COVID-19 causes epigenetic scars in the lung

Spanish researchers have determined that COVID-19 causes profound epigenetic changes in the lungs of patients who have died from the disease. Such alterations particularly affected genes related to hyperinflammation and fibrosis, leading to lung damage, respiratory failure and, eventually, death.

To date, more than 770 million people have suffered from COVID-19 and nearly 7 million have lost their lives. The most common cause of death in the studied group is lung involvement with consequent respiratory failure. However, the targets of the virus in the lung and the mechanisms by which lung tissue can cease to be functional in the disease are largely unknown.

Dr Manel Esteller, Director of the Josep Carreras Leukaemia Research Institute, led a group of researchers in analysing an extensive collection of lung autopsy samples from patients who died from COVID-19 and compared them with healthy lungs from people who died from other unrelated diseases. Comparison of the DNA between both groups showed epigenetic differences in more than 2000 regulation points of the genetic material; analysis revealed that these were genetic sequences mainly associated with promoting a state of hyperinflammation, such as the overproduction of interferons and chemokines — chemical signals used by the immune system to promote inflammation.

Epigenetics is the control layer a cell uses to finely tune whether a gene will be active or not, without modifying its genetic information. Alterations in the epigenetic program of a cell can make it behave far differently than expected, with organic consequences like the ones seen in the study.

“Knowing the mechanisms associated with death from COVID-19 due to lung involvement can [help] pinpoint targets for drugs and medical interventions to avoid lethal outcomes in fragile patients, and may also serve to prevent the progression of other viral diseases that affect the lungs,” Esteller said. Indeed, the findings — published in the journal CHEST — may help doctors predict the progression of the disease more confidently and allow for a more efficient treatment of patients in the clinic.

“Two consequences of this study to be evaluated are, first, the use of epigenetic drugs to prevent the progression of this and other viral diseases in patients susceptible to worsening; and second, it opens the possibility that the molecular lesions found in these lungs may also be related to the so-called long-term COVID-19, in which these alterations have not ‘healed’ correctly, but without reaching the extremes of lethal COVID-19,” Esteller said.

Image credit: iStock.com/SvetaZi