SARS-CoV-2 directly triggers hyperglycemia by infecting hepatocytes

Modern societies are facing a growing burden of non-communicable diseases (NCDs), which include conditions such as cardiovascular diseases, cancers, chronic respiratory diseases, and diabetes.

At the same time, the twenty-first century has witnessed the emergence of new infectious diseases and the re-emergence of existing ones.

The COVID-19 pandemic has further highlighted the complex relationship between infectious and non-communicable diseases, shedding light on the impact of viral infections on existing health conditions and the potential links between viral infections and the onset of NCDs.

One of the key observations during the COVID-19 pandemic is the influence of host risk factors on the course of the disease. Lifestyle factors, obesity/overweight, and comorbidities have been identified as risk factors for severe COVID-19 outcomes. There is also evidence of genetic predisposition and underlying immune-related conditions playing a role in the susceptibility to and severity of COVID-19.

Additionally, demographic differences among affected individuals have been observed. However, the molecular mechanisms and causal links between viral infections and NCDs are still not fully understood.

A recent study by Barreto and colleagues provided valuable insights into the connection between SARS-CoV-2, the virus causing COVID-19, and the development of hyperglycemia. The researchers found that SARS-CoV-2 directly triggers hyperglycemia by infecting hepatocytes, liver cells responsible for glucose production.

They used clinical and laboratory data, as well as postmortem liver biopsies, to demonstrate the presence of the virus and its receptors in hepatocytes. Furthermore, they showed that infected hepatocytes increase glucose production through a process called gluconeogenesis, which involves the activation of specific enzymes.

The evidence of SARS-CoV-2 infecting hepatocytes raises the question of whether the virus should be added to the list of hepatotropic viruses, which are known to target the liver. While the lungs and respiratory tract are the primary sites of SARS-CoV-2 replication, there is robust evidence indicating its hepatic tropism.

Hepatocytes express the receptors ACE-2 and TMPRS22, which the virus uses to enter human cells. Autopsy findings have also revealed efficient replication of SARS-CoV-2 in the liver. However, the exact mechanisms of viral entry and the involvement of other liver cell types, such as cholangiocytes, remain to be fully elucidated.

The manipulation of hepatic metabolism by SARS-CoV-2 has implications for patients experiencing long COVID-19, the post-acute sequelae of the disease. There is evidence of patients developing type 2 diabetes (T2D) months after acute infection with SARS-CoV-2. The incidence of diabetes after COVID-19 has been found to be higher compared to the control group. The reasons for this development of T2D are not entirely clear, but potential explanations include viral persistence and chronic infection, as well as long-lasting epigenetic alterations of metabolism induced by SARS-CoV-2.

Understanding the molecular mechanisms underlying the glucometabolic control by SARS-CoV-2 in the liver is crucial for identifying potential therapeutic targets and developing interventions to mitigate the long-term effects of COVID-19. Further research is needed to explore the various molecular signatures and mechanisms involved in the modulation of glucose metabolism by SARS-CoV-2, including the potential role of viral microRNAs, metabolic enzyme alterations, and epigenetic modifications.

The interplay between infectious and non-communicable diseases, exemplified by the COVID-19 pandemic, presents a complex and multifaceted challenge for modern societies. The connection between SARS-CoV-2 and the liver highlights the need for a deeper understanding of the molecular mechanisms underlying the relationship between viral infections and viral infections and non-communicable diseases, particularly those related to metabolic health.

The direct impact of SARS-CoV-2 on hepatic metabolism and the development of hyperglycemia underscores the importance of studying the long-term consequences of COVID-19 and its potential role in the onset or exacerbation of conditions such as diabetes.

Moreover, the relationship between viral infections and non-communicable diseases extends beyond SARS-CoV-2. For example, chronic viral infections such as hepatitis B and C viruses have long been associated with liver diseases, including liver cirrhosis and hepatocellular carcinoma. These infections can lead to chronic inflammation, fibrosis, and liver dysfunction, which can contribute to the development of liver-related non-communicable diseases.

In the context of COVID-19, it is crucial to consider the broader implications of the virus on population health and healthcare systems. The pandemic has disrupted healthcare services, including routine screenings, preventive care, and management of chronic conditions. This disruption can have far-reaching consequences, potentially leading to delayed diagnoses, inadequate disease management, and increased disease burden in the long run.

Addressing the interconnectedness of infectious and non-communicable diseases requires a comprehensive and integrated approach. Public health measures should aim to control the spread of infectious diseases while also promoting healthy lifestyles, early detection of non-communicable diseases, and effective management of comorbidities.

This includes initiatives such as vaccination campaigns, health education programs, accessible healthcare services, and research efforts to deepen our understanding of the complex interactions between viruses and non-communicable diseases.

Furthermore, collaboration between various disciplines, including virology, immunology, epidemiology, and metabolic research, is essential to unravel the underlying mechanisms linking viral infections and non-communicable diseases. This interdisciplinary approach can inform the development of targeted interventions, therapeutics, and public health strategies to mitigate the long-term consequences of both infectious and non-communicable diseases.

In conclusion, the COVID-19 pandemic has shed light on the intricate relationship between viral infections and non-communicable diseases. The direct impact of SARS-CoV-2 on hepatic metabolism and the development of hyperglycemia highlights the need for further research to understand the molecular mechanisms involved.

By elucidating these mechanisms and considering the broader implications of infectious diseases on non-communicable diseases, we can work towards a more comprehensive and effective approach to global health.

reference link: https://www.cell.com/trends/molecular-medicine/fulltext/S1471-4914(23)00115-6