Conversation with Mircea Sofonea: “Today, the virus is spreading exponentially”
What is the current status of the epidemic in our country? What should we make of the measures announced on Thursday, March 18, by Prime Minister Jean Castex? Mircea Sofonea, an associate professor of epidemiology and the evolution of infectious diseases at the University of Montpellier, provides the answers.
Mircea T. Sofonea, University of Montpellier
The Conversation: You recently examined variants V1 (from the B.1.1.7 lineage, initially detected in the United Kingdom 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 country. What did you learn from this research?
Mircea Sofonea: We analyzed the proportion of variants by age, examining 40,000 RT-PCR test results that specifically targeted certain sites used to determine whether a sample belonged to one of these three variants or to the “historical” strain that was circulating in our country before these variants were imported. These analyses were conducted on samples from the Cerba Group’s laboratory network, as well as from the Montpellier University Hospital, which allowed us to obtain data covering the entire country.
Analyses show that since February 16, these three variants have likely been responsible for more than half of the infections in most French regions. Although these RT-PCR data do not allow us to distinguish the Brazilian variant from the South African variant (since the sites targeted by the tests are identical for both variants), it is evident—as was observed in England—that these new variants tend to be more prevalent among younger people: based on the analyzed data, the proportion of infections caused by the variants gradually decreased with age, reaching a twofold difference between the ages of 5 and 80.
We were also able to calculate the effective reproduction number for the new variants, as well as for the original strain, for the months of January and February.
(Editor’s note: The reproduction number is an estimate, based on the last 14 days, of the average number of people infected by a single infected individual. The basic reproduction number (or R0) is used 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 course of an outbreak, this number changes; it is referred to as the effective or temporal reproduction number (Rt). If it is less than 1, the outbreak is declining; if it is greater than 1, it is spreading.)
If we assume that the reproduction number of the original strain is 1, then that of all three variants ranges from 1.37 to 1.64 (95% confidence interval). We are currently conducting more detailed analyses of each variant; variants V2 and V3 (identified in South Africa and Brazil, respectively) are likely less contagious than variant V1 (identified in England).
This means that if these variants had been the ones circulating at the start of the epidemic, before public health 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 impact on the dynamics of the pandemic, given that cases have plateaued in France and even declined in some countries in February?
MS: We did indeed observe a stable plateau, which can be easily explained: at that time, the original strain was more heavily impacted by the curfew measures. It was on the 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, even as more transmissible viruses were circulating, may have seemed paradoxical at first glance, but breaking down the incidence rate into a declining historical outbreak and a new, rising one resolves this paradox.
To some extent, this is reminiscent of the situation at the end of the summer, when we saw a significant rise in infections without any impact on hospital admissions: this was because the people who were getting infected were younger. This shift toward younger cases, linked to the relaxation of preventive measures among young people during the summer, created a sort of statistical illusion when looking solely 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.
That is precisely the challenge of studying this pandemic: we must stick to quantitative analysis without resorting to hypotheses that lack proven biological support—unlike what some “optimists” may have done by banking on a decline in virulence, a flood of false positives, or even a supposed “natural cycle of the virus.” But we must not rely on pure analogy either: at the start of the pandemic, the scientific community drew on knowledge from the 2002–2003 SARS epidemic, which led national and international observers to downplay its severity. In fact, people infected with SARS were not contagious when symptoms first appeared; in some cases, they did not become contagious until five days later. With SARS-CoV-2, people are contagious before symptoms develop, and there are also asymptomatic or mildly symptomatic individuals…
Looking back at the situation in February, we see that it was consistent with a decline in the original strain and an increase in new variants, which were gradually becoming the driving forces behind new outbreaks. Furthermore, it is important to note that fluctuations in the reproduction number were small: it remained above 0.9, meaning that the trend did not lead to a rapid decline in incidence, which remained stagnant at a high level and was not sufficient to prevent a potential resurgence.
Today, we have seen a resurgence in the spread of the epidemic, with a reproduction number ranging from 1.02 to 1.11 nationwide (calculated based on admissions to critical care units), representing a 50% increase in admissions over the past month. In and of itself, this isn’t a dramatic surge. However, given the already high hospital occupancy rates, the strain is quickly becoming a problem in the critical care units of certain regions.
The Conversation: Furthermore, as viral circulation increases, does the risk of other variants emerging also increase?
MS: Exactly. But this isn’t just a national issue: resolving it would require coordination on a global scale. However, it is certainly 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 interest.
This raises the question of the global vaccination strategy: concentrating vaccination efforts on certain countries, as is currently the case, does not prevent the emergence of a variant elsewhere. Rather, the goal should be to stop the epidemic everywhere, because every outbreak provides another opportunity for SARS-CoV-2 to mutate and give rise to a new strain that is more contagious or capable of evading vaccines…
TC: Do we know why the outbreak has resurfaced more quickly and more intensely in certain areas—such as the Grand Est region, Île-de-France, and Hauts-de-France—even though they had already been severely affected?
MS: We are still working on the quantitative evidence (we will be submitting a scientific paper on this topic soon), but the structure of the habitat and population density appear to play a major role. We know that, in addition to public health measures and herd immunity, the dynamics of the epidemic depend on various factors, although we are not yet able to precisely estimate the contribution of each one.
