A group of Brazilian researchers has uncovered one of the factors that make Covid-19 more severe in diabetic patients. As laboratory experiments show, the higher blood glucose content captured by a type of defense cell called a monocyte and serves as an extra energy source, which allows the new coronavirus to replicate on a larger scale than in a healthy organism.
As a way of increasing the viral load, the monocytes start to release a large amount of cytokines – proteins with inflammatory action – that cause a series of effects, such as the death of lung cells.
The study has the support of Fapesp – Fundao de Amparo Pesquisa do Estado de So Paulo – and is led by Pedro Moraes-Vieira, professor at the Biology Institute of the State University of Campinas (IB-Unicamp), and by researchers who are part of the task against the university’s Covid-19, coordinated by professor Marcelo Mori.
The article is in the process of being Cell Metabolism, but it is already available in preprint version. Regarding the research, Moraes-Vieira states: “The work shows a casual relationship between increased glucose levels with what has been seen in the clinic: greater severity of Covid-19 in patients with diabetes”.
Using bioinformatics tools, the researchers initially analyzed public pulmonary cell data from patients with medium and severe Covid-19 conditions. The scientists observed an overexpression of genes involved in the alpha and beta interferon signaling pathway, which is linked to the antiviral response.
In the lungs of critically ill patients with Covid-19, the researchers observed a large number of monocytes and macrophages, two defense cells and control of the organism’s homeostasis. Monocytes and macrophages were the most abundant cells in the samples, the analyzes showed that the so-called glycolytic pathway, which metabolizes glucose, was considerably increased.
The analyzes by bioinformatics were carried out by the researchers Robson Carvalho, professor at the Botucatu Biocincias Institute at the Universidade Estadual Paulista (IBB-Unesp), and Helder Nakaya, professor at the Faculty of Pharmaceutical Sciences at the University of So Paulo (FCF-Usp).
The Unicamp group carried out a series of tests with monocytes infected by the new coronavirus, in which they were grown in different concentrations of glucose. The experiments were coordinated by José Luiz Proena Mdena, professor at IB-Unicamp supported by Fapesp and co-author of the research.
Coronavirus.Photo: 4X-image / iStock
“The higher the concentration of glucose in the monocyte, the more the virus replicated and the more the defense cells produced molecules such as interleukins 6 and 1 beta and the tumor necrosis factor alpha, which are associated with the phenomenon known as cytokine storm, in that it’s not just the lung, like the whole organism, that is exposed to this uncontrolled immune response, triggering several systemic changes observed in critically ill patients and that can lead to death “, stated Moraes-Vieira.
The researchers then used a drug known as 2-DG on infected cells, used to inhibit glucose flow. The treatment completely blocked the virus, as well as the increased expression of the previously observed cytokines and the ACE-2 protein, the one by which the virus invades human cells.
The results that showed greater activity of the glycolytic pathway before infection were obtained by means of protein analyzes of the infected monocytes.
Finally, the analyzes showed that the mechanism was mediated by the factor induced by hypoxia alfa I. As analyzed in several diseases, it is known that this pathway is kept stable, in part by the presence of reactive oxygen species in the mitochondria, the cells’ power plant. .
The scientists then used antioxidants in the infected cells and saw that hypoxia I alpha decreased their activity and, thus, stopped influencing glucose metabolism. This stopped the virus from replicating in the monocytes, the infected defense cells, which no longer produced cytokines toxic to the organism.
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