They discover more than 20 genetic variants that predispose to severe COVID

The world’s largest genetic study on COVID, in which more than 57,000 people have participated, has revealed more than 20 genetic variants that predispose to suffering from the severe form of the disease, findings that will help develop new treatments and prioritize some therapies.

The results of the investigation were published this Monday in “Nature”.

The severe form of COVID-19 causes lung damage mediated by the patient’s immune system, but while some people die, others do not develop any symptoms. The difference between one and the other lies in genetic factors that scientists are just beginning to understand.

For this study, researchers from the GenOMICC consortium, a global collaboration for the genetic study of diseases, led by the University of Edinburgh in collaboration with Genomics England, sequenced the genomes of 7,491 patients from 224 intensive care units in the United Kingdom.

They then compared them with those of 48,400 other people who had not had COVID-19, participants in Genomics England’s 100,000 Genomes project, and with those of another 1,630 people who had mild COVID.

This allowed them to identify 16 new genetic variations linked to the severe form of COVID, some of them related to blood clotting, the immune response and the intensity of inflammation.

In addition, they confirmed the involvement of seven other genetic forms that had been discovered in previous studies.

A big step in the search for treatments

The study reveals that one of the variants, which alters a key messenger molecule in immune system signaling – called interferon alpha-10 – is sufficient to increase a patient’s risk of severe disease.

This finding not only reveals the importance of this gene in the immune system, but also suggests that treating patients with interferon -proteins released by immune cells to defend themselves against viruses- could help control the disease in its early stages.

The study also discovered that variations in the genes that control the levels of ‘factor 8’ (a central component of blood coagulation) are associated with the critical form of covid, which could explain some of the coagulation abnormalities that they suffer. the most severe cases of this disease.

“The study explains why some people develop severe COVID and others do not have any symptoms, but more importantly, it gives us a deep understanding of the disease process and is a big step forward in finding more effective treatments”, highlights Kenneth Baillie , an expert in Critical Care Medicine at the University of Edinburgh.

For the medical director of Genomics England, Rich Scott, “study illustrates importance of whole genome sequencing to detect rare and common variants influencing critical illness requiring intensive care”.

Changes in areas associated with smell and memory

Also today, “Nature” publishes another article that describes the changes that SARS-Cov-2 infection produces in the human brain (including in areas associated with smell and memory), although the authors warn that in order to know if these effects persist in the long term , or if they can be partially reversed, further investigation is needed.

Gwenaëlle Douaud’s team at the University of Oxford investigated changes in the brains of 785 UK Biobank participants (aged 51-81) who underwent two brain scans, an average of 38 months apart. , and cognitive tests.

401 tested positive for SARS-CoV-2 infection between the two scans (15 were hospitalized), and 384 were age- and sex-matched controls.

The authors identified several long-term effects after infection, including further thinning of gray matter in the orbitofrontal cortex and parahippocampal gyrus (regions associated with smell and memory).

In addition, those with COVID had evidence of tissue damage in regions associated with the olfactory cortex and a reduction in brain size.

On average, the infected patients also showed greater cognitive decline, associated with atrophy of a brain region known as the cerebellum.

The authors also performed a control analysis in people who developed non-COVID-related pneumonia to show that these changes were due to the coronavirus and not respiratory disease.

These findings may indicate degenerative spread of COVID, either through olfactory pathways, inflammation of the nervous system, or lack of sensory input due to loss of smell.