French tests on Covid drug offer hope for severe cases

A drug that could improve the outlook for patients with severe cases of Covid-19 - by slowing down the often-fatal “cytokine storm” condition - has been successfully tested in France.

28 April 2020
Preliminary trials of immune system drug tocilizumab suggest it could help severely-affected Covid-19 patients, said the AP-HP
By Connexion journalist

On Monday April 27, Paris hospital group l’Assistance Publique-Hopitaux de Paris (AP-HP) announced that preliminary trials of immune system drug tocilizumab (from laboratory Roche) suggested that it “significantly improves the prognosis of patients with mild-to-severe Covid pneumonia”.

Major improvements were noted in the 65 patients treated by tocilizumab, when compared to the control group.
The results are similar to those found in another early trial in China, but will now need to be replicated by further independent tests.

Yet, AP-HP said: “Given the context of the pandemic, the researchers and lead felt obligated, from an ethical point of view, to communicate this information, pending evaluation by peers, while also continuing caring for these patients.”

The clinical trial is part of ongoing work aiming to halt the so-called “cytokine storm” effect, which is an often-fatal hyperinflammation condition, caused when the patient’s immune system overreacts to an infection.

Cytokines are proteins that help the body to beat infection; but in some people, excessive levels are released (especially when the virus enters the lungs), causing an often fatal level of inflammation. This is known as a “cytokine storm”.

It can happen suddenly in patients that previously appeared to be improving.

Most people who are infected by SARS-CoV-2 - the virus that causes Covid-19 - have few symptoms, or a very mild case. But between 5-15% patients require hospitalisation, and develop a severe form of the illness, causing acute respiratory distress, where the lungs can no longer supply enough oxygen to vital organs.

The majority of these patients - 80% - have underlying risk factors.

“[But] this means that around 20% of patients of all ages, without risk factors, develop a severe infection, for no apparent reason,” said Anne Goffard, virology professor of the pharmacy faculty at the CHU Lille hospital.

“That is what is surprising about this infection. In certain people, it causes a secondary phase of an excessive and abnormal, poorly-controlled immune and inflammation reaction.”

This can then cause failure not only in the lungs, but also in the neurological system, kidneys and cardiovascular system.

This “cytokine storm” phenomenon was also observed during previous coronavirus outbreaks, including SARS (severe acute respiratory syndrome) in 2003, and MERS (Middle East respiratory syndrome) in 2012. It is also a risk factor among transplant patients.

Other trials into the same condition in France - by the French clinical trial platform Corimuno-19 - include tests using the drug sarilumab (brand name, Kevzara), which is normally used to treat rheumatoid arthritis. The immune system drug anakinra (Kineret) is also being tested, as is eculizumab (Soliris).

Corimuno-19 is a grouping of around 30 French research centres. It has already recruited 700 patients, and is testing six different drugs.

These trials include using a variety of different drugs on groups of severely-ill patients, and comparing the results to a control group being treated with existing treatments.

Epidemiologist Philippe Ravaud, who designed the original AP-HP research, told newspaper Le Monde: “In this urgent situation, the idea is to reposition medicines that already exist, which are already available in sufficient quantities to be given on a large scale, if they are proven to be effective.”

The trials look at the patients who respond the best, with this data then being used to refine further trials.

Similar tests are ongoing at hospitals in Marseille, including a clinical trial by the French company Innate Pharma, using the antibody drug advoralimab, when compared to a placebo.

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