Genetic factors associated with inflammation predict covid-19 severity

BarcelonaIt is only 15 months since the SARS-CoV-2 coronavirus infection was declared a global pandemic. Although in science this period of time is usually considered very short, basic research has advanced fast enough to initiate a global vaccination campaign, advance in the knowledge of candidates for new drugs to fight the disease and identify risk factors that help determine which patients will evolve worse and, therefore, need more intense medical attention. Manel Esteller, Icrea researcher and director of the Josep Carreras Leukaemia Research Institute (IJC), and Aurora Pujol, also an Icrea professor and head of the Neurometabolic Diseases Group at the Bellvitge biomedical campus, have added to the already known list the first epigenetic markers associated with the severity of the disease. The results of their research have been published today in EBiomedicine,The Lancet's sister publication for laboratory findings.

The result is significant. Firstly, because it is a disease with an enormous variability that means that while some patients are asymptomatic without any apparent clinical manifestation, others evolve to suffer serious respiratory and circulatory complications. Secondly, the underlying reason for this variability is unknown, which makes it difficult to predict how patients will evolve.

So far, factors considered to be risk factors have been identified. Age or the existence of previous pathologies such as cardiovascular disease, obesity, diabetes or immune defects aggravate the diagnosis and make a worse evolution foreseeable. But none of this gives information on the rest of the population, which makes it difficult to determine who will need hospital treatment or require outpatient follow-up, explains Esteller. "Epigenetic markers could perform this function," he says. Overall, epigenetics regulates whether genes are expressed or not. In a way, they act as a switch that activates or inactivates the function of a gene. As a general rule, this mechanism is conditioned by external factors, such as hormonal and environmental factors.

13% of cases

The research coordinated by Esteller and Pujol concludes that there are epigenetic modifications associated with genes involved in an excessive inflammatory response and in others associated with a general tendency "to a worse state of health". The results are consistent with the 13% of the world's population that is estimated to have the same characteristics, "the same epigenetic signature," which they have named Epicovid, the researcher explains.

Pujol and Esteller maintain that it is precisely this segment of the population that should be of "special concern". These are patients who do not belong to the majority risk groups but who are asymptomatic or have mild symptoms, as well as those who have required hospitalisation without having a specific risk factor.

The study describes that in this type of patients, those positive for the virus who developed severe covid, it is possible to identify epigenetic variations in the chemical switches that regulate DNA activity. This genetic signature could account for 13% of cases. An analytical tool would help discriminate who is at risk of severe disease beyond known risk factors.