For diabetic patients confined during the Covid 19-epidemic, the AP-HP, in partnership with Inserm and University of Paris, launches CoviDIAB, a national application for information, prevention and support online

©Dimitri Karastelev on Unsplash

The AP-HP, the Federation of Diabetological Hospital Services (Bichat Hospital, Professor Roussel, Cochin Hospital, Prof. Larger, Lariboisière Hospital, Professor Gautier) and the AP-HP Connected Health Responsibility Centre (Dr Boris Hansel Pr Patrick Nataf) offer this week to diabetic patients confined at home during this period of Covid-19 outbreak a national programme of information, prevention and support for their health.

“Diabetes is one of the situations at risk of severe COVID-19 infection,” recalls Professor Ronan Roussel, diabetologist at the Bichat Hospital. “According to preliminary Chinese studies, it multiplies by 2 to 4 the risk of death due to this infection and patients with diabetes are likely to question their personal risk.” To meet this expectation, the Federation of diabetology proposes, at national level, concrete assistance based on e-health.

“We have identified three immediate needs: informing in real time, answering practical questions and directing diabetic patients to appropriate care in case of symptoms” said Dr. Boris Hansel, co-director of the Connected Health Responsibility Centre at Bichat hospital.

A collaborative initiative of teams of the AP-HP, Inserm and University of Paris.

The application is based on the IRIADE platform. Diabetic patients can register themselves or through a doctor on the website

Therefore, the diabetic patient accesses a media library updated daily. Notifications are sent every time an information useful for diabetic patients is published. In addition, through questionnaires, personalized advice are provided. Finally, questions on health status are regularly asked to refer the patient to specific treatments according to updated recommendations (GP, EMS, ER) if necessary by promoting teleconsultation. The system provides for physicians who wish it the supervision of individual alerts allowing them to work directly with their patients.

LIVE video sessions are offered to Covidiab registrants with diabetologists, hygienists and infectiologists.

The application is intended for all diabetic patients residing in France (mainland and overseas).

“The project involves teams  INSERM U1148 (LVTS connected health director Didier Letourneur)  and U1138 (IMMEDIAB, Director: Nicolas Venteclef) , AP-HP Research Foundation  and University of Paris. 

This project has also received the support of the Youtube channel PuMS: 

Deploying Cellphone Data to Fight COVID-19

©Oleg Magni on Unsplash

Inserm has joined forces with telecommunications company Orange to study the impact of confinement on population mobility and explore how using aggregated cellphone data could improve COVID-19 pandemic predictions.

Aggregated data from our cellphones could prove to be an effective tool in fighting the spread of coronavirus. A collaboration between Inserm and Orange will enable this data to be used for specific research purposes in a pandemic context, in order to improve our understanding of the impact of confinement and the spread of the virus.

Leading the project is Inserm researcher Vittoria Colizza, who has already been working with Orange for several years in order to study the links between population mobility and the spread of various diseases, particularly in Africa. This new study will be based on the use of aggregated and anonymized mobility data provided by the operator. Under no circumstances is the intention to study individual personal data or track individual movements. 

“We will not be looking at the movements of any particular individuals, at how they move or where. Our focus will be on analyzing anonymized quantitative data that describe mobility between geographical areas thanks to the localization of relay masts that manage communication signals (calls, text messages). These indicate the number of movements made from one area to another in France”, explains Inserm researcher Eugenio Valdano, who is working on the project with Colizza.

The team will nevertheless be able to have access to these data compiled according to age group, which will give them a more precise idea of the demographic profile of those moving between geographical areas.

Mobility and pandemic spread

The data provided by Orange will be used in two ways in this study. First, Colizza and her colleagues will analyze mobility before and after confinement, looking at the spontaneous changes in mobility which appeared even before confinement began. The objective is to have a better idea of how people themselves change their behaviors in response to an epidemic. In addition, studying the mobility data recorded since confinement began will enable a better understanding of its impact on the course of the epidemic and to evaluate how it is respected by the population.

Secondly, the data will be integrated into models of epidemic spread developed by the team, in order to better predict how the virus will spread by taking into account mobility but also to identify the regions at risk of becoming clusters and to model the impact on the healthcare system. “The availability of such data is very important in order to better advise public decision-makers on how to allocate healthcare resources and to inform them of the most vulnerable regions”, emphasizes Valdano.

While such research can usually take several months, the initial results of this study are expected in the weeks to come, given the urgency related to the rapid progression of the pandemic.

Exploring the Brain to Clarify the Link Between Sleep Disorders and Alzheimer’s Disease

©Adobe Stock

Sleep disorders have a harmful impact on our brain and under certain conditions are thought to be linked to an increased risk of Alzheimer’s disease. A link which had until now been poorly understood by the scientific community. For the first time, a study based on multiple brain imaging techniques conducted by Inserm researcher Géraldine Rauchs at two laboratories hosted at GIP CYCERON – the Physiopathology and Imaging of Neurological Disorders laboratory (Inserm/ Université de Caen-Normandie) and the Neuropsychology and Imaging of Human Memory laboratory (Inserm/Université de Caen-Normandie/Ecole Pratique des Hautes Etudes – PSL/CHU Caen) – has revealed, among other forms of impairment, the appearance of amyloid plaques characteristic of Alzheimer’s disease in the brains of older adults with sleep apnea but no cognitive disorders. The results of this research were published in JAMA Neurology on March 23, 2020.

Obstructive sleep apnea syndrome is the most common sleep breathing disorder, affecting more than 30% of the population over the age of 65. It consists of uncontrolled and repeated pauses in breathing during sleep, linked to the temporary obstruction of the upper airways, in the throat, and is linked to numerous health problems – primarily cardiovascular diseases. However, given that the condition remains silent for a long time, it is probably underestimated in the general population.

