Conversation with Mircea Sofonea: "Today, the spread of the virus is exponential."
What is the current situation regarding the epidemic in our country? What should we make of the measures announced on Thursday, March 18, by Prime Minister Jean Castex? Mircea Sofonea, senior lecturer in epidemiology and infectious disease evolution at the University of Montpellier, provides some answers.
Mircea T. Sofonea, University of Montpellier
The Conversation: You recently looked at variants V1 (from lineage B.1.1.7, initially detected in the UK in September), V2 (from lineage B.1.351 detected in South Africa in October), and V3 (from lineage P.1 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, analyzing 40,000 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 that was circulating in our country before they were imported. These analyses were carried out on samples from the Cerba group's network of laboratories, as well as from Montpellier University Hospital, which enabled us to obtain information covering the entire country.
Analyses show that since February 16, these three variants are likely responsible for more than half of infections in most regions of France. Although these RT-PCR data do not allow us to distinguish between the Brazilian variant and the South African variant (because the sites targeted by the analyses are identical for both variants), we can see—as we saw in England—that these new variants tend to be more prevalent among younger people: based on the data analyzed, the proportion of infections caused by the variants gradually decreased with age, reaching a factor of two between the ages of 5 and 80.
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 and February.
(Editor's note: The reproduction number is an estimate, over the last 14 days, of the average number of individuals infected by one infected person. We refer to the basic reproduction number (or R0) at the start of an epidemic, in the absence of transmission control measures and when the population is entirely susceptible to the virus. During the epidemic, this number changes: it is referred to as the effective or temporal reproduction number (Rt). If it is less than 1, the epidemic is declining; if it is greater than 1, it is progressing.)
If we consider that the reproduction number of the original strain is 1, then that of the three variants combined is between 1.37 and 1.64 (95% confidence interval). We are currently conducting more detailed analyses of each variant, with variants V2 and V3 (identified in South Africa and Brazil, respectively) likely to be less contagious than variant V1 (identified in England).
This means that if these variants had been circulating at the start of the epidemic, before health prevention measures were put in place, their reproduction number would not have been three, like that of the original strain, but at least four.
TC: How do you respond to people who claim that these variants have no influence on the dynamics of the epidemic, given that it stagnated in France and even declined in some countries in February?
MS: We did indeed observe a stable plateau, which can be explained quite simply: at that time, the original strain was more affected 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, particularly V1, were gaining momentum. This slowdown, at a time when more transmissible viruses were circulating, may have seemed paradoxical on the surface, but breaking down the incidence between a declining historical epidemic and a growing new one resolves this paradox.
This is somewhat reminiscent of the scenario at the end of summer, when there was a significant increase in infections, but without any impact on hospital admissions: this was because the people who were infected were younger. This rejuvenation of infections, linked to the relaxation of protective measures among young people during the summer, created a kind of statistical illusion when looking only at the number of cases. However, this illusion disappeared when age groups were taken into account. We saw what happened next in October: the virus spread among the elderly and hospitalizations began to rise again.
This is the difficulty of studying this pandemic: we must stick to quantitative analysis, without invoking hypotheses that have not yet been proven biologically—unlike what some "reassurists" have done, betting on a decrease in virulence, on a plethora of false positives, or even on a supposed "natural cycle of the virus." But we must not reason by pure analogy either: at the beginning of the pandemic, the scientific community based its conclusions on knowledge of the 2002-2003 SARS epidemic, which led national and international observers to downplay its severity. This is because people infected with SARS were not contagious when symptoms first appeared, sometimes only becoming contagious five days later. With SARS-CoV-2, people are contagious before symptoms develop, and there are also people who are asymptomatic or have few symptoms...
Returning to the situation in February, we can see that it was consistent with a decline in the historical strain and an increase in new variants, which were gradually becoming the drivers of new outbreaks. Furthermore, it should be noted that the fluctuations in the reproduction number were small: it was still above 0.9, in other words, in a dynamic that did not cause the incidence to fall rapidly, which remained frozen at a high level and 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 based on critical care admissions), representing a 50% increase in admissions in one month. In itself, this is not explosive. However, in a context of already high hospital occupancy, the strain is quickly becoming problematic in critical care units in certain regions.
The Conversation: Furthermore, the more viral circulation increases, the greater the risk of other variants emerging?
MS: Exactly. But this isn't just a national issue: solving it would require global coordination. However, it is always better to prevent new variants from emerging on our soil, which is why the mutant detected in Lannion, Brittany, has been classified as a variant of concern.
This raises the question of global vaccination strategy: concentrating vaccination efforts on certain countries, as is currently the case, does not prevent variants from emerging elsewhere. The idea should rather be to break the epidemic everywhere, because each outbreak of infection is an additional opportunity for SARS-CoV-2 to mutate and generate a new strain that is more contagious or capable of evading vaccines...
TC: Do we know why the epidemic has rebounded more quickly and more strongly in certain areas, such as the Grand Est, Île-de-France, and Hauts-de-France regions, even though they had already been severely affected?
MS: We are still working on the quantitative evidence (we will be submitting a scientific article on this subject shortly), but the structure of the habitat and population density seem to play a major role. We know that, in addition to health measures and herd immunity, the dynamics of the epidemic depend on various factors, although we are not yet able to accurately estimate the contribution of each of them.
