The work led by Nathalie Rouas-Freiss and overseen by Professor Carosella aims to anticipate the severity of the SARS-CoV-2 infection in order to provide more effective treatments to patients with severe cases.

The research team is working to improve:

• our understanding of the immune system modulation caused by SARS-CoV-2

and

• follow-up care for COVID-19 patients, especially by detecting biomarkers that can predict changes in the disease

The team is focusing their research on the molecule for which they are the world's leading experts – the HLA-G molecule, which is present at elevated levels in cells infected by the virus.

HLA-G is short for human leukocyte antigen¹. This molecule is known to inhibit the function of immune cells by interacting with the receptors present on the immune cells. As a result, it limits the duration and intensity of the immune reaction - known as the immune checkpoint. 

The researchers aim to test the hypothesis that HLA-G can play both a harmful and beneficial role in the progression of COVID-19:

• In the first stage of the infection: when a fast, effective antiviral immune response is needed, the molecule blocks the immune system
• In the second stage of the infection: during the hyperinflammatory syndrome (cytokine storm) experienced by certain patients with severe cases, HLA-G controls and limits inflammation

If the level of immune system dysregulation caused by HLA-G does in fact correlate to the level of severity of the disease:

• the immune checkpoint can be taken as a predictive biomarker for the progression of the disease
• patients who are likely to develop severe cases of COVID-19 can be identified

The researchers will study the immune parameters of more than one hundred COVID-19 patients admitted to the hospital during the first weeks of the disease by targeting the HLA-G molecule and its receptors, as well as the receptors for the SARS-CoV-2 coronavirus. One segment of the patients comes from the retrospective COVIDeF² cohort, while the other segment is currently enrolled in the research program thanks to the partnership with Professor Olivier Brugière, a pulmonologist at Foch hospital.

HLA-G plays a beneficial role during pregnancy: it helps the mother's body tolerate the fetus, which is initially considered a foreign object. Another beneficial application: organ transplants. The higher the levels of HLA-G on the transplant and circulating in the blood, the better the transplant is tolerated by the body. 

On the other hand, this molecule is found in large quantities in cells implicated in pathologies such as cancer and during infections of viruses like the flu. By blocking the immune system, HLA-G enables tumors and viruses to spread.

^{1 An antigen is a natural or synthetic macromolecule that is recognized by the antibodies or cells of an organism's immune system and has the ability to trigger an immune response.
2 Cohort of patients hospitalized in Ile-de-France during the first wave of COVID-19 in the spring of 2020.}