PRJNA660067: Large-scale Multi-omic Analysis of COVID-19 Severity
Summary: Using RNA-seq and high-resolution mass spectrometry we performed a comprehensive systems analysis on 128 plasma and leukocyte samples from hospitalized patients with or without COVID-19 (n=102 and 26 respectively) and with differing degrees of disease severity. We generated abundance measurements for over 17,000 transcripts, proteins, metabolites, and lipids and compiled them with clinical data into a curated relational database. This resource offers the unique opportunity to perform systems analysis and cross-ome correlations to both molecules and patient outcomes. In total 219 molecular features were mapped with high significance to COVID-19 status and severity, including those involved in processes such as complement system activation, dysregulated lipid transport, and B cell activation. In one example, we detected a trio of covarying molecules 鈥?citrate, plasmenyl-phosphatidylcholines, and gelsolin (GSN) 鈥?that offer both pathophysiological insight and potential novel therapeutic targets. Further, our data revealed in some cases, and supported in others, that several biological processes were dysregulated in COVID-19 patients including vessel damage, platelet activation and degranulation, blood coagulation, and acute phase response. For example, we observed that the coagulation-related protein, cellular fibronectin (cFN), was highly increased within COVID-19 patients and provide new evidence that the upregulated proteoform stems from endothelial cells, consistent with endothelial injury as a major activator of the coagulation cascade. The abundance of prothrombin, which is cleaved to form thrombin during clotting, was significantly reduced and correlated with severity and might help to explain the hyper coagulative environment of SARS-CoV-2 infection. From transcriptomic analysis of leukocytes, we concluded that COVID-19 patients with acute respiratory distress syndrome (ARDS) demonstrated a phenotype that overlapped with, but was distinct from, that found in patients with non-COVID-19-ARDS. To aid in the global efforts toward elucidation of disease pathophysiology and therapeutic development, we created a web-based tool with interactive visualizations allowing for easy navigation of this systems-level compendium of biomolecule abundance in relation to COVID-19 status and severity. Finally, we leveraged these multi-omic data to predict COVID-19 patient outcomes with machine learning, which highlighted the predictive power of these expansive molecular measurements beyond the standardized clinical estimate of 10-year survival Charlson score.
Overall Design: 126 samples were analyzed in total with 100 COVID-19 patients and 26 non-COVID-19
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10mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 11mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 12mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 13mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 14mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 15mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 16mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 17mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 18mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 19mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 20mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 21mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 22mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 23mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 24mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 25mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 26mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 27mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 28mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 29mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 30mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 31mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 32mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 33mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 34mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 35mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 36mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 37mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 38mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 39mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 40mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 41mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 42mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 43mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 44mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 45mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 46mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 47mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 48mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 49mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 50mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 51mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 52mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 53mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 54mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 55mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 56mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 57mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 58mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 59mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 60mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 61mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 62mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 63mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 64mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 65mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 66mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 67mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 68mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 69mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 70mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 71mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 72mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 73mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 74mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 75mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 76mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 77mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 78mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 79mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 80mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 81mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 82mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 83mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 84mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 85mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 86mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 87mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 88mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 89mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 90mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 91mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 92mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 93mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 94mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 95mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 96mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 97mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 98mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 99mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 100mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 101mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 102mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 103mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 104mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 105mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 106mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 107mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 108mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 109mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 110mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 111mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 112mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 113mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 114mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 115mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 116mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 117mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 118mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 119mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 120mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 121mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 122mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 123mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 124mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 125mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 126mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 127mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 128mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 129mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 130mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 131mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 132mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 133mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 134mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System.; 135mL of whole blood collected from patients was filtered and RNA was isolated using LeukoLOCK Total RNA Isolation System. |
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Large-Scale Multi-omic Analysis of COVID-19 Severity.
Cell systems . 2020-10-08 [PMID:
33096026]
