Coronavirus: AP-HP launches new clinical trial to counter the "inflammatory storm"

How do you prevent the sudden worsening of symptoms experienced by some Covid-19 patients after a few days? A clinical trial has just been launched as a matter of urgency by the Assistance Publique - Hôpitaux de Paris (AP-HP) to find a solution against what specialists call an "inflammatory storm".

"The researchers believe they have identified a certain number of targets" to combat this phenomenon, said Thursday, April 2, Professor Philippe Gabriel Steg, vice-president in charge of research within the executive board of the AP-HP. Out of some 130 projects received by the Ile-de-France organization, "we have pre-selected 35 and five have already started," explains this cardiologist from Bichat hospital in Paris.

The AP-HP, which brings together 39 hospitals, is also collaborating in trials coordinated by other organizations, such as the European study Discovery led by Inserm, which assesses the effectiveness of four drugs or combinations of drugs against Covid -19 (the antiviral remdesivir, the anti-HIV drugs lopinavir and ritonavir, alone or in combination with interferon beta, and hydroxychloroquine).

Antibody administration

But the trial launched this week, called Corimunno, is exploring other treatments, with a different strategy against Covid-19. "Most of the treatments that will be tested are drugs directed against the excessive immune and inflammatory reaction which occurs very suddenly, often a week after the onset of symptoms", a phenomenon "called an inflammatory storm or cytokine storm", since the body begins to produce "excessively" pro-inflammatory proteins called cytokines, continues Professor Steg, quoted by AFP.

To regulate this reaction, the researchers will in particular administer to the participants monoclonal antibodies - antibodies created in the laboratory, from a single strain of lymphocytes and designed to respond to a specific target.

The first one to be tested, sarilumab, is being developed by Sanofi and Regeneron. It is currently used in the treatment of rheumatoid arthritis. The two laboratories have already launched a trial in the United States in mid-March, involving 400 patients, to see if it could play a role in the inflammatory response of the lungs of patients severely affected by Covid-19.

Another immunosuppressive monoclonal antibody directed against the same target, tocilizumab (Actemra or RoActemra), from the Roche laboratory, is also the subject of several clinical trials around the world to judge its usefulness against the coronavirus.

The stem cell track

AP-HP researchers are also exploring other treatment options for acute inflammation of severe forms of Covid-19: a trial has just been launched on Thursday at La Pitié-Salpêtrière hospital in Paris to see if injecting certain stem cells from the umbilical cord (mesenchymal cells) can reduce lesions in the lungs of patients with acute respiratory distress syndrome. It will include 60 patients currently placed on artificial respiration in seven Parisian intensive care units.

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"These cells have already been used in humans in multiple pathologies which have a strong inflammatory component, for example autoimmune diseases, certain complications of bone marrow transplants intended to treat blood diseases, heart failure or liver pathologies, ”explains the AP-HP, adding that their“ excellent tolerance ”has already been demonstrated.

"These cells also have the advantage of multiplying rapidly in culture, which allows significant production" which can then be frozen and stored. Other trials will start soon, to test in particular the effectiveness of the anti-inflammatory drug naproxen or even converting enzyme inhibitors, drugs used for a long time against hypertension and heart failure.

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