One of these factors is population density, the distribution of the population across the territory, and the connectivity of the urban fabric. Along our country’s eastern border, there are many large, well-connected metropolitan areas. This is also where most of the borders are located, serving as 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. In the east, however, the continental climate encourages people to stay home more often. 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, and so on. People’s behavior, based on their perception of infection risk, also plays a role: if they consider the risk to be high, they are more careful about preventive measures and more likely to comply with public health guidelines… Finally, superspreading events (gatherings, etc.) also act as local accelerators, but they are unpredictable.
All of these questions deserve to be explored in a quantitative and rigorous manner, with the involvement of scholars from the humanities. Unfortunately, there is a lack of time and resources.
TC: So the immunity acquired during previous waves—or the ongoing vaccination campaign—did not protect these regions?
MS: As for vaccination, by February, not much had changed, since on average only 2% of the population nationwide had received two doses. And as for natural immunity, we estimate it was less than 20%.
However, the herd immunity threshold required to limit the spread of the virus is high—more than 70 percent when the increased transmissibility of the variants is taken into account. Examples of outbreaks that have spread with little or no hindrance—for instance, on fishing boats, aboard the aircraft carrier Charles de Gaulle, and especially in the city of Manaus, Brazil—are also instructive. There, peaks in cumulative relative incidence were reached, close to those predicted by theory (over 80%), and yet the epidemic continues—with a considerable number of deaths. It is worth recalling that Arnaud Fontanet and Simon Cauchemez had estimated that, in the absence of measures, there could have been up to 450,000 deaths in our country.
Today, according to our models, the population’s immunization rate is around 14 percent. The Pasteur Institute’s figures are closer to 17 percent. In both cases, the rate is below 20%, and there are regional disparities… In less-affected regions such as Brittany and Nouvelle-Aquitaine, we see that it is primarily local factors that will influence the spread of the virus, rather than immunity, which is too low.
According to the Pasteur Institute, however, vaccination currently allows us to reduce hospitalizations by one-fifth compared to a scenario without vaccination coverage.
TC: During his March 18 press conference, Prime Minister Jean Castex stated that ruling out the option of a nationwide lockdown in late January was “the right decision, because if we had had to impose a lockdown then (…) we would have had to subject the country to a lockdown that would likely have lasted three months.” What are your thoughts on this?
MS: Of course not. Just as with a car, the lower the vehicle’s speed, the shorter the braking distance; a public health response implemented earlier would have allowed for a faster return to a low incidence rate, which can be controlled more effectively through the three-pronged approach of testing, contact tracing, and isolation, as a complement to restrictive measures.
This would, in fact, have provided greater clarity in the medium term for the public, hospital services, the business 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 fewer than 1,500 COVID patients in intensive care units by mid-March (instead of the 4,269 recorded as of March 18).
While other countries were implementing more draconian measures, France settled for a curfew. With only limited success: while it did help contain the outbreak, it did so at a high level of viral transmission, which for weeks has resulted in several hundred deaths per day—not to mention the morbidity, including people who will suffer lasting effects from the infection and those with long COVID…
It is important to understand that maintaining an epidemic at a steady state requires all the more effort the higher the initial incidence rate is. Indeed, given constant resources, the effectiveness of testing, contact tracing, and isolation measures carried out by primary care providers, the Regional Health Agencies (ARS), and the National Health Insurance system decreases when the number of transmission chains becomes too high.
TC: What is your opinion on these measures? Isn’t it paradoxical to impose a “lockdown” while pushing back the curfew time? To try to “slow the spread of the virus without locking ourselves in”?
MS: No, it makes sense to encourage outdoor activities, provided, however, that safety measures are always followed and that this is not used as an excuse to increase contact outside the immediate family. It’s important to note that this is an unprecedented situation, one that relies even more heavily on collective responsibility. We’ll have to wait another two weeks before we can assess its effectiveness.
It is important to emphasize that measures aimed at containing the epidemic are all the more effective the earlier they are implemented. If the goal is to achieve a low level of transmission, this can be achieved more quickly by implementing strict measures and then easing them after two weeks, once their effects become apparent. If we wait too long and implement measures that are not sufficiently effective, we risk wearing down the public’s patience and losing their support for the measures. A lockdown that is not strictly followed would be the worst possible solution, as we would bear the high socioeconomic cost without reaping the 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 goals, with a timeline, which has led to public support. In France, in December, an arbitrary limit of 5,000 new cases per day was set, but it was ultimately not met. We still can’t see the light at the end of the tunnel in our country: today, while the spread of the virus is certainly slower than it was in October, it is once again growing exponentially, making it impossible to consider a widespread easing of restrictions at this time.
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 spread of 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 precarious again in certain regions if these measures are lifted too hastily.
On the other hand, however, one might wonder why occasional easing of restrictions has not yet been discussed in certain regions that have been spared, such as the Southwest. The regional nature and early implementation of the measures must indeed be considered from both perspectives.
Mircea T. Sofonea, Associate Professor of Epidemiology and the Evolution of Infectious Diseases, MIVEGEC Laboratory, University of Montpellier
This article is republished from The Conversation under a Creative Commons license. Readthe original article.