A Metabolic Handbook for the COVID-19 Pandemic

Overview

Journal Nat Metab

Publisher Springer Nature

Specialty Endocrinology

Date 2020 Jul 23

PMID 32694793

Citations 151

Authors

Janelle S Ayres

Affiliations

Soon will be listed here.

Abstract

For infectious-disease outbreaks, clinical solutions typically focus on efficient pathogen destruction. However, the COVID-19 pandemic provides a reminder that infectious diseases are complex, multisystem conditions, and a holistic understanding will be necessary to maximize survival. For COVID-19 and all other infectious diseases, metabolic processes are intimately connected to the mechanisms of disease pathogenesis and the resulting pathology and pathophysiology, as well as the host defence response to the infection. Here, I examine the relationship between metabolism and COVID-19. I discuss why preexisting metabolic abnormalities, such as type 2 diabetes and hypertension, may be important risk factors for severe and critical cases of infection, highlighting parallels between the pathophysiology of these metabolic abnormalities and the disease course of COVID-19. I also discuss how metabolism at the cellular, tissue and organ levels might be harnessed to promote defence against the infection, with a focus on disease-tolerance mechanisms, and speculate on the long-term metabolic consequences for survivors of COVID-19.

Citing Articles

Analysis of differential expression of matrix metalloproteinases and defensins in the nasopharyngeal milieu of mild and severe COVID-19 cases.

Imtiaz K, Farooqui N, Ahmed K, Zhamalbekova A, Anwar M, Nasir A PLoS One. 2025; 20(2):e0304311.

PMID: 39965032 PMC: 11835293. DOI: 10.1371/journal.pone.0304311.

Fluoxetine promotes IL-10-dependent metabolic defenses to protect from sepsis-induced lethality.

Gallant R, Sanchez K, Joulia E, Snyder J, Metallo C, Ayres J Sci Adv. 2025; 11(7):eadu4034.

PMID: 39951524 PMC: 11827869. DOI: 10.1126/sciadv.adu4034.

Starve a cold or feed a fever? Identifying cellular metabolic changes following infection and exposure to SARS-CoV-2.

Loveday E, Welhaven H, Erdogan A, Hain K, Domanico L, Chang C PLoS One. 2025; 20(2):e0305065.

PMID: 39937842 PMC: 11819565. DOI: 10.1371/journal.pone.0305065.

Recent advances in nutritional metabolism studies on SARS-CoV-2 infection.

Jiang Y, Xu L, Zheng X, Shi H Infect Med (Beijing). 2025; 4(1):100162.

PMID: 39936106 PMC: 11810712. DOI: 10.1016/j.imj.2025.100162.

Perspectives on Microbiome Therapeutics in Infectious Diseases: A Comprehensive Approach Beyond Immunology and Microbiology.

Seo H, Kim S, Beck S, Song H Cells. 2024; 13(23).

PMID: 39682751 PMC: 11640688. DOI: 10.3390/cells13232003.

References

Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J . Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020; 323(11):1061-1069. PMC: 7042881. DOI: 10.1001/jama.2020.1585. View

Kappeler P, Cremer S, Nunn C . Sociality and health: impacts of sociality on disease susceptibility and transmission in animal and human societies. Philos Trans R Soc Lond B Biol Sci. 2015; 370(1669). PMC: 4410382. DOI: 10.1098/rstb.2014.0116. View

Mayer K, Stockl J, Zlabinger G, Gualdoni G . Hijacking the Supplies: Metabolism as a Novel Facet of Virus-Host Interaction. Front Immunol. 2019; 10:1533. PMC: 6617997. DOI: 10.3389/fimmu.2019.01533. View

Lin Y, Lin S, Huang T, Yang S, Lai T, Chen L . New-Onset Diabetes After Acute Kidney Injury Requiring Dialysis. Diabetes Care. 2018; 41(10):2105-2110. DOI: 10.2337/dc17-2409. View

Ardehali H, Sabbah H, Burke M, Sarma S, Liu P, Cleland J . Targeting myocardial substrate metabolism in heart failure: potential for new therapies. Eur J Heart Fail. 2012; 14(2):120-9. PMC: 3260022. DOI: 10.1093/eurjhf/hfr173. View

