Host metabolite-cytokine correlation landscape in SARS-CoV-2 infection

Abstract

The systemic cytokine release syndrome (CRS) is a major cause of the multi-organ injury and fatal outcome induced by SARS-CoV-2 infection in severe COVID-19 patients. It has been well-known that metabolism plays a role in modulating the immune responses in infectious diseases. Yet, how the host metabolism correlates with CRS in COVID-19 patients and how the perturbed metabolites affect the cytokine release remains unclear. Here, we performed both metabolomics and cytokine/chemokine profiling on serum samples from the same cohort of healthy controls, mild and severe COVID-19 patients and delineated the global metabolic and immune response landscape along disease progression. Intriguingly, the correlation analysis revealed the tight link between metabolites and proinflammatory cytokines and chemokines, such as IL-6, M-CSF, IL-1α, IL-1β, implying the potential regulatory role of arginine metabolism, tryptophan metabolism, and purine metabolism in hyperinflammation. Importantly, we demonstrated that targeting metabolism markedly modulated the proinflammatory cytokines release by PBMCs isolated from SARS-CoV-2-infected rhesus macaques ex vivo. Beyond providing a comprehensive resource of metabolism and immunology data of SARS-CoV-2 infection, our study showed that metabolic alterations can be potentially exploited to develop novel strategy for the treatment of fatal CRS in COVID-19.

Serum metabolomic abnormalities in survivors of non-severe COVID-19

“…Metabolic reprogramming is initiated by virus for their replication and survival and also modulated by the immune response after SARS-CoV-2 infection (Shen and Wang, 2021;Xiao et al 2021). Several metabolic pathways, mainly including amino acids, energy, lipids and immune-related metabolism, were reprogrammed in hospitalized COVID-19 patients (Su et al, 2020;Shen et al, 2020;Costanzo et al, 2022b).…”