Research teams around the world are working to better understand the coronavirus (2019-nCoV), identify an effective treatment and develop a vaccine. Professor Arnaud Fontanet, who heads the research and expertise unit in epidemiology of emerging diseases at the Institut Pasteur in Paris, analyzes the characteristics of the virus and reviews the evolution of knowledge of this epidemic.
Do you know today about the characteristics of the virus?
At the very least, very strong presumptions. Estimates converge to an average coronavirus incubation time of six days with a maximum of twelve days. This is important because it means that the quarantine for fourteen days, recommended by the World Health Organization (WHO) and in particular applied to French returnees, is sufficient to detect people who have been infected. We also have more visibility on the transmissibility of the virus. It is estimated today that an infected person infects two others in the absence of protective measures, such as wearing a mask and rapid isolation. The idea is to drop the reproduction rate below 1. On this condition, the epidemic would be under control. In addition, it also seems that patients are only truly contagious from the moment they show symptoms of the disease, fever, cough and difficulty breathing. There have been reports of coronavirus transmission before the onset of these symptoms. But they are very rare. For epidemiologists, this information is essential, since the effectiveness of prompt isolation of suspect cases depends on it.
According to Chinese authorities, the virus has already killed more than 810 people in China. How many more victims will he make?
It’s too early to know. In the event of an unfavorable course of the disease, patients go through several phases: they often first declare pneumonia, which degenerates into acute respiratory failure, followed by secondary bacterial infections. Death can therefore occur after two to three weeks. This means that many sick people may succumb in the days to come. It also depends on the number of people actually infected. Some who may have reported mild forms of the disease may not show up at the hospital and continue to spread the virus. Infected persons who present themselves are no longer automatically declared positive due to the lack of sufficient diagnostic tests. In reality, Chinese authorities are struggling to cope with a health crisis of such magnitude (read page 3). According to a modeling team from the University of Hong Kong, there are today around 100,000 infected people in China, while the authorities have managed to count only 25,000. On the part of the Chinese, it is likely more logistical difficulties than a desire to conceal which explains the delay in counting cases.
Is this new coronavirus more or less dangerous than SARS?
It all depends on what you watch. 2019-nCov is less lethal than SARS, however it is difficult to control its transmission. The SARS epidemic had affected 8,000 people, all of whom reported severe forms of the disease, and caused 774 deaths. The current Chinese virus has already affected many more people than the SARS coronavirus, so that at the end of this new epidemic, the number of deaths will probably be much higher than with SARS.
A document from the Institut Pasteur in Shanghai, relayed by a Thai magazine, mentions a possible mutation of the virus, which would become stronger and more virulent.
I have not seen the publication you are talking about. A recent survey by this institute identifies scientific research conducted almost everywhere. The ability of the virus to mutate is mentioned. But it is likely that the coronavirus is evolving. It is an “RNA” virus, which makes copy errors when it replicates: these are called mutations. This can allow him to adapt. If this is the case, all scenarios are possible: the virus could be more easily transmitted, but not necessarily more virulent. An American site, Nextstrain.org, is closely monitoring the evolution of the different identified strains of the virus, which will allow correlation of the mutations observed in the behavior of the virus in the population.
Chinese researchers have claimed to have developed an “effective treatment”. For its part, the WHO has stated that there is no therapy. Who to believe?
I saw that. This Chinese laboratory has no doubt succeeded in inhibiting the growth of the virus in a test tube. But all researchers know that this type of result is not convincing. What works in a test tube is not necessarily, and far from it, in humans.
What treatments are currently being administered to patients?
Several existing molecules, but with other therapeutic indications, are today administered to Chinese patients. This is the case for drugs used in triple therapy for HIV, such as lopinavir-ritonavir. For its part, WHO is bringing together experts to propose a trial by lot so as to test several molecules in parallel. The list is not yet known, but interferon, an antiviral molecule naturally produced by humans, lopinavir-ritonavir and Remdesivir should be included. These molecules had already been used during the SARS and SEA epidemics, so much so that we know their toxicity profile, their side effects on humans. If one or more of them works on the 2019-nCoV, this will allow them to go much faster in their use. Another approach to get treatment is from a test tube, so from scratch. Researchers are doing it all over the world. But it can take a year or two to get an effective medication.
Are there other tracks in progress?
Some researchers have decided to work with monoclonal antibodies. Basically, it is about taking the blood from healed people and extracting the antibodies that allowed it to neutralize the coronavirus. They are then produced in large quantities, which are then administered intravenously to patients. An American company, Regeneron, is exploring this path today. The Pasteur Institute also, within the framework of Reacting, a collaboration platform between several French research institutes, such as Inserm or public assistance hospitals.
A British researcher, Professor Robin Shattock, has announced that his team is ready to launch an animal test phase this week to test a new vaccine against the coronavirus. Is it credible?
This is important, but keep in mind that it takes at least one to two years to develop and distribute a new vaccine.
Where are we at research on this possible vaccine?
Lots of teams are working on it. The Coalition for Epidemic Preparedness Innovations (Cepi), a US public-private partnership, has selected three “vaccine candidates”, whose production it believes will be the fastest. At the Institut Pasteur, we are working on a technology used for a chikungunya vaccine which we are trying to adapt to the coronavirus. In this case, the measles vaccine is used in which coronavirus genes are inserted so as to stimulate the immune response against it. We should be able to test the product in late 2020 in animals and in 2021 in humans. Once a vaccine has been developed, produced for clinical trials and shown to be effective, it can be produced on a large scale. The major laboratories are experienced there.
What is your biggest concern today?
The coronavirus is now present in 28 countries, although its spread outside of China is contained. It would be much more problematic if it started to develop in countries with fragile health structures. This would be true in India, where three cases have already been identified. This would undoubtedly also be the case in sub-Saharan Africa. And the risks are far from zero in view of its important trade relations with China. African countries (1) are just as worried as we are. The influenza surveillance networks have been reactivated there for the occasion and are called upon to be extra vigilant when they are confronted by people with breathing difficulties and / or likely to travel to China.
(1) To help them, the Institut Pasteur de Dakar is holding a workshop from February 6 to 8 where technicians from 15 African countries are trained in virus detection.
Nathalie Raulin
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