The long-term reality of infectious diseases and pathogens
- #Maladies émergentes
- #Maladies vectorielles
- #COVID long
- #Résistance aux antibiotiques
Introduction
Infectious disease threats force us to see time differently. First, they remind us that microbes existed well before humans and that their temporal horizon corresponds to the sweeping timescale of life on Earth. They also show us that our biological history, immunity, vulnerabilities and adaptive capabilities have developed in the context of an ancient, continuous, inextricable relationship with the microbial world. Lastly, they force us to work at several timescales simultaneously, from the urgency of emerging diseases to the years or even decades of our immune memory, and zooming out even further to give us the historical hindsight we need to understand where we come from.
At the Institut Pasteur, this approach is rooted in our lengthy history. For more than 140 years, it has been a place where knowledge has been created, expanded, shared and transformed. This continuity is a strength that we need to preserve. It enables us to train up new generations of scientists, to develop synergies between disciplines, experimental approaches, clinical observation and surveillance, and to build a collective research memory. In our field, what we create will only last if we pass it on to the next generation.
A long-term vision is also necessary for discovery. Research cannot advance if it is merely a frantic quest for instant results. It progresses through trial and error, doubts, changes of tack, sometimes long periods of uncertainty. It takes time to ask the right questions, test a theory, check a result and make sure it can be reproduced. This constant rigor is what gives scientific knowledge its value and makes it worthy of our trust.
In a world that is moving at an ever faster pace, this approach to time may seem out of step. There is increasing pressure for speed, performance and instant visibility. Tools are changing, including with the explosion of artificial intelligence, which is opening vast new horizons. But just because things are moving faster, it should not stop us from thinking, asking questions, inventing. Major breakthroughs often happen when we take the time to explore the periphery, to step away from the beaten track and make space for new ideas.
That is why a long-term vision is not a byword for inertia; it is precisely what makes things happen. When a disease breaks out, when resistance or a new threat emerges, the only reason we can respond quickly is because patient, rigorous research has been carried out in advance, sometimes over years or even generations. When it comes to infectious disease threats, a long-term vision is not an optional extra. It is a scientific responsibility, a societal commitment to produce sound knowledge that can be shared and passed on, that can spur action and illuminate the public debate so that we can respond more effectively to the threat of infectious diseases.
Long COVID: the after-effects of an epidemic
Research conducted in recent years by several Institut Pasteur teams has revealed the mechanisms used by SARS-CoV-2, the virus responsible for COVID-19, to persist and disrupt the function of different parts of the body well beyond the acute phase of infection.
After 779 million reported cases worldwide, COVID-19 no longer graces our news feeds, but the virus responsible for it has not left the laboratory – or the bodies of some patients. Although in most cases, the virus disappears within a week or two of infection – or at the very least is no longer felt in the upper respiratory tract –, we know that it is capable of persisting for much longer, almost silently, in some parts of the body, its presence betrayed by a few stray symptoms.
A study coordinated by Michaela Müller-Trutwin's team in 2023 demonstrated that the virus can remain hidden in viral reservoirs in the lungs of some individuals for up to 18 months after infection. In 2021, Guilherme Dias de Melo, a scientist in the Lyssavirus, Epidemiology and Neuropathology Unit, revealed the mechanisms underlying anosmia, or loss of smell, and showed that some patients experience continued inflammation in the olfactory nervous system several months after infection.
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A long-term impact with multiple consequences
This phenomenon, known as "post-COVID-19 syndrome" or "long COVID," is characterized by a series of symptoms that appear within three months of initial infection and last for at least two months. According to a study conducted by Santé Publique France in 2022, 4% of adults in France suffer from long COVID, experiencing neurological, cardiac, respiratory, digestive, psychiatric or dermatological symptoms. Other international studies suggest prevalence in the region of 6 to 20%.
For those people affected, such chronic symptoms – including "brain fog," depression, impaired memory and anxiety – are by no means trivial and can soon become debilitating. More than two-thirds of patients in a cohort monitored by the Paris Public Hospital Network (AP-HP) report having had to take time off work, and fewer than 10% are in full remission 12 months after infection.