One of these factors is population density, the distribution of the population across the country, and the connectivity of the urban fabric. On the eastern side of our country, there are many large, well-connected urban areas. This is also where most of the borders are located, which are gateways to the rest of Europe, where the virus is also circulating. The weather also plays a role. There is a correlation between temperature, humidity, and the spread of the virus. However, in the east, the continental climate encourages people to stay at home. The situation is different in the west, which has a milder oceanic climate.
The epidemiological history of different regions also influences how the epidemic unfolds there: herd immunity varies from one place to another, as do the cumulative incidence of the disease, vaccination rates, etc. The behavior of populations, depending on their perception of the risk of infection, also plays a role: if the risk is considered to be high, people are more careful about protective measures and comply more with health measures. Finally, super-spreading events (gatherings, etc.) also act as local accelerators, but are unpredictable.
All these questions deserve to be explored in a quantitative and rigorous manner, with the involvement of specialists in the humanities. Unfortunately, there is a lack of time and resources.
TC: So the immunity acquired during previous waves, or the ongoing vaccination program, did not protect these regions?
MS: Regarding vaccination, in February, not much had changed, since only 2% of the population had received two doses on average in the country. And in terms of natural immunity, we estimate that it was less than 20%.
However, the herd immunity threshold that must be reached in order to limit the spread of the virus is high, at over 70% when taking into account the increased contagiousness of the variants. The examples of epidemics that 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, Brazil, are also instructive. Cumulative relative incidence rates there have reached levels close to those predicted by theory (over 80%), and yet the epidemic continues, with a considerable number of deaths. It should be remembered that Arnaud Fontanet and Simon Cauchemez estimated that without measures, there could have been up to 450,000 deaths in our country.
Today, according to our models, the immunization rate of the population is around 14%. Those from the Pasteur Institute are closer to 17%. In both cases, we are below 20%, and there are regional disparities... In the least affected regions, such as Brittany and Nouvelle-Aquitaine, we see that it is mainly local factors that influence the circulation of the virus, rather than immunity, which is too low.
According to the Pasteur Institute, vaccination currently allows us to reduce hospitalizations by one-fifth compared to a situation without vaccination coverage.
TC: At his press conference on March 18, Prime Minister Jean Castex stated that ruling out the option of a nationwide lockdown at the end of January was "the right decision, because if we had had to impose a lockdown at that time (...) we would have had to impose a lockdown on the country for probably three months." What is your opinion on this?
MS: Of course not. Just as with a car, the braking distance is shorter when the vehicle is traveling at a lower speed, an earlier health response would have allowed for a quicker return to a low incidence rate, which can be more effectively controlled by the three-pronged approach of testing, tracing, and isolation, in conjunction with restrictive measures.
This would have provided greater visibility in the medium term for the population, hospital services, the economy, 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 fewer than 1,500 COVID patients in critical care units in mid-March (instead of the 4,269 recorded on March 18).
While other countries took more drastic measures, France settled for a curfew. With limited success: while this did help to contain the epidemic, the virus continued to circulate at high levels, resulting in several hundred deaths per day for weeks, not to mention morbidity, people who will suffer long-term effects from the infection, and long COVID.
It is important to understand that keeping an epidemic in a stable state requires even greater effort when the initial incidence is high. Indeed, with constant resources, the effectiveness of screening, tracing, and isolation measures provided by community healthcare providers, regional health agencies, and the national health insurance system decreases when the number of transmission chains becomes too high.
TC: What is your opinion on the measures? Isn't it paradoxical to impose lockdown restrictions while pushing back the curfew? To try to "slow down the virus without locking ourselves down"?
MS: No, it is appropriate to encourage outdoor activities, provided that protective measures are always observed and that this is not used as an excuse to increase contact outside the family unit. It should be emphasized that this is an unprecedented situation, which relies even more on collective responsibility. We will have to wait another two weeks before we can assess its effectiveness.
It should be emphasized that measures to contain the epidemic are all the more effective when taken early. If the goal is to achieve a low level of circulation, this can be achieved more quickly by implementing strict measures and then relaxing them after two weeks when the effects are seen. If we wait too long and implement measures that are insufficiently effective, we will wear down the population and run the risk of losing support for the measures. However, a lockdown that is poorly enforced would be the worst possible solution, as we would pay a high socio-economic cost without reaping any health benefits.
In Germany, the authorities have emphasized in their communications that we must not wait until the situation in hospitals deteriorates before taking action. They have also set clear objectives with a timetable, which has won the support of the population. In France, in December, an arbitrary limit of 5,000 new cases per day was set, but this was ultimately not respected. There is still no end in sight in our country: today, the spread of the virus is certainly slower than in October, but it is once again exponential and does not yet allow for any widespread relaxation of measures.
TC: What should we make of the "race against time" toward spring and vaccination coverage mentioned by Prime Minister Jean Castex and Health Minister Olivier Véran?
MS: Between now and mid-April, the slowdown in the epidemic will depend on the measures announced this evening. After that, vaccination coverage will likely be sufficient to contain the epidemic, in conjunction with the measures that have been in place since spring 2020. However, the situation could become fragile again in certain areas if these measures are relaxed too quickly.
Conversely, however, one might wonder why occasional relaxations have not yet been mentioned in certain unaffected areas, such as the Southwest. The territorialization and early implementation of measures should indeed be considered in both directions.
Mircea T. Sofonea, Associate Professor of Epidemiology and Evolution of Infectious Diseases, MIVEGEC Laboratory, University of Montpellier
This article is republished from The Conversation under a Creative Commons license. Readthe original article.