Professor Philippe Sansonetti explains that a lockdown was needed because social distancing measures were not enough on their own. He goes on to outline the conditions that will be required for a future exit strategy – but makes it clear that this strategy will not signal the end of distancing measures.
The original strategy of "flattening the curve" (see, in French, chapter 1 of Philippe Sansonetti's opinion piece, "COVID-19, chronicle of an expected pandemic – Portrait of the pandemic", on the website La Vie des Idées), which aimed to relieve the strain on healthcare systems by spreading the progression of the COVID-19 outbreak over a longer period, was initially based on the introduction of social distancing. This approach, which involved remaining at a safe distance from other people, avoiding hugging, cheek kissing and shaking hands, and adopting strict hygiene measures including frequent hand washing, proved to be inadequate.
"Somehow we find it hard to believe in pestilences that crash down on our heads from a blue sky."
– Albert Camus, The Plague
There were two indications of this back in the second week in March: the exponential increase in hospitalized cases of COVID-19 and the risk that the capacities of intensive care units would be rapidly exceeded. We saw the drama unfold in Italy over the two previous weeks, and all the conditions were in place for the "Italian" scenario to be reproduced in France. At that stage there were two possible solutions: taking a gamble on herd immunity, or opting for social distancing.
Two methods to curb a disease outbreak
1/ The first method was to do nothing, as envisaged in the Netherlands and initially in the United Kingdom, and to wait for the prevalence of infection in the population to generate a sufficiently high proportion of immunized individuals, creating a "herd immunity" that would prevent the virus from circulating because it would be unable to find enough immunologically naive targets. The basic reproduction number (R0) of COVID-19 is 2.5, so the percentage of the population that would need to be infected to obtain this herd immunity and bring R0 below the epidemic threshold (R0<1) can be calculated using the equation: % infected population required = 1-1/R0, or 60%. This obviously depends on the disease generating solid protective immunity in every case, something that has not yet been formally demonstrated for this virus, which is highly effective in neutralizing the cellular immune responses needed for it to be fully eradicated in infected patients.
Read the Institut Pasteur press document: "What's herd immunity?" - "Qu'est-ce que l'immunité collective ?" (in French)
The herd immunity option was not feasible given the number of severely ill patients that the outbreak, already increasing exponentially, was set to generate in a very short space of time. It also became clear that the virus was highly contagious, in particular because of the high level of viral shedding by large numbers of asymptomatic, minimally symptomatic or pre-symptomatic carriers. The actual number of infected subjects at that time was clearly far higher than the number of biologically confirmed cases, a figure calculated almost exclusively on the basis of hospitalized patients. In short, we were blind, in the absence of even approximate epidemiological data on the real attack rate of the disease. The history of epidemics teaches us that the ability to identify all patients exhaustively, including healthy carriers, is crucial in effectively controlling the spread of a pathogen.
Read the Institut Pasteur press release: "COVID-19: modeling indicates that almost 6% of French people have been infected"
"The herd immunity option was not feasible given the number of severely ill patients that the outbreak, already increasing exponentially, was set to generate in a very short space of time."
In the late 19th and early 20th century, Europe and the United States were regularly beset by outbreaks of typhoid fever, which could reach dramatic proportions in urban environments. The source of these outbreaks often remained unknown, but Robert Koch soon identified that they were caused by the existence of chronic asymptomatic carriers of the typhoid bacillus who shed the pathogen in their stools and contaminated their environment. A well-known case was the infamous "Typhoid Mary" in New York, who worked as a cook in a restaurant and successively contaminated hundreds of individuals because she stubbornly refused to change her job. She was ultimately thrown in jail by the authorities... During the early days of the typhoid fever outbreaks, Robert Koch and his students developed a large-scale diagnostic approach, which included identifying asymptomatic carriers. Any individuals with positive stool tests were immediately placed in quarantine. This approach, requiring intensive work by health officials and diagnostic laboratories, was so well honed and effective that before his death in 1911, Robert Koch openly expressed doubts as to the need to vaccinate against the disease.