Revealed: how long COVID dysregulates brain cells
Although the symptoms are clear, the underlying mechanisms are not yet fully understood. But for scientists in the Lyssavirus, Epidemiology and Neuropathology Unit, the patterns and consequences of inflammation are becoming increasingly clear. In 2025, PhD student Anthony Coleon and his colleagues revealed viral activity in the brainstem and showed how the virus dysregulates neurons. "We first detected viral RNA of SARS-CoV-2 in the nervous system of infected animals 80 days after the acute phase of infection," explains the scientist. "We then revealed viral replication activity in tissues, suggesting that the virus is capable of infecting new cells at low levels."
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Once the culprit and the crime site had been identified, all that was left was to determine the weapon. The scientists studied the consequences of this viral RNA on brain function and observed a dysregulation of the genes associated with neuronal metabolism and activity – a phenomenon reminiscent of what we see in other neurodegenerative diseases like Parkinson's. "Infection appears to affect the production of dopamine, a neurotransmitter involved in regulating emotions and memory," says Anthony Coleon. This would explain the emergence of symptoms of depression, impaired memory and anxiety.
"Our study is the first to reveal the long-term biological impact of SARS-CoV-2 infection in animal models," adds Guilherme Dias de Melo. "We are continuing our research to understand how infection induces a loss of dopaminergic neuron function. This could have very real consequences for treating patients. The dysregulated genes that we identified represent potential targets for research on therapeutic molecules," he concludes.
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6 to 20 %
of people infected with SARS-CoV-2 are affected by long COVID
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More than 779 million
COVID-19 cases reported worldwide
Physician-scientists: a critical interface to respond to health challenges
The aim of this program, developed under the Pasteur 2030 Strategic Plan, is to strengthen the links between scientific research and clinical practice by providing training for physician-scientists, via a PhD thesis or a research internship, so that they develop expertise in both fields. The ability to work at the intersection of theory and practice is crucial in responding to increasingly complex health issues such as emerging infections, growing resistance to antibiotics, the impact of climate change on health and the rise of chronic diseases. These challenges require responses that link treatment with a thorough understanding of disease.
The program is open to medical students, physicians, pharmacists and veterinarians. The example of Kieran Toms, a PhD student in the Biology of Infection Unit, illustrates the philosophy behind the program. "Before starting my PhD, I worked as a doctor in a London hospital, where I treated several patients who had a form of tuberculosis affecting the central nervous system. That was when I developed an interest in bacterial brain infections, which led me to embark on a PhD exploring another such infection, neurolisteriosis," he explains. "Creating links between basic science and clinical practice is crucial to ensure that our lab-based research leads to real progress in the practice of human medicine."
In the 21st century, we need physicians who understand not only the needs of their patients and the biological mechanisms underlying disease, but also the research processes that can result in effective therapeutic solutions – in short, trained physicians who are connected to the landscape of scientific research.
Adult health is determined at the embryo stage
Elisa Gomez Perdiguero and her Macrophages and Endothelial Cells group are trying to unlock the secrets behind the production of certain immune cells. They are particularly focusing on how disruptions to the embryo can impact disease throughout a person's lifetime. The immune response is also thought to be determined during pregnancy, with infections or inflammations changing the programming of certain macrophages – cells involved in immune defense. Another building block in our understanding of the development of the immune system!
Antimicrobial resistance: a long-term battle
Pathogens are continually evolving and developing ways of resisting antimicrobial treatments. This phenomenon requires constant surveillance and long-term investment to understand the underlying mechanisms and develop innovative therapies.
Charting the progression of pathogens
From chikungunya to sleeping sickness, in 2025 the Institut Pasteur continued surveillance, diagnostics and vaccine innovation efforts as part of its commitment to tackling emerging diseases.
Chikungunya: status report for summer 2025
Chikungunya is appearing earlier and gaining new ground. Cases of the disease, transmitted to humans by bites from Aedes genus mosquitoes, are closely monitored every year in France. In 2025, the first cases were detected in May, earlier than usual, and in more French regions, especially the Grand Est – unprecedented territory for a virus previously only found in the Mediterranean basin.
