COVIDomics: The Proteomic and Metabolomic Signatures of COVID-19

Abstract

Omics-based technologies have been largely adopted during this unprecedented global COVID-19 pandemic, allowing the scientific community to perform research on a large scale to understand the pathobiology of the SARS-CoV-2 infection and its replication into human cells. The application of omics techniques has been addressed to every level of application, from the detection of mutations, methods of diagnosis or monitoring, drug target discovery, and vaccine generation, to the basic definition of the pathophysiological processes and the biochemical mechanisms behind the infection and spread of SARS-CoV-2. Thus, the term COVIDomics wants to include those efforts provided by omics-scale investigations with application to the current COVID-19 research. This review summarizes the diverse pieces of knowledge acquired with the application of COVIDomics techniques, with the main focus on proteomics and metabolomics studies, in order to capture a common signature in terms of proteins, metabolites, and pathways dysregulated in COVID-19 disease. Exploring the multiomics perspective and the concurrent data integration may provide new suitable therapeutic solutions to combat the COVID-19 pandemic.

COVID-19 and One-Carbon Metabolism

“…A summary of over twenty proteomic studies on plasma and serum of COVID-19 patients revealed three deregulated KEGG pathways: complement and coagulation cascades, cytokine-cytokine receptor interaction and cholesterol metabolism [5]. Elevations of inflammation biomarkers such as IL (interleukin)-6, IL-2, IL-7, TNF (tumor necrosis factor), MCP (monocyte chemoattractant protein)-1, MIP (macrophage inflammatory protein)-1, G-CSF (granulocyte-colony stimulating factor), CRP (C-reactive protein), procalcitonin and ferritin are associated with increased mortality [4] and higher disease severity [6].…”

“…Patients with comorbidities (hypertension, cardiovascular disease, renal insufficiency, autoimmune disease) associated with severe COVID-19 have increased expression of ACE2 is their lungs [51]. mACE2 also serves as the entry point into cells for some coronaviruses, including HCoV-NL63, SARS-CoV, and SARS-CoV-2 [5]. It has been suggested that subjects with comorbidities may have higher chances of developing severe COVID-19, since ACE2 facilitates SARS-CoV-2 entry into the lung cells [51].…”

Sex differences in the human metabolome

“…However, many published studies did not stratify the data by sex and did not analyze the data by sex. Even from the current COVID-19 research are perceivable a scarce enrollment of women and a poor stratification of the subjects, and any further analysis based on the sex [ 32 ], providing collective results and conclusions valid for both the sexes [ 33 , 34 ]. Furthermore, the sex differences found in the metabolome vary consistently across different age ranges, from infants to young adults, to the elderly [ 24 , 35 – 38 ], underlining the importance of age in determining the sex differences.…”

Proteomic and Metabolomic Signatures Associated With the Immune Response in Healthy Individuals Immunized With an Inactivated SARS-CoV-2 Vaccine

“…Beside immunogenicity, inflammation evaluation is another important parameter for vaccine evaluation. Recently, a growing body of clinical data suggests that proteomic and metabolic dysregulation are associated with COVID-19 pathogenesis ( 18 , 19 ). For example, acute phase proteins (APPs) including serum amyloid A-1 (SAA1), SAA2, SAA4 and C-reactive protein (CRP) were increased in severe COVID-19 patients, indicating activation of inflammation and the complement system ( 18 ).…”