In many ways, they will remain a backyard miracle in this global Covid-19 outbreak. Messenger RNA vaccines are being designed, tested, manufactured and brought to market at unprecedented speed. A brief chronological look back in five stages: December 2019, first cases of Sars-CoV-2 detected in Wuhan (China); at the end of January 2020, it took the Moderna company four days to produce its vaccine; in March, the first trials on humans; December 2020, start of the vaccination campaign in France; December 2022, 140 million doses delivered in France, 90% of adults vaccinated. “The crisis has made vaccination make a technological leap”, observes infectious disease expert Anne-Claude Crémieux in her book Citizens have the right to know (Fayard). Tomorrow messenger RNA vaccines could revolutionize the treatment of other infectious diseases (HIV, malaria) or even help defeat cancer. But the pandemic has also made it possible to advance medicine in many other fields…
Wastewater to better monitor microbes
Summer 2020. The “reassuring” repeat endlessly that the pandemic is over. However, a handful of virologists already know that’s not the case. “The virus, excreted in the faeces of infected people, had reappeared in wastewater at the end of June, but our alarms remained a dead letter,” recalls Vincent Maréchal, co-founder of the Obépine project (Epidemiological Observatory in Wastewater). The second wave will prove his team right, and will confirm the interest of scrutinizing the sewers to follow, or even anticipate, the evolution of the epidemic. Obépine will follow up to 200 stations.
The idea is not new: Since the 1930s, sewage treatment plants have served as watchdogs against polio. Subsequently, the wastewater will be used to monitor the consumption of antibiotics, birth control pills or medications. “But it is precisely Covid that has given a boost to this technique,” underlines Vincent Maréchal. The European Union now recommends that all Member States use this surveillance tool. In France, the project was transferred in April 2022 to the Ministries of Health and the Environment, under the name of SUM’eau. Since August, the administration has been monitoring 12 wastewater treatment plants (one in each major region except Corsica). «The system is destined to become fully operational from the end of the first quarter of 2023, with a greater number of sites», assures the Directorate General of Health.
For their part, the Obépine scientists set themselves a new challenge: to create a research platform to fight emerging infectious diseases. To do this, they will monitor common viruses in our latitudes (influenza, RSV, etc.) and build mathematical models by crossing epidemiological data and signals from wastewater treatment plants. This work will then be applied to farm monitoring (avian or swine flu), and above all to preventive monitoring in the face of new threats (dengue fever, vaccine-derived polio virus, mpox, zika, etc.). “We are also developing and validating sampling tools adapted to countries without sewage networks, because wastewater epidemiology is proving to be very effective and inexpensive,” announces Vincent Maréchal. This technique has not finished being talked about.
In intensive care, the revolution of high-flow oxygenation
Even in intensive care and intensive care units, Covid-19 has moved the ranks, with the generalization of high-flow oxygen therapy. For patients suffering from acute respiratory failure, this mode of oxygen delivery, which allows up to 100 liters of the precious gas to be delivered to the patient per minute (when low flow represents 2 to 10 liters per minute) has marked a real and its own turning point in patient care. “In intensive care it is a significant change in how we operate,” notes Professor Djillali Annane, head of the intensive care unit at the Raymond-Poincaré hospital (AP-HP) in Garches.
The breakthrough came at the onset of the Covid-19 crisis, when intensive care unit teams, faced with a shortage of ventilators, turned to these hitherto little-used oxygen dispensers. “This incidentally led to the generalization of high-flow oxygen therapy, which proved to be very effective. And today it has become routine in intensive care units,” explains Pr. Annane. By avoiding the use of invasive and dangerous intubations for the patient – in particular due to the risk of infection and positioning under general anesthesia – this method of administering oxygen has made it possible to reduce mortality in intensive care services, assures the doctor.
Since then this practice has no longer been reserved for Covid patients alone, but has also been extended to other pathologies that usually required placement in artificial ventilation. “We can really say that there was a before and an after,” Djillali Annane points out.
Sequencing of viruses, key to understanding their evolution
Until three years ago, the genetic sequencing of viruses and its analysis – which goes by the name of phylogenetics – were disciplines unknown to the general public. By now everyone has heard of the variants of Sars-CoV-2. Furthermore, many have seen the famous “family trees”, which show how the virus has mutated since the end of 2019, from the original strain of Wuhan to the Alpha, Delta variants up to Omicron and its subvariants.
And, while these disciplines remain sharp, many now know that they have helped us fight Covid. It is thanks to them that the investigation into the origin of the virus – still ongoing – is possible, that we know when and where a new variant is spreading and that researchers can offer precise models of the epidemic. “We were struck by the interest of the general public in our work and by being called upon by the media to disseminate it. This has been very motivating for our entire field”, testifies Samuel Alizon, one of the leading French experts in phylodynamics, director of researcher at the CNRS, head of the ecology and health evolution team at the Collège de France.
Genetic sequencing has been one of France’s strengths, generating numerous sequences and producing a large amount of data from PCR samples. “On the side of phylogenetic analysis we were weaker, but Great Britain, the United States or Switzerland have shown the importance of this field, adds the researcher. In France, we have however been integrated into research projects, which have allowed us to get funding… Whether this is a temporary interest or not remains to be seen.”
More efficient testing for better care
While some city doctors continue to rely on their judgment rather than a Streptotest to determine whether or not to prescribe antibiotics for angina, rapid tests appear to have a bright future. The Covid pandemic has given a strong boost to some practices: antigen tests, self-tests or multiplex PCR capable, in a few hours, of detecting multiple pathogens simultaneously, or even of identifying resistance genes.
And the future will undoubtedly give the diagnostics industry the opportunity to go even further. Because, as a recent report drawn up by the members of six academies (Medicine, Science, Technology, Agriculture, Veterinary and Pharmacy) recalls, we can expect, in addition to the appearance of new viruses, the appearance of bacterial epidemics originating due to the development of resistance to antibiotics of existing infectious agents. Their mastery will pass, for these experts, through the massive use of tests capable of detecting them to administer treatments wisely. “I hope that in the future we will move towards faster tests,” confirms Dr. Thierry Naas, bacteriologist at the Bicêtre hospital (AP-HP).
However, this power increase supposes removing some brakes. The first is industrial: currently the development of diagnostic tools depends too much on raw materials and foreign know-how. The high price of new techniques also makes their adoption more difficult. “For example, a multiplex PCR test costs around 100 euros,” confirms Thierry Naas. While a few cents are enough to cultivate a microorganism.