A century on, given the absence of sufficient diagnostic capabilities that would enable the identification of "contaminators", especially asymptomatic carriers, we were reduced to an extrapolation of the number of cases and carriers. Taking a minimum basis of 10 times the number of hospitalized cases, it was easy to conclude that with 10% of severe forms, hospital capacities would be overrun in a matter of days. There is a precedent: during the 1957 "Asian flu" pandemic, the UK's National Health Service was pushed to breaking point and for ten days it was unable to cope with the tide of severely ill patients, especially since its workforce was seriously depleted because of the number of staff falling ill themselves. Who said that history never repeats itself? In more recent memory, the 2002-2003 SARS outbreak showed the extent to which healthcare workers were exposed and infected. In Hong Kong, "patient zero" was a medical professor from Guangdong who had treated the first patients in his city, the early hub of the outbreak. The scenario was reproduced in Toronto, the other major secondary cluster. What was worse was that the contaminated medical staff themselves became a source of contamination. A lesson should have been learned from these dramatic episodes (and many others): the first target of an outbreak of this nature is medical staff, which is why it is vital to maintain sufficient supplies of equipment to protect against the microbiological risk.
2/ The situation in the Grand Est region in eastern France, which saw the development of a highly virulent "Italian-style" cluster, soon confirmed fears that the healthcare system and its therapeutic resources would be irreversibly overrun. By mid-March, that had led to the adoption of the second solution: stepping up social distancing by introducing more suppressive measures – the closure of schools, public places and "non-essential" shops and, over the following days, a "lockdown" of the entire population, in full knowledge of the economic and social risks involved. The fact that the first signs of a slowdown in the dynamic of the outbreak were only observed after four weeks of lockdown gives us an idea of what the scale of the catastrophe would have been if the policy had been limited to the social distancing measures applied at the beginning. During this uncertain period, the heroic efforts of healthcare workers on the front line, themselves now the main victims of the infection, deserve ample mention in our history books.
Distancing must continue after the end of the lockdown
It is now vital to analyze the potential causes of the failure of the initial social distancing measures that led to a lockdown in France, as well as in Italy, Spain and the United Kingdom, the four countries currently bearing the brunt of the pandemic in Europe, and to ask ourselves why the mortality rate in Germany was lower, although it applied a similar approach. For the only viable approach to exiting lockdown is to reapply those initial social distancing measures, once the conditions appear to be favorable for embarking on the exit process and taking all necessary steps to ensure that it is effective.
While China immediately opted to enforce a total lockdown, strictly executed by a political system with the means to do so, other Asian countries like Singapore, Taiwan and South Korea initially pursued policies to control the outbreak by the early introduction of social distancing, with populations that willingly toed the line, having suffered the trauma of emerging infectious outbreaks on several previous occasions. This approach was characterized by rigorous individual hygiene measures including the use of masks among the general population, widespread use of diagnostic tests with the aim of identifying and isolating patients and carriers of the virus, together with contact tracing methods using artificial intelligence to detect any contacts and place them in two-week quarantine. At-risk individuals were confined, especially elderly people. By using these methods, South Korea managed to control the outbreak, despite a highly virulent cluster in the south of the peninsula which seriously threatened the entire country. These countries are of course not immune to a potential second wave, since their early success in controlling the outbreak means that they are highly unlikely to have reached the rate of infection needed to develop herd immunity. In the past few days, Singapore, applauded for its exemplary handling of the outbreak after initially appearing to bring it under control, has seen a sharp rise in the number of cases and deaths, and the city-state decided to impose a total lockdown on April 7. This is a cause for major concern, and discussions with Chinese colleagues who are not afraid to speak out also revealed deep-seated fears of a second wave, after initial satisfaction with the country's impressive early success in controlling COVID-19.
Read the Institut Pasteur press document about SARS-CoV-2 diagnostic tests (in French)
"In the past few days, Singapore, applauded for its exemplary handling of the outbreak after initially appearing to bring it under control, has seen a sharp rise in the number of cases and deaths, and the city-state decided to impose a total lockdown on April 7."
It is clear that the "Asian Tigers" were keen to prioritize their economies and adopted strategies to this end. Everything will depend on their long-term viability – for nothing is certain at this stage. Entire swathes of what Charles Nicolle referred to as the "evolutionary genius of infectious diseases" are still eluding us. Perhaps the human cost that we are paying for this outbreak will result in a level of herd immunity which, while insufficient in itself, can be combined with strict social distancing measures to effectively block the circulation of the virus.
