“The story of the epidemic is far from over”

Étienne Decroly is a biochemist, research director at the CNRS, at the University of Aix-Marseille, and a member of the French Society of Virology. After research on HIV, he is currently working on the replication mechanisms of emerging viruses, and in particular the way in which viruses are able to disguise their genome to go unnoticed in human cells.

Why is it so important to understand the origin of an epidemic?

This question may seem of minor interest because, in the emergency of the pandemic, the challenge is first of all to develop therapies and vaccines in order to protect the population. But if we want to avoid repeating similar situations in 10 to 15 years, we need to understand the mechanisms underlying the emergence of Sars-Cov-2 in humans. In 20 years, this is the third time that a highly pathogenic virus from this family has emerged (with Mers-Cov and Sars-Cov-1, editor’s note).

It is therefore an important research question…

Regarding the origin of Covid-19, the scientific community unanimously considers that there are natural viruses circulating in the animal reservoir that are bats. In 2020, the Wuhan Institute of Virology published the genome of the RATG13 virus, a cousin of Sars-Cov-2, identified in Yunnan province, 16 km from Wuhan. However, it seems that this virus is not able to effectively infect human cells. In February 2021, the Pasteur Institutes of Laos and Paris identified, in Laos, a virus closer to Sars-Cov-2. This virus is potentially capable of crossing the species barrier because it can infect human cells, therefore going from the bat to the human.

These tangible elements, however, do not allow us to understand how Sars-Cov-2 emerged in the city of Wuhan. Two main hypotheses are possible: either it is a zoonosis, or the emergence of this virus is linked to a research accident. The question is not resolved because there is a lack of elements demonstrating one or the other hypothesis. That of zoonosis has long been favored because it is the usual mechanism of viral emergence.

But the likelihood of the virus jumping from bats to humans is limited…

Indeed, for two reasons: humans rarely visit the caves where they proliferate; the bat virus receptor is genetically different from humans. The researchers propose that these viruses pass through an intermediate host. Due to deforestation, for example, bats find refuge in sheds used for breeding and infect these animals.

The risk of zoonosis is increased when the virus spreads in farms because breeders are in daily contact with these animals… Thus, viruses end up reaching the human species. This hypothesis was, at the start of the pandemic, the most probable hypothesis. However, for the moment, despite our genome sequencing capabilities, there is no evidence that an intermediate host was involved in the species barrier crossing of Sars-Cov-2.

Can the virus get out of the Wuhan lab?

The research accident hypothesis is a subject of debate. You should know that these viruses are studied in laboratories with a security level below P4. Studying these viruses involves collecting samples from caves, analyzing the samples, culturing the viruses, and experimenting in animal models. Each stage carries specific risks. This hypothesis has not been evaluated in detail by the WHO.

Were you surprised at how quickly the virus spread from January 2020?

From the beginning of January 2020, we observed the speed with which the virus was spreading among the Chinese population. We superimposed the curves with those of Sars-Cov-1 and immediately understood that controlling the epidemic would be extremely difficult if drastic measures were not taken quickly. We immediately focused on the genome of this virus in order to begin new studies.

Are there possible comparisons with the appearance and spread of HIV?

Stories from other outbreaks can shed light on viral emergence processes. The major differences between HIV and Sars-Cov-2 are as follows: the latter is respiratory, so controlling the spread is much more complex; it causes an acute infection most often well controlled by the immune system. HIV is very different because it is a chronic sexually transmitted infection. The best comparison model therefore remains that of influenza viruses.

Should we fear new variants, or even a more virulent variant than Omicron?

The story of the epidemic is far from over. The virus still circulates in populations that are still insufficiently immunized. Three scenarios are possible: the first is that we remain in a very tense situation in terms of hospitalizations, with significant circulation and therefore the appearance of new variants, potentially more transmissible and more dangerous.

The second intermediate scenario is that the vast majority of people who have been contaminated by Omicron or vaccinated in Europe, we can think that immunity allows us to better control the infection. In this case, there could still be waves but with a controlled level of hospitalizations. The third hypothesis is that, collective immunity being good, we are temporarily rid of the virus and return to normal life.

What is your preferred hypothesis?

Studies show that immunity induced by vaccines or natural infection is not long-lasting enough. In this context, it is difficult to imagine that the epidemic will end today. In Europe, I think we are heading towards a seasonal disease with peaks in the fall-winter. This implies keeping barrier measures and continuing the development of drugs, research in “vaccinology” to have more effective vaccines, especially against infections.

Will it be necessary to redo an injection next winter?

It’s complex. Clinical studies show that vaccines adapted to Omicron are not completely effective. By adapting the vaccines to the variants, we may be able to broaden the spectrum of the antiviral response. My hypothesis is that we are moving towards vaccinations for populations at risk, with injections adapted to the variants, as we already do for the flu. I hope that vaccination will return to the bosom of medicine and get out of the compulsory vaccination policy which is showing its limits. It is up to doctors to assess the risk-benefit for each patient.

What will be, in the future, the role of drugs to treat this disease?

The vaccine as we know it today will not be enough. It’s necessary develop a therapeutic arsenal against these viruses. Significant research efforts for the development of drugs must continue, and this requires funding. There are already two or three effective antivirals on the market and many molecules make it possible to control the inflammatory aspect of the disease.

How do you see the gradual lifting of restrictions?

We need a more rational approach, defining the conditions necessary for removing the masks, with objective scientific criteria. Having 300 deaths per day linked to a viral disease is not a return to normal, not to mention the multiplication of long Covids.

Can Covid-19 ever disappear?

This is not my working hypothesis. Different animal species are infected by the virus, cats, dogs, deer, and can constitute reservoirs. This offers the virus opportunities for evolution and the possibility of new emergences.

Mini glossary
Epizootic: an epidemic that strikes animals.
Zoonosis: infectious disease of vertebrate animals that can be transmitted to humans, such as rabies, for example.
Sars-Cov-2: name of the virus responsible for the Covid-19 pandemic. It belongs to the family of coronaviruses.

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