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Anticipating the Severity of COVID-19 to Improve Treatment

Studying the dysregulation of the immune system caused by the HLA-G antigen

Some patients with severe cases of SARS-CoV-2 experience a strong and sudden dysregulation of their immune system. The immunology research team at the François Jacob Institute of Biology (CEA) and the U976 HIPI unit (Saint-Louis Hospital) in Paris are studying the role played by the HLA-G molecule in the immune system, a molecule for which they are the world's leading experts. While the molecule can play a harmful role initially, it is beneficial for controlling the cytokine storm at a later stage. The project aims to provide a better understanding of the virus's physiopathology, uncover new information about the uncontrolled immune response observed during the SARS-CoV-2 infection and propose new treatment options for better patient care.

Project Identity

Project Initiator: CEA/François-Jacob Institute of Biology Year(s) of support: 2020-2021
Support provided: funding of the analytical work (assaying, sequencing, genetic transcription) and of a portion of the salary for a research technician. Amount provided: 158,000 euros
Location: Saint Louis Hospital, Paris, France

Air Liquide Monitoring manager: 

Géraldine Farjot, Air Liquide Santé International

 

Anticipating to Improve Treatment

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.

Positive and Negative Effects of HLA-G

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.

Did you know?

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.