Comparative Metabolomic Analysis Reveals Shared and Unique Features of Covid-19 Cytokine Storm and Surgical Sepsis

Abstract

Background and aims The clinical manifestations of the cytokine storm (CS) associated with COVID-19 resemble the acute phase of sepsis. Metabolomics may contribute to understanding the specific pathobiology of these two syndromes. The aim of this study was to compare serum metabolomic profiles in patients with CS associated with COVID-19 and in septic patients after surgery.

Materials and methods In retrospective cross-sectional study serum samples from COVID-19-CS patients, with comorbidity (n=43) and without comorbidity (n=40) as well as serum samples from patients with surgical sepsis (n=41) were investigated. Serum samples from healthy volunteers (n=110) were used as a control. A targeted metabolomic analysis was carried out in all samples using LC-MS/MS method. The R programming language was used for statistical data processing.

Results Analysis revealed that similar alterations in serum metabolome of patients with COVID-19 and in septic patients were associated with amino acid metabolism, nitrogen metabolism, inflammatory status, methionine cycle and glycolysis. The most significant difference was identified for the serum levels of metabolites of kynurenine synthesis, tricarboxylic acid cycle, as well as for gamma-aminobutyric acid and niacinamide. The metabolic pathway of cysteine and methionine metabolism was disturbed significantly in COVID-19 and septic patients.

Conclusion The study revealed common and different metabolic patterns in the serum of patients with CS associated with COVID-19 and in the serum of septic patients.

Note:
Funding Information: Supported by Saint Petersburg State University, project ID: 95412780.

Declaration of Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Ethics Approval Statement: The study was conducted within the framework of the research project "Biobanking and biomedical research of human tissue and fluid samples" and was approved by the Expert Council on Ethics of the St. Petersburg State Healthcare Establishment "City Hospital No. 40" (session No. 119, February 9, 2017). Informed consent for sample collection and placing samples in a biobank for subsequent use for scientific purposes and for the results' publication was obtained from all patients. The study was conducted following the World Medical Association’s Code of Ethics (Declaration of Helsinki) for experiments involving humans.

Keywords: COVID-19, Cytokine Storm, sepsis, targeted metabolomic analysis, LC-MS/MS, metabolic pathways