Conversation with Mircea Sofonea: "Today the spread of the virus is exponential"

Where is the epidemic situation in our country? What to think of the measures announced Thursday, March 18 by Prime Minister Jean Castex? The answers of Mircea Sofonea, lecturer in epidemiology and evolution of infectious diseases at the University of Montpellier.

The Conversation: You recently looked at variants V1 (from the B.1.1.7 lineage initially detected in the UK in September), V2 (from the B.1.351 lineage detected in South Africa in October), and V3 (from the P.1 lineage detected in Brazil and Japan in January), which are currently circulating in our territory. What did you learn from this work?

Mircea Sofonea: We analyzed the proportion of variants by age, by analyzing 40 RT-PCR data specifically targeting certain sites that allow us to determine whether we are dealing with one of these three variants, or with the “historical” strain, which circulated in our country before their imports. These analyzes were carried out on samples from the Cerba group's laboratory network, as well as from the Montpellier University Hospital, which enabled us to obtain information on the entire territory.

Analyzes show that since February 16, these three variants are probably responsible for more than half of infections in most regions of France. Although these RT-PCR data do not make it possible to distinguish the variant of Brazilian origin from that of South African origin (because the sites targeted by the analyzes are identical for these two variants), we see - as we can see. had seen in England - that these new variants have a propensity to be more present in the youngest: on the analyzed data, the proportion of infections caused by the variants decreased gradually with age, reaching a factor of two between 5 and 80 years old.

We were also able to calculate the effective reproduction number of the new variants, as well as that of the historical strain, for the months of January-February.

(Editor's note: The number of reproduction is an estimate, over the last 14 days, of the average number of individuals infected by an infected person. We speak of the basic reproduction number (or R0) at the start of the epidemic, in the absence of transmission control measures and when the population is fully susceptible to the virus. During the epidemic, this number changes: we speak of the effective or temporal reproduction number (Rt). If it is less than 1, the epidemic regresses, above 1, it progresses.)

If we consider that the reproduction number of the historical strain is 1, then that of all three variants is between 1,37 and 1,64 (95% confidence interval). We are currently carrying out more detailed analyzes on each variant, the V2 and V3 variants (respectively identified in South Africa and in Brazil) being probably less contagious than the V1 variant (identified in England).

This means that if these variants had been those circulating at the start of the epidemic, before the introduction of preventive health measures, their number of reproduction would not have been three, like that of the historic strain, but four. at least.

TC: What do you say to people who say that these variants have no influence on the dynamics of the epidemic, since it stagnated in France, or even declined in certain countries in February?

MS: We have indeed observed a stable plateau which can be explained simply: at that time, the historical strain was more impacted by the curfew measures. It was in decline, which may have given the impression that the epidemic was slowing down. But at the same time, the new variants, especially V1, were gaining momentum. This slowdown, while more transmissible viruses were circulating, may have seemed paradoxical on the surface, but the breakdown of the incidence between a historical epidemic in decline and a new one in progress resolves this paradox.

This is to a certain extent reminiscent of the scenario at the end of summer, when an increase in significant contamination was observed, without however the hospital dynamic being impacted: this is because the people who became infected were younger. . This rejuvenation of contaminations, linked to the relaxation of barrier measures during the summer among young people, generated a sort of statistical illusion when we were only interested in the number of cases. On the other hand, this disappeared when the age groups were taken into account. We saw what happened next in October: the virus spread to older people and hospitalizations started to rise again.

This is the whole difficulty of the study of this pandemic: it is necessary to remain in the quantitative analysis, without invoking hypotheses which have not yet proven biological support - contrary to what some “reassurance” have been able to do. which relied on a decrease in virulence, on plethoric false positives, or on a supposed "natural cycle of the virus". But we must not reason by pure analogy either: at the start of the pandemic, the scientific community based itself on knowledge of the 2002-2003 SARS epidemic, which led national and international observers to minimize gravity. People infected with SARS were not contagious when symptoms first appeared, and sometimes did not become so until five days later. With SARS-CoV-2, people are contagious before symptoms develop, and there are also people who are asymptomatic or paucisymptomatic ...

