# Identification of metabolic signatures of immune response following mRNA and inactivated vaccines against COVID-19: a systematic review

## TL;DR

This review identifies metabolic changes after mRNA and inactivated COVID-19 vaccines, highlighting potential biomarkers for immune response.

## Contribution

The study systematically reviews metabolomic changes post-COVID-19 vaccination, identifying novel metabolic signatures linked to immune response.

## Key findings

- Vaccination alters amino acid pathways like glutamine, phenylalanine, and tryptophan.
- Early kynurenine pathway activation predicts stronger antibody responses.
- Inactivated vaccines induce a Warburg-like metabolic switch with increased glycolysis.

## Abstract

Metabolomic profiling offers insights into immune responses, yet a synthesis of systemic metabolic changes after COVID-19 vaccination is lacking. This review aims to characterize vaccination-induced metabolomic alterations and identify correlative biomarkers of responsiveness.

Following PRISMA 2020 guidelines (PROSPERO 1181037), four databases (PubMed, Embase, Scopus, Web of Science) were searched for studies using LC-MS, GC-MS, or NMR to analyse venous blood after COVID-19 vaccination. Inclusion criteria focused on original human studies. Risk of bias was assessed using ROBINS-I and RoB 2.

Ten studies (n > 1,200) evaluating mRNA and inactivated vaccines were included. Vaccination consistently altered amino acid pathways, specifically glutamine, phenylalanine, and tryptophan. Early activation of the kynurenine pathway (1–2 days post-dose) emerged as a predictor of stronger antibody responses. Inactivated vaccines triggered a “Warburg-like” metabolic switch, characterized by increased glycolysis and reduced TCA intermediates. Lipidomic changes were prominent; high baseline ceramides predicted low response, while sphingomyelins and short-chain fatty acids associated with positive immunity. Most studies showed a moderate risk of bias due to post-hoc grouping and confounding factors.

COVID-19 vaccination induces reproducible changes in amino acid, energy, and lipid metabolism. Kynurenine activity, baseline amino acids, and sphingolipid signatures are potential predictors of vaccine efficacy, supporting personalized immunization strategies.