New biomarker for severe COVID-19

Credit: Gerd Altmann/Public Domain/Pixabay
It has been shown that those with obesity and cardiovascular disease are more likely to develop COVID-19, a fatal, severe disease. Karolinska Institutet researchers have identified the metabolic processes used by SARS-CoV-2 to attack lung tissue. These results were published in Molecular & Cellular Proteomics. They could be used to treat COVID-19 and possibly other viruses such as the Crimean-Congo hemorhagic fever virus (Civilian-Congo) and HIV-1.

SARS-CoV-2 virus has caused a global pandemic known as the corona crisis. The majority of people who become ill with the disease experience mild to moderate symptoms. However, those with metabolic disorders like diabetes, heart disease, or obesity are more at risk for serious illness.

All viruses are spread through "piggybacking" on substances or processes vital to the cellular energy supply and metabolic pathways in the attacked body or other organisms.

The correlation between disease severity, metabolic disorder and high blood lipids (fats), was confirmed by observational studies on COVID-19 victims during the pandemic. However, metabolism is an individual process that is affected by many factors such as age, gender, lifestyle, and diet.

Metabolic pathways

Karolinska Institutet researchers have examined the energy supply of cells and their impact on the severity of SARS-CoV-2.

It is known that the COVID virus uses the metabolic pathway AKT/mTOR/HIF-1. This new study adds to this knowledge.

Researchers discovered that glutaminolysis and glycolysis are the preferred metabolic pathways by the virus when attacking the lungs. Both of these are crucial processes for cellular energy supply.

"The study shows that SARS-CoV-2 can infect lung cells when glycolysis and glutaminolysis are involved in its spread and growth," said Ujwal Neogi (researcher at Karolinska Institutet's Department of Laboratory Medicine). We can reduce viral production by blocking these pathways. In the blood plasma of patients with the most severe illnesses, we also found toxic metabolites such as glutamate and lactate.

A biomarker that measures the severity of the disease is one of the key findings of the study.

Shuba Krishnan, the first author of the study, said that mannose was a carbohydrate and a biomarker to severe COVID-19.

Blocking viral spread

Researchers say more needs to be done about elevated levels of toxic metabolites found in patients with severe illnesses.

Carl Johan Treutiger is a researcher at the Department of Medicine and Huddinge, Karolinska Institutet. He explains that "Changes to these metabolites could have lasting effects insulin resistance, neurocognitive disorders and organ failure." "The increased level of mannose may be linked to the risk of developing type II diabetes following COVID-19 infection."

Researchers are also looking into the possibility of a therapeutic strategy to stop viral spread via starving cells. This could be an effective treatment for the Crimean Congo haemorrhagic virus and a functional cure HIV-1.

These results were based on blood samples from 41 COVID-19 patients, which were analyzed using a variety of techniques, including plasma metabolomics. Researchers also examined the molecular pathway by which SARS-CoV-2 enters lung tissue.

Continue reading for more information about the cell response to SARS-CoV-2 infection

Shuba Krishnan et. al., Metabolic perturbation related to COVID-19 severity and SARS-2 replication. Molecular & Cellular Proteomics (2021). Information from the Journal: Molecular & Cellular Proteomics Shuba K. Krishnan et. al. Metabolic perturbation associated COVID-19 disease severity. DOI: 10.1016/j.mcpro.2021.100159