"Entire swathes of what Charles Nicolle referred to as the "evolutionary genius of infectious diseases" are still eluding us."
An objective analysis of the failure of the social distancing adopted in the early days of the crisis and the rapid accumulation of data on the disease and causative virus over the past few weeks may pave the way for the elaboration of a route out of the crisis, although we must bear in mind that it will in no way resemble a total return to normality as long as there is no vaccine. What we may hope for at this stage is that a combination of repositioned antiviral molecules will enable us to treat severe forms and reduce the viral load of patients, thereby slowing the circulation of the virus, without running the risk of resistance selection that would be raised by monotherapy. This could help bring the outbreak under the epidemic threshold more quickly. In the long term, however, drugs will not replace an effective vaccine, as we can observe for HIV, especially in low-income countries, where the cost of molecules and the need for long-term administration represent a logistical and financial burden that is difficult to sustain.
It is vital that we explain this future forecast to our fellow citizens. We need to help them understand that the current extraordinary circumstances are set to last. The end of the lockdown will not signal the end of the outbreak! The virus will still be present, albeit with less virulence than the wave we are currently experiencing, but it will take advantage of any opportunity for a resurgence. Not only does the exit strategy need to be gradual, as already announced, by geographic area and according to criteria that must be defined as soon as possible; it will also need to go hand in hand with the continuation of appropriate, enhanced, smart social distancing measures. We will come back to this. Our country, its economy, its medical staff, its movers and shakers, will not be able to cope with a potentially recurrent resurgence in cases that would require the readoption of lockdown measures on a "stop-go" basis. That is simply not feasible; we need our exit strategy to be successful, and we do not have much time to prepare for it. Its success will not only determine the extent to which society is willing to trust its political and health authorities; it will also be vital in building confidence among major banking institutions, which are currently still lending to the French government at a zero interest rate to encourage the rapid rebuilding of our economy. They will soon lose patience if we do not demonstrate exemplary discipline and intelligence. Once again, our fate is in our hands...
Reasons for the failure of the initial strategy
It is worth reflecting on the possible reasons for the failure of the initial social distancing strategy in France, since the efficacy of this very strategy will be vital for the success of our exit from lockdown.
1 – The people of France did not feel that they were at risk from the outbreak soon enough, despite the images that they were seeing from China, then Italy. This was particularly the case for young adults, who were slow to get behind any strict preventive measures because of the initial widely held belief that only over-65s were affected. The "pandemic of the century" announced in 2009 with the emergence of the A(H1N1) influenza strain elicited an unprecedented early response from national and international health services. But the outbreak ultimately confounded forecasts when it proved to be relatively mild. This remained in the public consciousness, discouraging us from taking similar outbreaks seriously and chipping away at our confidence in scientific, medical and political authorities – despite the fact that they had successfully fulfilled their role, albeit with a few hiccups along the way.
2 – Our diagnostic capabilities were not commensurate with the scale and swift progression of the outbreak: there were insufficient molecular tests (q-RT-PCR) available and we were unable to deal with the initial complexity of samples and the technical implementation of the tests. This lack of capacity prevented us from developing a proactive, large-scale diagnostic approach, especially in the most affected areas, at the crucial moment when the outbreak was gaining pace. Unaware of the real number of cases – lacking even an approximation of this figure –, we were unable to enforce systematic isolation of contagious individuals and two-week quarantines of their immediate contacts, let alone isolation measures at an even earlier stage. This paved the way for the exponential spread of a virus whose R0 is higher than that of seasonal influenza.
The countries that applied widespread testing, like Korea, Taiwan, Singapore and even Germany, currently have less devastating figures, especially in terms of the absolute number of deaths. Admittedly there is a big leap from correlation to causality, and there are several potential confounding factors, but we need only remember the example of Robert Koch and the use of routine screening of asymptomatic carriers as a means of controlling typhoid fever outbreaks.
