2023-11-15 11:45:44
The COVID-19 disease, due to infection with the SARS-CoV2 virus, became an international pandemic in 2020. To date, more than 770 million people have suffered from this disease and almost 7 million of them have lost their lives. The most common cause of death in the group studied is lung involvement with consequent respiratory failure. However, there is still much to know about the targets of the virus in the lung and the mechanisms by which lung tissue can cease to be functional in the disease.
In a new study, published in CHEST, the official journal of thoracic doctors in the United States, a group made up of, among others, Aleix Noguera-Castells and Manel Esteller, both from the Josep Carreras Leukemia Research Institute (IJC), has proven that COVID-19 caused profound epigenetic changes in the lungs of patients who died from the disease. These alterations especially affected genes related to hyperinflammation and fibrosis.
In the study, researchers analyzed a large collection of lung autopsy samples from patients who had died from COVID-19 and compared them to healthy lungs from people who died from other unrelated diseases. The comparison of the DNA between both groups showed epigenetic differences in more than 2,000 points of regulation of the genetic material. A detailed analysis revealed that these were genetic sequences mainly associated with the promotion of a state of hyperinflammation, such as the overproduction of interferons and chemokines, chemical signals used by the immune system to promote inflammation.
Epigenetics would be like the control layer that a cell uses to precisely configure whether a gene will be active or not, without modifying its genetic information. Alterations in the epigenetic program of a cell can cause it to behave differently than expected, with organic consequences such as those observed in the study. Researchers from Lund University (Sweden) and the Ramón y Cajal University Hospital in Madrid (Spain) have also participated in the research, led by the IJC.
Dr. Esteller, director of the Josep Carreras Leukemia Research Institute (IJC), ICREA research professor and professor of genetics at the University of Barcelona, is confident that this new information can be useful in the clinical management of patients with COVID-19 and states that “knowing the mechanisms associated with death from COVID-19 caused by lung involvement can identify targets for drugs and medical interventions that prevent lethal outcomes in frail patients, and can also serve to prevent the progression of other viral diseases that affect the lungs.”
From left to right: Manel Esteller, Veronica Davalos, Aleix Noguera-Castells and Eva Musulen, from the Josep Carreras Leukemia Research Institute and co-authors of the study. (Photo: Josep Carreras Leukemia Research Institute)
The study’s findings may help doctors predict disease progression more confidently and allow for more effective treatment of patients in the clinic. As Dr. Esteller emphasizes, “two consequences of this study that should be evaluated are, on the one hand, the use of epigenetic drugs to prevent the progression of this and other viral diseases in patients susceptible to worsening; and, on the other, The possibility opens up that the molecular lesions found in these lungs could also be related to the so-called persistent COVID-19, in which perhaps these alterations have not been “cured” correctly, although without reaching the extremes of COVID-19. lethal”. (Source: Josep Carreras Leukemia Research Institute)
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