Research carried out with the Pasteur Network institutes in French Guiana, Guadeloupe and New Caledonia, areas where Aedes mosquitoes have been circulating for many years, is particularly valuable in tackling this potentially severe disease, which can cause symptoms that last for weeks or even years in the case of joint pain.
Mapping the threat – a collective effort
The aim of the EMa-Tigre project, which stands for "Emergence of vector-borne diseases related to tiger mosquitoes," is to map the risk that arboviruses transmitted by Aedes albopictus will spread in France in a context of climate change. Laboratory research has shown that the mosquito is capable of transmitting at least 25 viruses, including dengue, West Nile, Zika and chikungunya. The project is funded by the Crédit Mutuel Alliance Fédérale Foundation and coordinated by the Arboviruses and Insect Vectors Unit at the Institut Pasteur, in conjunction with public health bodies (the French General Directorate of Health and regional health agencies), academic partners and mosquito control experts.
Sleeping sickness: stepping up surveillance
In collaboration with Lucy Glover's team at the Institut Pasteur in Paris, the team led by Brice Rotureau, Head of both the Parasitology Unit at the Institut Pasteur de Guinée and the Trypanosome Transmission Group at the Institut Pasteur in Paris, has developed a novel molecular test, known as SHERLOCK4AAT, to detect the main species of trypanosomes that infect animals, including the species that causes sleeping sickness in humans. Trypanosomes are transmitted by tsetse flies, which become infected after biting an animal carrying the pathogen. Identifying circulating species of trypanosomes is useful for several reasons: first, it benefits human health, as even though sleeping sickness now only affects 500 people each year, some parasites can stay in the body for several months or even years, hindering the goal of eliminating the disease by 2030; second, it is important for animal health, as the affected animals are mostly livestock (cattle and pigs) and their infection upsets economic conditions for farmers and their communities; and finally it serves a public health purpose, helping guide prevention policies.
Institut Pasteur on the front line of European vaccine innovation
The Institut Pasteur is a founder member of the European Vaccines Hub (EVH), launched in May 2025 by eleven leading institutions in five countries. The aim of EVH is to significantly reduce the development time of new vaccines to less than four months after identification of a pathogen by improving synergies between key players in the field. In France, the Institut Pasteur will be the coordinating institution for preclinical research activities and will work in close collaboration with partners including Inserm, ANRS-MIE, CEA and AP-HP.
History through the prism of biology
Understanding the history of pathogens, even ancient pathogens, can guide our response capabilities today.
The origins of leprosy
Countering the widespread belief that leprosy was introduced to the American continent by European settlers from 1492 onwards, a team of scientists from the Microbial Paleogenomics laboratory at the Institut Pasteur, the CNRS and Colorado State University recently discovered that a second species responsible for leprosy has actually been infecting humans for at least a thousand years. Mycobacterium lepromatosis is clearly less well known than M. leprae, the main pathogen responsible for the disease that still affects 200,000 people worldwide every year. But what it lacks in notoriety, it makes up for in perseverance. An analysis of nearly 800 archaeological samples has revealed the widespread historical presence of the pathogen in North and South America, from Canada to Argentina. This discovery significantly shifts our understanding of the history of leprosy, especially as the project also revealed new lineages, including one more than 9,000 years old that is still active.
The stealthy strategies of the plague bacillus
Despite three pandemics, the first from the 6th to the 8th century, the second – the most deadly in history – from the 14th to the early 19th century, and the last which began in the mid-19th century, we still have a lot to learn about plague. The latest finding, revealed by a team from the Institut Pasteur and McMaster University, is that a gene in the bacterium responsible for bubonic plague, Yersinia pestis, is thought to have evolved to enable it to extend the duration of pandemics. A reduction in the number of copies of the pla gene in the later stages of outbreaks extends the lifespan of infected hosts, especially rodents, enabling them to keep spreading the bacteria for longer. The plague bacillus was therefore able to persist by making itself less virulent, especially in more sparsely populated environments.