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, 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, first 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 this research teach you?
Mircea Sofonea: We analyzed the proportion of variants by age group, examining 40,000 RT-PCR test results that specifically target certain sites used to determine whether a sample contains one of these three variants or 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 all 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), we observe—as was seen in England—that these new variants tend to be more prevalent among younger people: in the analyzed data, the proportion of infections caused by the variants decreased gradually 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 past 14 days, of the average number of people infected by a single infected individual. The basic reproduction number (or R0) refers to the number of people infected by a single infected individual at the start of an epidemic, in the absence of measures to control transmission and when the entire population is 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 declines; if it is greater than 1, it spreads.)
If we assume that the basic reproduction number of the original strain is 1, then that of the three variants combined ranges from 1.37 to 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 being less contagious than variant V1 (identified in England).
This means that if these variants had been the ones circulating at the start of the outbreak, 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 course 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 into a declining historical outbreak and a rising new one resolves this paradox.
This is somewhat 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 getting infected were younger. This shift toward younger age groups, linked to the relaxation of safety 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.
This is precisely the challenge of studying this pandemic: we must stick to quantitative analysis without relying on hypotheses that lack proven biological evidence—unlike what some “optimists” have done, who have bet on a decline in virulence, on a flood of false positives, or on a supposed “natural cycle of the virus.” But we must also avoid reasoning by pure analogy: at the start of the pandemic, the scientific community relied on knowledge from the 2002–2003 SARS epidemic, which led national and international observers to downplay its severity. Indeed, people infected with SARS were not contagious when symptoms first appeared; they sometimes 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 can see that it was consistent with a decline in the original strain and an increase in new variants, which were gradually becoming the driving force behind new outbreaks. Furthermore, it should be noted that fluctuations in the reproduction number were small: it remained above 0.9, meaning that the trend did not cause the incidence rate to drop rapidly; instead, it remained stuck at a high level, which was not sufficient to prevent a potential resurgence.
Today, we have returned to a pattern of rising infection rates, with a national reproduction number between 1.02 and 1.11 (calculated based on admissions to intensive care), representing a 50% increase in admissions over the past month. In and of itself, this is not explosive. However, given the already high hospital occupancy rates, the strain is quickly becoming a problem in critical care units in certain regions.
The Conversation: Furthermore, does the risk of other variants emerging increase as viral circulation rises?
MS: Exactly. But this isn’t just a national issue: resolving it would require global coordination. However, it is certainly always better to prevent new variants from emerging on our soil, hence the classification of the mutant detected in Lannion, Brittany, as a variant of interest.
This raises the question of global vaccination strategy: focusing vaccination on certain countries, as is currently the case, does not prevent the emergence of a variant elsewhere. The goal should instead be to break the chain of transmission everywhere, as each 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 hit hard?
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 living environment—specifically, population density—appears to play a major role. We know, in fact, 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 region, and the connectivity of the urban fabric. Along the eastern border of our country, there are many large, well-connected urban 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. The situation is different in the West, with its 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. Population behavior, based on their perception of infection risk, also plays a role: if people consider the risk to be high, they pay closer attention to preventive measures and are more likely to follow health guidelines… Finally, super-spreader events (gatherings, etc.) also act as local accelerators, but are unpredictable.
All of these questions deserve to be explored in a rigorous, quantitative 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 had received two doses nationwide. 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—over 70% when the increased transmissibility of the variants is taken into account. Examples of outbreaks that 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 outbreak continues. With a considerable number of deaths. Recall 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%. The Pasteur Institute’s figures are closer to 17%. 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, vaccination currently allows us to reduce hospitalizations by one-fifth compared to a scenario without vaccination coverage.
TC: During his press conference on March 18, Prime Minister Jean Castex stated that ruling out a nationwide lockdown at the end of 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 lasting probably 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; similarly, an earlier public health response would have allowed for a faster return to low case numbers, which can be more effectively controlled through the three-pronged approach of testing, contact tracing, and isolation, as a follow-up to restrictive measures.
This would indeed have provided greater clarity in the medium term for the public, hospital services, the business sector, and scientists. All else 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 by mid-March (instead of the 4,269 recorded as of March 18).
While other countries were implementing stricter measures, France settled for a curfew. With only limited success: while this did help to stabilize the epidemic, 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 long-term effects from the infection and those with long COVID…
It is important to understand that maintaining an epidemic at a stable level requires all the more effort the higher the initial incidence rate is. Indeed, given fixed resources, the effectiveness of testing, contact tracing, and isolation measures carried out by primary care providers, regional health agencies (ARS), and the national health insurance system decreases when the number of transmission chains becomes too high.
TC: What are your thoughts on the measures? Isn’t it paradoxical to impose a “lockdown” while pushing back the curfew? To try to “slow the spread of the virus without locking ourselves in”?
MS: No, it makes sense to encourage outdoor activities, provided that safety precautions are always followed and that this is not used as an excuse to increase contact outside the immediate household. It should be emphasized that this is an unprecedented situation, one that relies even more heavily on collective responsibility. We will have to wait another two weeks before assessing its effectiveness.
It is important to note that measures aimed at containing the epidemic are all the more effective when implemented early. 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 insufficiently effective, we risk wearing down the public and losing their support for the measures. However, a lockdown that is poorly enforced would be the worst-case scenario, 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 hospital situation 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 cannot see the light at the end of the tunnel 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 easing of restrictions.
TC: What should we make of the “race against time” toward spring and the vaccination coverage mentioned by Prime Minister Jean Castex and Health Minister Olivier Véran?
MS: Between now and mid-April, whether the spread of the virus slows down will depend on the measures announced tonight. After that, vaccination coverage will likely be sufficient to curb the spread of the virus, in conjunction with the continuation of the measures that have been in place since spring 2020. However, the situation could become precarious again in certain areas if these measures are lifted too hastily.
On the other hand, one might wonder why specific relaxations have 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.