Large-Scale Multi-omic Analysis of COVID-19 Severity

Abstract

We performed RNA-seq and high-resolution mass spectrometry on 128 blood samples from COVID-19-positive and COVID-19-negative patients with diverse disease severities and outcomes. Quantified transcripts, proteins, metabolites, and lipids were 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 of which were 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 machine learning approach for prediction of COVID-19 severity.

Genetic architecture of host proteins involved in SARS-CoV-2 infection

“…Individuals with genetic susceptibility to a higher WHR had higher abundances of four putative viral interaction partners (LMAN2, ETFA, TBCA, and SELENOS), and lower levels of albumin, GSN, and ITIH3. Lower plasma abundances of GSN have been repeatedly associated with severity of COVID-19 7,22 . The association with plasma abundances of LMAN2 (or VIP36) was shared with the eGFR-GRS but in opposing direction (inversely).…”

COVID-19 biomarkers for severity mapped to polycystic ovary syndrome

“…Limitations of the study include utilizing a different method of proteomic analysis compared to others that may not be directly comparable [1]. In conclusion, 21 of 60 protein biomarkers reported in respiratory patients with COVID-19 were found to differ between women with and without PCOS, showing the necessity for validation of such biomarkers, and suggesting that more severe COVID-19 disease may occur in PCOS.…”

“…To the Editor, Large scale multi-omics analysis has identified significant differences in the biomarkers between COVID-19 disease and control subjects [1]. These protein panels target biological processes involved in vessel damage, platelet degranulation, the coagulation cascade and the acute phase response [1], with greater protein changes dependent on the COVID-19 severity.…”

SARS-CoV-2 RNAemia and proteomic biomarker trajectory inform prognostication in COVID-19 patients admitted to intensive care

“…Further, we hypothesized that the acute and profound alterations in the innate and adaptive immune system in COVID-19 patients 3,[11][12][13] , especially in RNAemic patients [14][15][16][17][18] , will be accompanied by marked changes in the circulating proteome and interactome and that the proteome in COVID-19 patients will highlight mechanistically relevant signatures and trajectories, when compared to non-COVID-19 sepsis and healthy controls. Thus far, proteomics studies have focused on the determination of protein biomarkers of COVID-19 severity [19][20][21][22] , but have not assessed the longitudinal relationship between proteomic changes, RNAemia and 28-day mortality.…”