As the Covid-19 epidemic continues around the world after almost two years, scientists continue to study the molecular and genetic characteristics of patients developing severe forms of the disease. To date, scientific data do not allow us to specify the reasons why certain young patients without any particular health problem will develop into a critical form of the disease requiring in particular intensive care. Recently, work carried out jointly by French and American researchers has made it possible to highlight a gene signature of severe forms in young patients without comorbidity, thanks to the power of artificial intelligence. Explanations.
Covid-19, a very heterogeneous disease clinically
Over the weeks and months, researchers are still discovering a little more about the pathological mechanisms of Covid-19. One of the key points is to understand how to distinguish precisely the patients, especially young and without risk factors, who will develop a severe form of the disease likely to require an admission in intensive care and an intubation, from those who will present only an asymptomatic, mild or moderate form.
While certain comorbidities or age clearly constitute risk factors for developing a severe form, some young patients without health problems will develop unfavorably and justify invasive intensive care. However, mortality in these patients is still high today. It is therefore essential for healthcare teams to be able to identify these patients very early, in order to prevent the worsening of symptoms, particularly respiratory symptoms.
Young patients without comorbidity, but hospitalized in intensive care
In this context, French and American researchers used the latest techniques of artificial intelligence to analyze complex genetic characteristics, virological, immunological and serological of 72 patients hospitalized for Covid-19:
- Patients with severe forms, and developing in particular an acute respiratory distress syndrome, hospitalized in intensive care (47 patients);
- Patients without severe forms, hospitalized in a conventional sector (25 patients).
They chose to compare patient data all young (under 50) and without comorbidity, i.e. not initially considered to be at risk of developing a severe form of the disease. The data from these patients were compared with those from 22 so-called healthy control patients. Analysis of the data first unsurprisingly confirmed that acute respiratory distress syndrome was linked to a runaway immune system – which researchers call a cytokine storm – and an exacerbated inflammatory response.
Identification of a prognostic marker or even a new therapeutic target?
The power of artificial intelligence then made it possible to identify a network of 600 genes, which would be involved in the evolution to a severe form of Covid-19. Among these genes, five are said to be particularly overexpressed in patients admitted to intensive care for acute respiratory distress syndrome. One of these genes, the ADAM9 gene, interacts with SARS-CoV2. The overexpression of this gene would be directly involved in the evolution towards an acute respiratory distress syndrome.
Through experiences in vitro, the researchers then found that blocking the ADAM9 gene in infected lung epithelial cells allowed :
- A decrease in the presence of the SARS-CoV2 virus in cells;
- A reduction in virus replication.
This gene could therefore constitute a therapeutic target interesting for reducing the risk of severe forms of Covid-19. Monoclonal antibodies targeting this gene have already been developed and are currently being tested in oncology. If their interest against Covid-19 is confirmed, it would therefore be possible to test them in this new indication.
Such a study made it possible to demonstrate a true gene signature of patients developing severe forms of the disease, without any previous risk factor. It has also demonstrated a potential therapeutic target against the disease.
Estelle B., Doctor of Pharmacy