Sasannejad C, Wesley Ely E, Lahiri S . Long-term cognitive impairment after acute respiratory distress syndrome: a review of clinical impact and pathophysiological mechanisms. Crit Care. 2019; 23(1):352. PMC: 6852966. DOI: 10.1186/s13054-019-2626-z. View

Rao M, Dodoo E, Zumla A, Maeurer M . Immunometabolism and Pulmonary Infections: Implications for Protective Immune Responses and Host-Directed Therapies. Front Microbiol. 2019; 10:962. PMC: 6514247. DOI: 10.3389/fmicb.2019.00962. View

Batlle D, Soler M, Ye M . ACE2 and diabetes: ACE of ACEs?. Diabetes. 2010; 59(12):2994-6. PMC: 2992757. DOI: 10.2337/db10-1205. View

Akhmerov A, Marban E . COVID-19 and the Heart. Circ Res. 2020; 126(10):1443-1455. DOI: 10.1161/CIRCRESAHA.120.317055. View

10.

Booth C, Matukas L, Tomlinson G, Rachlis A, Rose D, Dwosh H . Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area. JAMA. 2003; 289(21):2801-9. DOI: 10.1001/jama.289.21.JOC30885. View

11.

Smallwood H, Duan S, Morfouace M, Rezinciuc S, Shulkin B, Shelat A . Targeting Metabolic Reprogramming by Influenza Infection for Therapeutic Intervention. Cell Rep. 2017; 19(8):1640-1653. PMC: 5599215. DOI: 10.1016/j.celrep.2017.04.039. View

12.

Yang J, Lin S, Ji X, Guo L . Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes. Acta Diabetol. 2009; 47(3):193-9. PMC: 7088164. DOI: 10.1007/s00592-009-0109-4. View

13.

Sanchez K, Chen G, Schieber A, Redford S, Shokhirev M, Leblanc M . Cooperative Metabolic Adaptations in the Host Can Favor Asymptomatic Infection and Select for Attenuated Virulence in an Enteric Pathogen. Cell. 2018; 175(1):146-158.e15. PMC: 6447043. DOI: 10.1016/j.cell.2018.07.016. View

14.

Haley M, White C, Roberts D, OToole K, Cunningham C, Rivers-Auty J . Stroke Induces Prolonged Changes in Lipid Metabolism, the Liver and Body Composition in Mice. Transl Stroke Res. 2019; 11(4):837-850. PMC: 7340675. DOI: 10.1007/s12975-019-00763-2. View

15.

Channappanavar R, Fehr A, Vijay R, Mack M, Zhao J, Meyerholz D . Dysregulated Type I Interferon and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice. Cell Host Microbe. 2016; 19(2):181-93. PMC: 4752723. DOI: 10.1016/j.chom.2016.01.007. View

16.

Tziomalos K, Athyros V . Diabetic Nephropathy: New Risk Factors and Improvements in Diagnosis. Rev Diabet Stud. 2015; 12(1-2):110-8. PMC: 5397986. DOI: 10.1900/RDS.2015.12.110. View

17.

Chavez P, Stanley W, McElfresh T, Huang H, Sterk J, Chandler M . Effect of hyperglycemia and fatty acid oxidation inhibition during aerobic conditions and demand-induced ischemia. Am J Physiol Heart Circ Physiol. 2003; 284(5):H1521-7. DOI: 10.1152/ajpheart.00974.2002. View

18.

Wang Q, Fang P, He R, Li M, Yu H, Zhou L . -GlcNAc transferase promotes influenza A virus-induced cytokine storm by targeting interferon regulatory factor-5. Sci Adv. 2020; 6(16):eaaz7086. PMC: 7159909. DOI: 10.1126/sciadv.aaz7086. View

19.

Ayres J, Schneider D . Tolerance of infections. Annu Rev Immunol. 2012; 30:271-94. DOI: 10.1146/annurev-immunol-020711-075030. View

20.

Fogo A . PPARγ and chronic kidney disease. Pediatr Nephrol. 2010; 26(3):347-51. DOI: 10.1007/s00467-010-1602-2. View