3 – Individual hygiene measures were insufficient, as seen with the unavailability of masks. In view of this shortage, the official line, which aimed to persuade the population that, given a woefully inadequate supply, these masks must be used sparingly and kept for healthcare professionals, was logical and laudable. But in view of the active circulation of the virus and the awareness that it is spread by airborne droplets, why was the use of masks by the general population discredited? Why were assurances given that they served no purpose or that experts were divided on the subject? This strategy left our Asian colleagues dumbfounded. Why were people not encouraged to produce their own masks, however imperfect? Official websites could even have addressed the subject, providing guidelines and instructions for use. Homemade masks may be imperfect, but they would have helped raise further awareness among the public, as long as it was clearly explained that masks were an additional measure and that other hygiene measures were still needed. During an outbreak, any measure that might help slow the circulation of the pathogen and reduce viral shedding and contamination is welcome, even if the methods used only offer 99% protection. It is by combining several measures that we will be able to bring the circulation of the virus back under the epidemic threshold.
What conditions are needed to begin easing lockdown measures?
When should we begin lifting restrictions? The earlier the better, of course – the mental health of the population and the chances of economic recovery depend on it. There is no way we can wait for drugs and a vaccine. But we must not confuse speed with undue haste.
Two conditions are vital; they are a question of common sense as much as science:
- Have we unequivocally overcome the peak of the outbreak? No! Even though we are currently seeing signs that we would like to think of as positive, like a stabilization in the numbers of new patients admitted to hospital and requiring intensive care, the situation remains uncertain. There is still a huge strain on healthcare workers and hospital capacities, despite four weeks of lockdown, and we are beginning to witness a sense of fatigue in complying with restrictive measures.
- Do we currently have all the ingredients we need to give the exit strategy every chance of success? No! And there is still much that needs to be done, even as the clock is ticking.
We need to clearly explain to the French population that deciding on the date when the lockdown will begin to be lifted is not a matter of sticking a pin in a calendar. It will depend on objective criteria, on data that show the status of the outbreak region by region – and that in turn requires the availability of molecular and serological diagnostic tools to carry out this research. It will also depend on the availability of personal protective equipment to safeguard the "liberated" population against the ongoing circulation of the virus. All this can of course be modeled, with scenarios ranging from optimistic to pessimistic, but we need to have the courage to admit to our fellow citizens that while our modeling experts are extremely talented, and while mathematical techniques based on sophisticated algorithms are highly valuable, there are still gray areas in our biological understanding of the interaction between SARS-CoV-2 and humans that make predictions difficult. This was evident in the period before the lockdown. There are some key questions that currently remain unresolved, even if over time (but how much time do we have?) some points are becoming clearer.
"We need to clearly explain to the French population that deciding on the date when the lockdown will begin to be lifted is not a matter of sticking a pin in a calendar. It will depend on objective criteria, on data that show the status of the outbreak region by region – and that in turn requires the availability of molecular and serological diagnostic tools to carry out this research."
Although it is becoming clear that infected individuals shed a high viral load from the very beginning of the illness, even at an asymptomatic or minimally symptomatic stage – and in many patients the illness will not develop any further –, data on the duration of viral shedding after clinical recovery are rare, and those that do exist are not reassuring. Are cured patients naturally protected against infection, whether or not they have developed the specific neutralizing antibodies that we are hearing so much about and for which we hold out such hope? And more to the point, are individuals who remained asymptomatic or minimally symptomatic protected, and for how long? In these individuals, the virus will have been confined to the nasopharyngeal mucosa, so there may be local immunity, but for how long? What level of protective efficacy does it offer? Can it ultimately lead to effective systemic immunity? In short, will the herd immunity generated by other infectious diseases or by vaccines fulfill the same functions for SARS-CoV-2? This information is vital if we are to look to the future and avoid resorting to "short-termism." The virus is cunning, and we need to respond by investing time and money in high-level clinical and basic research to shed light on its many unresolved yet crucial aspects.
Finally, it is worth attempting to summarize the conditions in which lockdown restrictions might be eased in such a way that raises the least possible chance of a local or more widespread resurgence of the outbreak.
1 - A region-by-region exit strategy could be envisaged, as long as the available epidemiological data indicate that the wave of infection has come to an end in regions that witnessed highly active clusters (Grand Est, Greater Paris, etc.) and that the attack rate has not increased over a period of several weeks in regions that were relatively spared by the outbreak. These assessments will of course be based on data from hospitals and family physicians, confirming a significant easing of the strain on the healthcare system. They will also require the rapid organization of large-scale, methodologically sound serological testing, with the aim of evaluating the overall attack rate, in other words the percentage of the population that has been infected by SARS-CoV-2, based on the presence of specific antibodies.