To return to the situation in February, we see that it was compatible with a drop in the historical strain and an increase in new variants, which were gradually becoming the engines of new epidemics. In addition, it should be remembered that the oscillations in the number of reproduction were low: we were still above 0,9, in other words in a dynamic that did not rapidly decrease the incidence, which remained fixed at a high level, and which was not likely to prevent a possible rebound.

Today, we have returned to a dynamic of epidemic progression with a reproduction number between 1,02 and 1,11 at the national level (calculated on admissions to critical care), i.e. a 50% increase in admissions in one month. . In itself, it is not explosive. However, in a context of already high hospital occupancy, the tension quickly becomes problematic in the critical care services of certain regions.

The Conversation: In addition, the more viral circulation increases, the greater the risk of the emergence of other variants?

MS: Exactly. But this question is not only national: resolving it would require coordination at the global level. However, it is certainly always better to avoid seeing the emergence of new variants on our soil, hence the classification by variant to follow from mutant detected in Lannion, in Brittany.
This raises the question of the global vaccination strategy: concentrating vaccination on certain countries, as is currently the case, does not prevent the emergence of a variant elsewhere. The idea should rather be to end the epidemic everywhere, because each source of infection constitutes an additional opportunity for SARS-CoV-2 to mutate and generate a new line that is more contagious or capable of escaping vaccines ...

TC: Do we know why the epidemic has restarted faster and stronger in certain places, such as the Grand Est region, Île-de-France or Hauts-de-France, even though they had already been affected? strongly?

MS: We are still working on quantitative proof (we will submit a scientific article soon on this subject) but the structure of the habitat, the density of the population, seems to play a major role. We know that in addition to health measures and collective immunity, the dynamics of the epidemic depend on various factors, without being able to estimate precisely the contribution of each of them for the moment.

One of these factors is the density of the habitat, the distribution of the population on the territory, and the connectivity of the urban fabric. On the eastern side of our country, there are many large cities that are very well connected. This is also where most of the borders are located, which are openings to the rest of Europe, where the virus also circulates. The weather also plays a role. There is a correlation between temperature, humidity and the circulation of the virus. However, in the east, the continental climate encourages people to stay at home. The situation is different in the West, with a milder oceanic climate.

The epidemiological history of the territories also influences the way in which the epidemic unfolds there: collective immunity is different from one place to another, just like the cumulative incidence of the disease, the level of vaccination, etc. The behavior of populations, depending on their perception of the risk of infection, also plays a role: if we consider that the risk is significant, we pay more attention to barrier gestures, we respect health measures more ... Finally, superpropagation events ( gatherings, etc.) also act as local accelerators, but are unpredictable.

All these questions deserve to be explored quantitatively and rigorously, bringing together specialists in the human sciences. Unfortunately, the time and the means are lacking.

TC: The immunity acquired during the previous waves, or the vaccination in progress, did not therefore protect these regions?

MS: Regarding vaccination, in February, it did not change much, since only 2% of the population had received 2 doses on average in the country. And in terms of natural immunization, we estimate it was less than 20%.

However, the collective immunity threshold to be reached in order to hope to limit the circulation of the virus is high, more than 70% if we take into account the overcontagiousness of the variants. The examples of epidemics having spread with little or no hindrance, for example on fishing boats, on the aircraft carrier Charles de Gaulle, and especially in the city of Manaus, in Brazil, are also edifying. We have reached peaks of relative cumulative incidence, close to those predicted by theory (more than 80%), and yet the epidemic continues. With a considerable amount of fatalities. Remember that Arnaud Fontanet and Simon Cauchemez had estimated that in the absence of measures, there could have been up to 450 deaths in our country.

