDS, with some groups suggesting that it is similar to non-COVID19 ARDS patients and others observing substantial differences. Moreover, while a hyperinflammatory phenotype associates with higher mortality in non-COVID19 ARDS, there is little information on the inflammatory landscapes association with mortality in COVID19 ARDS patients. Even though the circulating leukocytes transcriptomic signature has been associated with distinct phenotypes and outcomes in critical illness including ARDS, it is unclear whether the mortality-associated inflammatory mediators from COVID19 patients are transcriptionally regulated in the leukocyte compartment. Here, we conducted a prospective cohort study of 41 mechanically ventilated patients with COVID19 infection using highly calibrated methods to define the levels of plasma cytokines/chemokines and their gene expressions in circulating leukocytes. Plasma IL1RA and IL8 were found positively associated with mortality while RANTES and EGF negatively associated with that outcome. However, the leukocyte gene expression of these proteins had no statistically significant correlation with mortality. These data suggest a unique inflammatory signature associated with severe COVID19.
ABSTRACT
The 2015 annual meeting of the Americas Association of Sarcoidosis and Other Granulomatous Disorders (AASOG) was held on September 25th and 26th at the University of Colorado Anschutz Medical Campus in Aurora, CO, U.S.A. The meeting was hosted by National Jewish Health and the theme of the meeting was "Reducing Disparities in Sarcoidosis through Personalized Care and Increased Detection". The meeting was endorsed by the American Thoracic Society (ATS) and the Foundation for Sarcoidosis Research (FSR), and was conducted through support provided by the National Institutes of Health (NIH), particularly the National Heart Lung and Blood Institute (NHLBI), and an unrestricted educational grant from Mallinckrodt, Inc. The meeting participants were predominantly from North America, and included preeminent experts and emerging clinical scientists engaged in sarcoidosis research. The AASOG meeting was held in parallel with a sarcoidosis patient conference that was organized and funded by the Foundation of Sarcoidosis Research (FSR). The AASOG talks covered various state-of-the-arts topics related to sarcoidosis research and care; most notable were talks focusing on preliminary and emerging data from the Genomic Research in Alpha-1 antitrypsin Deficiency and Sarcoidosis (GRADS) study, recent novel immunological and genomic discoveries that further our understanding of sarcoidosis disease pathogenesis, results from clinical trials in sarcoidosis and proposals of novel therapeutic targets for the treatment of sarcoidosis, the introduction of the FSR sponsored clinical studies network, insights from other granulomatous diseases, and a focus on extra-pulmonary sarcoidosis, particularly cardiac disease, small fiber neuropathy, and fatigue. A session dedicated to scientific abstracts from predominantly junior investigators and five oral abstract presentations brought the conference to a conclusion. A brief overview and selected excerpts of the 2015 AASOG meeting proceedings are provided herein. (Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 264-268).