Read the Institut Pasteur press document : "Covid-19: mathematical model indicates that between 3% and 7% of french people have been infected"
Furthermore, it seems only logical to factor in additional data on epidemiological impact obtained by widespread molecular diagnostic testing with q-RT-PCR, the technique used to identify clinical cases. We will come back to this.
We also need to seriously consider the consequences of a total exit from lockdown if it includes people at high risk of developing severe forms, such as individuals above the age of 65, immunosuppressed individuals and diabetic and severely overweight individuals. There is no room for political correctness when it comes to protecting the lives of our fellow citizens.
2 - Once the exit strategy has been decided, it must go hand in hand with a program of molecular testing that covers as much of the population as possible, with the aim of detecting the presence of the virus among symptomatic, minimally symptomatic and asymptomatic subjects, not only in hospitals and retirement homes but among the general population, with a particular emphasis on populations, professions and areas at risk. Any positive individuals can then be isolated in conditions that are yet to be determined and organized, since the issue is incredibly complex in human and logistical terms. The implementation of widespread testing will be just as complex – the logistics of large-scale sampling, transporting samples, technical practicalities, how to report results and how to proceed once it has been decided that an individual should be placed in isolation.
This approach also needs to be combined with a strategy to trace the contacts of infected patients. The practice of contact tracing is already a source of controversy – understandably, since it immediately suggests a further erosion of our civil liberties, which have already been somewhat undermined by antiterrorism laws. We need to address this issue as soon as possible and emphasize just what an extraordinary aid these technologies can represent in our efforts to detect the disease and impose a two-week quarantine on anyone in close and/or repeated contact with individuals that have tested positive. Artificial intelligence, machine learning, big data – all these approaches can be combined with more conventional methods to produce the solid epidemiological basis that will be needed to prevent a resurgence of the virus once we exit lockdown. It goes without saying that if this unprecedented strategy is chosen, it must be governed by a strict legal and ethical framework, and the maze of complex logistical issues and multidisciplinary methodological dimensions must be navigated by experienced scientists with a strong moral compass. The strategy will also have to be supported by citizens, rather than imposed on them, via a concerted and transparent effort to inform and encourage active participation. Lockdown, the call to "stay at home!" to save lives and protect our healthcare workers, is vital, but it creates an incongruous social reality where our horizons are limited to hospitals, supermarket queues and police checks of self-declaration forms. The public needs to be able to move beyond the confines of this narrow perspective and gear up to play an active role when the lockdown is eased. We need this "third line" to step up to the plate now, in readiness for exiting lockdown. Representatives of health authorities and police officers cannot realistically be expected to do everything – instead, trained volunteers should be in a position to shoulder organizational responsibilities for implementing the exit strategy in apartment buildings, local districts, residential areas and public transport. Maybe COVID-19 will help us reconnect with the foundations of our democracy and rekindle our republican spirit? Charles Nicolle wrote that "infectious diseases teach men that they are brothers in solidarity." After witnessing the extraordinary reserve of our healthcare system in its broadest possible sense, we now need to make way for a "civic reserve." And there is also a third "reserve" that will be vital, namely "scientific reserve." In addition to the minority working in our research centers on COVID-19, hundreds – thousands – of scientists capable of designing, innovating and producing sophisticated tests are chomping at the bit, frustrated that they have thus far been unable to contribute to the fight. They are often the first to join the ranks of volunteers, and there is ample evidence of their extraordinary generosity. Some, despite the dangers involved, put their research projects or PhDs on hold so that they could travel to Guinea in 2015 as volunteers to support the diagnostic laboratory set up by the Institut Pasteur on the front line of the Ebola outbreak. On the front line of COVID-19 in Italy, several of our colleagues promptly converted their laboratories into diagnostic centers. We need to make room for scientists in the future strategy. If "we are at war," then let us wage this war seriously; let us put administrative barriers, regulations and accreditations to one side for the time being and harness our "scientific reserve."