Today, according to our models, the population's immunization rate is around 14%. Those of the Pasteur Institute are rather around 17%. In both cases, we are at less than 20%, and there are regional disparities ... In the least affected regions such as Brittany and New Aquitaine, we see that it is above all the local determinants that will influence the circulation of virus, rather than immunity, too weak.

According to the Institut Pasteur, vaccination however allows us to reduce hospitalizations by a fifth compared to a situation without vaccination coverage.

TC: During his press conference on March 18, Prime Minister Jean Castex affirmed that the fact of having ruled out at the end of January the option of generalized containment was "the right decision, because if we had had to confine then ( …) We should have imposed confinement on the country for probably three months ”. What do you think ?

MS: Of course not. As in the car, the braking distance is all the more reduced as the speed of the vehicle is low, a sanitary response applied earlier would have allowed a more rapid return to a low incidence, which is more effectively controllable by the triptych. screening / tracing / isolation, taking over from restrictive measures.

This would in fact have allowed better visibility in the medium term for the population, hospital services, the economic sector and scientists. All other things being equal, our model suggests that if the reproduction number had been reduced to its November level between January 15 and February 15, there would have been less than 1500 COVID patients in critical care units by mid-March. (instead of the 4269 listed on March 18.

While other countries took more draconian measures, France settled for a curfew. With relative success: of course, this made it possible to freeze the epidemic, but at a high level of circulation of the virus, which has resulted for weeks in several hundred daily deaths to which must be added morbidity, people who will have the sequelae of the infection, long forms of Covid ...

It should be understood that maintaining an epidemic in a stationary state requires all the more efforts as the initial incidence is high. Indeed, at constant means, the effectiveness of the screening, tracing and isolation measures provided by the city medicine, the ARS and the Health Insurance decreases when the number of transmission chains becomes too high.

TC: Regarding the measures, what is your opinion? Isn't it paradoxical to “confine” while pushing back the curfew schedule? To try to "curb the virus without locking us in"?

MS: No, it is relevant to encourage people to live outdoors, on condition, however, that barrier gestures are always respected, and that this is not a pretext to increase contacts outside the family nucleus. It should be noted that such a configuration is unprecedented, and is based even more on collective responsibility. It will again be necessary to wait two weeks before evaluating its effectiveness.

It should be noted that measures aimed at containing the epidemic are all the more effective the more they are taken early. If the goal is to achieve a low level of circulation, this can be done more quickly by putting in place strict measures, then releasing them after two weeks when you see the effects. If we wait too long and put in place insufficiently effective measures, we tire the population and run the risk of losing adherence to the measures. However, confinement that would be poorly respected would be the worst solution, because we would pay the high socio-economic cost, without touching the health benefit.

In Germany, the authorities have emphasized in their communication that we must not wait for the hospital situation to deteriorate before reacting. They have also set clear objectives, with a timetable, which makes the population adhere to them. In France, in December, an arbitrary limit of 5000 new cases per day was set, which was ultimately not respected. We still do not see the end of the tunnel in our country: today the spread of the virus is certainly slower than in October, but again exponential and does not yet allow to consider a general relaxation.

TC: What about the “race against time” towards spring and the vaccination coverage of which Prime Minister Jean Castex and Minister of Health Olivier Véran spoke?

MS: By mid-April, the slowdown in the epidemic will depend on the measures that have been announced tonight. Then, the vaccination coverage will probably be sufficient to contain the epidemic, in conjunction with the maintenance of the measures in place since the spring of 2020. However, the situation could become fragile again in certain territories in the event of a hasty relaxation of these measures.

But conversely, one may wonder why one-off releases have not yet been mentioned in certain spared territories, for example in the South-West. Territorialization and the precocity of measures should indeed be considered in both directions.

Mircea T. Sofonea, Lecturer in epidemiology and evolution of infectious diseases, MIVEGEC laboratory, University of Montpellier

This article is republished from The Conversation under Creative Commons license. Read theoriginal article.

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