Caregivers around a patient with Covid-19, in Montreuil (Seine-Saint-Denis).
©BERTRAND GUAY / AFP
Besides the vaccine
In addition to vaccines, treatments against the symptoms of Covid-19 have improved significantly over the past year. Many avenues for improvement are being studied.
—Atlantico: Vaccines are at the heart of the government’s strategy to fight the pandemic, but we can talk about treatments against the symptoms of Covid-19. Are they constantly improving since the start of the health crisis?
Morgane Bomsel: Absolutely. Since last year, we now know how to use corticosteroids and when to use them, which helps treatment a lot. There are also other kinds of treatment that help control the virus, but they may not be available everywhere. Monoclonal antibodies are thus validated either alone or in combination, but they are quite expensive and rather inaccessible for the hospital. They have been validated by the authorities, but it is not certain that enough has been produced because of their complixity. And now we have to analyze their action against variants, which is another problem.
Clinical research is also beginning to follow many tracks. It remains to be seen of course whether they will be validated in humans, but there is in any case a certain amount of research which we can hope that it will bear fruit. Among these avenues, we can cite antivirals, which will prevent the virus from multiplying. There is also a lot of research on antibodies. The idea is that by repositioning molecules that are effective against other pathologies, or even by developing new molecules, we can block the progression of the virus – for the moment at least in small animals.
There are also avenues aimed at the clinical stage further upstream, such as interferants which will limit the progression of the disease in relation to replication. These are avenues that are yielding encouraging results.
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Etienne Decroly : In antiviral strategies, there are two main avenues available:
- A first consisting in developing molecules that interact with the virus and prevent it from growing too massively.
- A second works when patients become ill. The disease is known to be linked to an over-reaction of the immune system with a cytokine storm. The storm is responsible for severe symptoms and if we control the storm and the inflammatory response better, we can prevent serious cases and eventually their death. These are supportive treatments making it possible to progress in the disease without controlling the virus …
Regarding antiviral strategies, unfortunately today very few molecules have proven their effectiveness. Only a few molecules have obtained their marketing authorization and this differs depending on the country, we find remdesivir or favipiravir. These two antivirals are homologs of nucleosides, a drug that comprises the genetic components of the virus. As the virus replicates, it will instead incorporate the natural nucleotide to take the drug and this will lead to multiplication errors.
The effectiveness of these compounds is very limited. Studies in animals have shown for a long time that in order to be effective, it is necessary to treat very early. Unfortunately, as these compounds are either complicated to administer because they are injectable, or difficult to administer because there are risks of toxicity of the compounds. It is impossible to systematically treat patients and the administration occurs too late for efficacy to be significant so there is very little effect.
Other treatments in development exist which will soon arrive on the market. The big difference is that the molecules are often new and under development. There is the polymerase (analogue of nucleotides and nucleosides), also protease inhibitors but they are not yet available. There has been a lot of hope for molecules, some of which induce antiviral activities in vitro in certain cellular systems. However, clinical trials have not shown significant efficacy. Either the efficacy / risk balance was not good, or the clinical efficacy was poor. If a compound were 100% safe, there would be no debate.
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Could these treatments be a first avenue to manage the infection?
Morgane Bomsel: It is difficult to say, but it will surely be an interesting avenue in addition to the vaccine strategy, which as such is a good strategy but faces a big problem of quantity of the doses produced.
Who are these treatments for?
Morgane Bomsel: To patients in whom attempts are made to prevent the development of severe symptoms. Anti-inflammatory drugs then block the progression of the disease. For a year, we have better understood the different phases of the infection and at each phase, we provide a specific treatment. On corticosteroids, there are thus several windows of effectiveness – but not at the beginning or at the end of the infection!
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Etienne Decroly : When patients are sick, we see the effects of a molecule more significantly. In the families of compounds that work, molecules regulating inflammatory responses deal with the hyperraction of the immune system. Some are in clinical trials and are working well. We also have support treatments because we know that there are coagulation disorders linked to the disease. By combining these molecules with anti-inflammatory drugs, we have relatively good results. Treatments with oxygenation also help to improve the treatment rate of intensive care patients. Thanks to this, the percentage of people who die in intensive care has greatly decreased.
Neutralizing antibodies are also arriving. They are similar to those found in the serum of patients infected with the virus. It is a subclass in the set of antibodies which will bind to the Spike protein and which blocks the entry of the virus into its cell and therefore its application. Different companies have identified specific antibodies and some will be available soon. The difficulty of this class being the appearance of the variant because the risk could be that these antibodies lose their effectiveness. When we let these pathogens run in nature, they will evolve and it will be more and more difficult to control.
Today, we hear many voices talking about miracle cures like ivermectin and others? Why do these people think they might be interesting? What do we know from a scientific point of view?
Morgane Bomsel: We always come to the subject of publications, which sometimes took place in small numbers and under specific conditions, with perhaps bias in the analyzes. Are the studies really conducted with a group of treated people compared to an untreated group? The treatments, to be sure that they are effective, must be validated on a large scale and pass before scientific commissions in addition to publications. Scientific journals may be of interest, but marketing authorization for a drug requires large-scale verification.
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On the market today, we mainly have anti-inflammatory drugs and monoclonal antibodies. There are other avenues in the pipelines, such as anti-inflammatory drugs on drugs that we are going to position, which could therefore go relatively empty if the molecules prove to be protective on a large scale. And, finally, at an earlier stage, other molecules are in development. It moves a lot!
Also (re) read our full interview with Etienne Decroly: While waiting for the vaccines: but by the way, where are the treatments for Covid-19?
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