Lessons learned by the SARS-CoV epidemic: Viral modulation of the host's glucose and lipid metabolism
The recently emerged COVID-19 pandemic has been met with a rapid response from the scientific community, both in generating and disseminating clinical data, and in preclinical data generation. Among the first studies to report clinical data on COVID-19 was a recent publication by Xu et al (1). The authors provide detailed clinical and laboratory data, contributing to a growing body of evidence (2) that will allow researchers to phenotype infection patterns and outcomes. Currently, there are more questions than answers regarding the COVID-19.
In this light, previous knowledge stemming from the 2002-2003 SARS-CoV epidemic should be utilized, on the premises of structural and syndromic similarities between SARS-CoV and SARS-CoV-2 (3),(4).
Meta-analyses on SARS cohorts have indicated that both a history of diabetes and hyperglycemia were independent factors of worse outcomes including more severe respiratory symptoms and death, regardless of medication (5). In another study, SARS-CoV was shown to cause diabetes by ACE2-dependent infection of pancreatic isle cells (6).
Aside from ACE2 dependent entry, lipid metabolism is an important target of single strand RNA viruses, critical for the formation of the viral envelope in subsequent lifecycles (7). Autophagy mediated triglyceride and lipid droplet catabolism is one such mechanism, as identified in DENV (8). Hijacking the host cell's lipid metabolism has been shown to be a critical step in HCoV-22E and MERS - coronavirus latency (9). In SARS-CoV patients, alterations in lipid metabolism have been detected as far as 12 years after the initial infection, and were found to be related to corticosteroid treatment (10).
By contrast, diabetes has arisen as recurring comorbidity in COVID-19 cohorts (11), whereas lipid profiles remain unreported. Currently, no study has reported on the lipid profiles of COVID-19 patients. Given the role of lipids such as cholesterol in SARS virion assembly, preclinical pharmacotherapy / drug repurposing concepts have been developed (12). In this light, it is equally important to phenotype (i) COVID-19 patients receiving both antidiabetic and hypolipidemic agents and related comorbidities, (ii) to determine the de novo development of hyperglycemia / diabetes (iii) the long term follow up of COVID-19 patients, with respect to the future development of metabolic comorbidities.
1. Xu XW, Wu XX, Jiang XG, et al. Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series. BMJ. 2020;368:m606.
2. Zhang X, Cai H, Hu J, et al. Epidemiological, clinical characteristics of cases of SARS-CoV-2 infection with abnormal imaging findings, International Journal of Infectious Diseases 2020; doi: https://doi.org/10.1016/j.ijid.2020.03.040
3. Ceccarelli M, Berretta M, Venanzi rullo E, Nunnari G, Cacopardo B. Differences and similarities between Severe Acute Respiratory Syndrome (SARS)-CoronaVirus (CoV) and SARS-CoV-2. Would a rose by another name smell as sweet?. Eur Rev Med Pharmacol Sci. 2020;24(5):2781-2783.
4. Xu J, Zhao S, Teng T, et al. Systematic Comparison of Two Animal-to-Human Transmitted Human Coronaviruses: SARS-CoV-2 and SARS-CoV. Viruses. 2020;12(2)
5. Yang JK, Feng Y, Yuan MY, et al. Plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with SARS. Diabet Med. 2006;23(6):623-8.
6. Yang JK, Lin SS, Ji XJ, Guo LM. Binding of SARS coronavirus to its receptor damages islets and causes acute diabetes. Acta Diabetol. 2010;47(3):193-9.
7. Zhang Z, He G, Filipowicz NA, et al. Host Lipids in Positive-Strand RNA Virus Genome Replication. Front Microbiol. 2019;10:286.
8. Heaton NS, Randall G. Dengue virus-induced autophagy regulates lipid metabolism. Cell Host Microbe. 2010;8(5):422-32.
9. Zhang J, Lan Y, Sanyal S. Modulation of Lipid Droplet Metabolism-A Potential Target for Therapeutic Intervention in Infections. Front Microbiol. 2017;8:2286.
10. Wu Q, Zhou L, Sun X, et al. Altered Lipid Metabolism in Recovered SARS Patients Twelve Years after Infection. Sci Rep. 2017;7(1):9110.
11. Yang J, Zheng Y, Gou X, et al. Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: a systematic review and meta-analysis. Int J Infect Dis. 2020; 10.1016/j.ijid.2020.03.017
12. Baglivo M, Baronio M, Natalini G, et al. Natural small molecules as inhibitors of coronavirus lipid-dependent attachment to host cells: a possible strategy for reducing SARS-COV-2 infectivity?. Acta Biomed. 2020;91(1):161-164.
Competing interests: No competing interests