Integrated cytokine and metabolite analysis reveals immunometabolic reprogramming in COVID-19 patients with therapeutic implications

Nan Xiao, Meng Nie, Huanhuan Pang, Bohong Wang, Jieli Hu, Xiangjun Meng, Ke Li, Xiaorong Ran, Quanxin Long, Haijun Deng, Na Chen, Shao Li, Ni Tang (), Ailong Huang () and Zeping Hu ()
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Nan Xiao: Tsinghua University
Meng Nie: Tsinghua University
Huanhuan Pang: Tsinghua University
Bohong Wang: Tsinghua University
Jieli Hu: Chongqing Medical University
Xiangjun Meng: Tsinghua University
Ke Li: NHC Key Laboratory of Biotechnology of Antibiotics, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College
Xiaorong Ran: Agilent Technologies (China), Chaoyang District
Quanxin Long: Chongqing Medical University
Haijun Deng: Chongqing Medical University
Na Chen: Tsinghua University
Shao Li: Tsinghua University
Ni Tang: Chongqing Medical University
Ailong Huang: Chongqing Medical University
Zeping Hu: Tsinghua University

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: Abstract 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. Metabolism can modulate the immune responses against infectious diseases, yet our understanding remains limited on how host metabolism correlates with inflammatory responses and affects cytokine release in COVID-19 patients. Here we perform both metabolomics and cytokine/chemokine profiling on serum samples from healthy controls, mild and severe COVID-19 patients, and delineate their global metabolic and immune response landscape. Correlation analyses show tight associations between metabolites and proinflammatory cytokines/chemokines, such as IL-6, M-CSF, IL-1α, IL-1β, and imply a potential regulatory crosstalk between arginine, tryptophan, purine metabolism and hyperinflammation. Importantly, we also demonstrate that targeting metabolism markedly modulates the proinflammatory cytokines release by peripheral blood mononuclear cells isolated from SARS-CoV-2-infected rhesus macaques ex vivo, hinting that exploiting metabolic alterations may be a potential strategy for treating fatal CRS in COVID-19.

Date: 2021
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DOI: 10.1038/s41467-021-21907-9

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