Plasma metabolomic characterization of SARS-CoV-2 Omicron infection

Abstract

Omicron variants of SARS-CoV-2 have spread rapidly worldwide; however, most infected patients have mild or no symptoms. This study aimed to understand the host response to Omicron infections by performing metabolomic profiling of plasma. We observed that Omicron infections triggered an inflammatory response and innate immune, and adaptive immunity was suppressed, including reduced T-cell response and immunoglobulin antibody production. Similar to the original SARS-CoV-2 strain circulating in 2019, the host developed an anti-inflammatory response and accelerated energy metabolism in response to Omicron infection. However, differential regulation of macrophage polarization and reduced neutrophil function has been observed in Omicron infections. Interferon-induced antiviral immunity was not as strong in Omicron infections as in the original SARS-CoV-2 infections. The host response to Omicron infections increased antioxidant capacity and liver detoxification more than in the original strain. Hence, these findings suggest that Omicron infections cause weaker inflammatory alterations and immune responses than the original SARS-CoV-2 strain.

Fig. 1. Overview of the study design.

A Schematic summary of study design and participants. B PCA diagram of metabolomic data from plasma samples. Each dot represents a plasma sample, and different colors mark different groups. The green, orange, and blue data points were the healthy control group, the infected group, and the recovered group, respectively. C–E Displays volcano plots comparing three pairs of groups. Each point in the volcano plots represents a metabolite. The metabolites with FDR < 0.05 were considered to be significant differences. Red represents the upregulated metabolites; green represents the downregulated metabolites. The size of the dot represents the VIP value.

Fig. 2. Metabolomic profiling of plasma samples obtained from patients with Omicron and healthy participants.

A Heatmap visualization of significantly different altered metabolites (DEMs) in infected, recovered patients and healthy control participants. Metabolites in the heatmap showed a fold-change >1.5 and FDR < 0.05. The color bar represents the relative intensity of identified metabolites from −6 to 6. B Bubble plots show the top 10 KEGG enrichment pathways. The ratio is the number of differential metabolites in the related metabolic pathway to the number of total metabolites identified in the pathway. The color of the dots represents −log₁₀ (p value). The size of the dots represents the number of differential metabolites in the corresponding pathway.

Fig. 3. Differential metabolites between patients with Omicron patients and healthy participants.

For the healthy control group, n = 33; for the infected group, n = 19; and for the recovered group, n = 31. ns: nonsignificant. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.

Fig. 4. Expression profiles were analyzed according to metabolic abundance between patients with COVID-19 and healthy participants.

A The result of cluster analysis in processing conditions (Healthy-Infected-Recovered) by the Mfuzz package, M1–M3. The color bar represents the Z score change from −1 to 1. B–D Heatmap visualization of metabolites in M1–M3 under the processing conditions (healthy, infected, recovered). The color bar represents the relative intensity of identified metabolites from −4 to 4.

Fig. 5. Comparison of plasma metabolomics of Omicron infection with the original strain.

A Flowchart for screening published articles of plasma metabolomic analysis in patients with COVID-19. B The number of differential metabolites and KEGG enrichment pathway in patients with COVID-19 infected with Omicron and the original strains. C The Venn diagram compares enrichment pathways between the Omicron and the original strains. D Shared differential metabolites in patients infected with the Omicron and the original strains, respectively. The red metabolites present the opposite change from Omicron patients to the original strain.