3 - Once the exit strategy has been decided, it must go hand in hand with a strict continuation of social distancing and individual and collective hygiene measures, including the use of masks, either "professional," if available, or "homemade." Lockdown will be impossible as long as there continues to be a chronic shortage of stocks of masks and hand sanitizer in pharmacies. As proposed above, "civic reserve" could play a key role in this context by informing, assisting and supporting people, in the street, in places where there may be gatherings, in public transport – a potentially propitious environment for a resurgence in contamination when people go back to work.
4 - Travel between regions must remain limited to professional imperatives, with the exception of some scenarios to be defined.
5 - Gatherings must remain prohibited, with some exceptions, but in extremely limited forms such as funerals. Some sports events and religious gatherings unfortunately seem to have played an important role in creating active clusters for the spread of the virus in Italy, Spain and France. Companies must make careful and effective provision for social distancing. For businesses that are frequented by people – shops, restaurants and hotels, a key pillar of our economic and social life – we urgently need to find solutions, however restrictive and difficult they may be to implement. Some have already been tested in shops selling essential items. When it comes to entertainment – plays, shows, concerts – and schools, we should already be looking ahead to September.
Only when we begin to have a reliable map of the evolution of the outbreak after lockdown, when R0 is at a stable level below 1 (below the epidemic threshold, indicating that there is no likelihood of a new wave), can we start to ease the pressure of the measures outlined above – sensibly, rationally, progressively, since it is clear that restarting the economy, restarting life in general, will require sustained support to ensure that the cure does not prove worse than the disease.
How long? As long as it takes, we may be tempted to say. But can we be more precise?
We must have the humility to say that we do not really know at this stage, that part of the "evolutionary genius" of the disease still eludes us and that SARS-CoV-2 may change its behavior – for better or worse – in the blink of an eye if it undergoes a mutation. Models even suggest that the current lockdown may merely be paving the way for a resurgence of the outbreak after the summer... But the timeframe for exiting lockdown will primarily depend on how well we comply with the measures taken.
If we had to give a figure, let's say at the very best sometime over the summer – unless an effective treatment emerges soon. Ongoing clinical trials will give us a clearer idea of this in the coming weeks. The widespread availability of a treatment would instantly mitigate what is so alarming about this disease, namely its severe or even fatal forms, and reduce the overall viral load in circulation, making a significant and potentially decisive contribution to keeping R0 under the epidemic threshold.
In any case, enhanced social distancing and hygiene measures will have to be kept in place as long as there is no vaccine – which may be the case for several months and in all likelihood a year. We will get used to it. The human race is resilient.
To close, a personal note of hope, one of sadness and one of concern
First, hope and confidence: science will offer solutions to this crisis that is paralyzing our country, our continent and our planet. Biomedical, basic, academic and industrial research – all possible forces are being mobilized and considerable investments are being made with the aim of discovering, testing, developing and approving therapeutic molecules and vaccines.
Sadness for the European dream. Europe has failed the COVID-19 test. It failed its entrance examination at the beginning of the crisis, with no coordination and nationalist tendencies that were unfortunately all too predictable. These expressions of national self-interest will leave a deep and lasting scar for those European countries worst affected. Europe also seems to be well on the way to failing its final examination. Despite the need for integrated management of the health-related, scientific, economic and social aspects of exiting lockdown, it appears that this key moment for European citizens – a moment that in itself holds the sum total of all dangers and all hopes – is also destined to be shaped by national self-interest. What will the billions of euros pledged by the ECB be worth without a smart, collective European approach rooted in solidarity? The worst-case scenario is not set in stone; a miracle is always possible. But what will become of the European Union after the crisis?
Finally, a note of concern. Would this overwhelming scientific, medical, social and economic reaction to the pandemic have occurred if COVID-19 had not first affected wealthy countries? The pandemic is developing slowly but surely on the African continent and in other poor regions of the planet. Let us do all we can, now, to make sure that the southern hemisphere can benefit equally from any therapeutic resources and vaccines that are developed. "Brothers in solidarity..." – let us heed the words of Charles Nicolle.
"Let us do all we can, now, to make sure that the southern hemisphere can benefit equally from any therapeutic resources and vaccines that are developed."
This study is part of the priority scientific area Emerging infectious diseases of the Institut Pasteur's strategic plan for 2019-2023.
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