In recent years, there has also been an accumulation of scientific data showing a link between sleep quality – and particularly the presence of sleep apnea – and the development of Alzheimer’s disease. Nevertheless, the biological mechanisms behind this link remained to be elucidated.

In order to do this, Inserm researcher Géraldine Rauchs conducted a study at the Physiopathology and Imaging of Neurological Disorders[1] laboratory (Inserm/ Université de Caen-Normandie) in collaboration with the Neuropsychology and Imaging of Human Memory laboratory (Inserm/Université de Caen-Normandie/Ecole Pratique des Hautes Etudes – PSL). This study[2], published in JAMA Neurology, used a variety of brain imaging techniques to map cerebral changes in people with untreated sleep apnea, on the structural, molecular and functional levels.

Changes in the brain

The researchers began by recruiting 127 participants over the age of 65, in good health and with no cognitive disorders. Using a portable home device to record their sleep and breathing overnight, the researchers detected the presence of varying degrees of sleep apnea in 75% of them.

In addition, the participants all underwent a battery of tests to evaluate their cognitive function, particularly executive functions and memory. They answered questionnaires about how they perceived their cognitive function and sleep quality. Several brain imaging examinations were then conducted in order to study their brain from every angle and detect any changes potentially linked to Alzheimer’s disease. Although no differences were observed among the participants in terms of cognitive performance, the imaging did reveal several notable changes in the brains of those with sleep apnea.

In these participants, there is a more marked accumulation of beta-amyloid protein in the brain. Characteristic of Alzheimer’s disease, this protein accumulates in the form of plaque which, depending on its density and distribution in the brain, may lead to the onset of clinical signs of the disease. Furthermore, the researchers observed increases in gray matter mass and glucose consumption, suggesting the presence of inflammatory processes in the brain.

“At a time when clinical trials of Alzheimer’s treatments are not yet successful, identifying risk factors and protection factors to target is of interest to a growing number of researchers. Thanks to the use of multiple brain imaging methods, this study has enabled us to clarify the mechanisms explaining the links between sleep quality, risk of cognitive decline and Alzheimer’s disease”, explains Rauchs.

While this does not mean that these people will necessarily develop the disease, they are at higher risk. What is more, effective solutions exist to treat sleep apnea. Detecting and treating sleep disorders, particularly sleep apnea, will therefore form part of the arsenal for promoting successful aging.

To continue this research, Rauchs and her team will now look at the impact of treating apnea on changes in brain lesions and analyze the differences between the brains of male and female sleep apnea patients.


[1] PhIND laboratory:

[2] This study was conducted as part of a vast European project, the Silver Santé Study (, led by Dr. Gael Chételat.

Launch of a European clinical trial against COVID-19

A European clinical trial to evaluate four experimental treatments for COVID-19 starts today. Coordinated by Inserm as part of the Reacting consortium, this trial will include at least 800 French patients with severe forms of COVID-19.

A clinical trial, called Discovery and coordinated by Inserm as part of the Reacting consortium, starts today in France to test four experimental treatments against COVID-19. This is a European project, the French part of which is financed by the Ministries of Higher Education, Research and Innovation (MESRI) and Health and Solidarity (MSS). The European part is supported at least by COMBACTE, PREPARE and RECOVER. It is led by Florence Ader, infectiologist in the Infectious and Tropical Diseases Department of the Croix-Rousse Hospital of Lyon University Hospital and researcher at the CIRI International Research Centre in Infectiology (Inserm/CNRS / Claude Bernard University Lyon 1).

The objective is to evaluate the efficacy and safety of four experimental therapeutic strategies which, in light of latest scientific information, might be effective against COVID-19.

“We analysed data from the scientific literature on SARS and MERS coronaviruses and the first publications on SARS-COV2 from China in order to come up with a list of antiviral molecules to be tested: remdesivir, lopinavir and ritonavir in combination, the latter being administered with or without interferon beta and hydroxychloroquine. The list of these potential drugs is also based on the subset of experimental treatments classified as top priorities by the World Health Organization (WHO).

The great strength of this trial is its “adaptive” nature. This means that ineffective experimental treatments can very quickly be dropped and replaced by other molecules that emerge from research efforts. We will therefore be able to make changes in real time, in line with the most recent scientific data, in order to find the best treatment for our patients,” explains Florence Ader.

It is planned to include 3200 European patients from Belgium, France, Germany Luxembourg, the Netherlands, Spain, Sweden, and the United Kingdom. In France, at least 800 hospitalized COVID-19 patients will be recruited in conventional medicine departments or in intensive care. “Five French hospitals will initially participate (Paris – Hôpital Bichat-AP-HP, Lille, Nantes, Strasbourg, Lyon) and then we will open other centres to reach at least 20 participating establishments. Our strategy of opening centres will follow the epidemiological situation of the epidemic with a priority for opening new sites in hospitals under high pressure”. Recruitment  starts today.

“This trial is designed to be pragmatic and adaptive. Its aim is to analyze the efficacy and safety of treatment options for patients within a limited time frame. It is a resolutely proactive approach to develop tools against the disease,” she concludes.

This trial will also complement the data that will be collected as part of another international clinical trial that will soon begin under the auspices of the World Health Organization, called Solidarity.  

For more information:

The DISCOVERY trial includes five treatment modalities:

  • standard of care
  • standard of care plus remdesivir
  • standard of care plus lopinavir and ritonavir,
  • standard of care plus lopinavir, ritonavir and interferon beta
  • standard of care plus hydroxy-chloroquine.

Allocation of patients to the various treatment modalities will be randomized, i.e. by random draw, but patients and physicians will know which treatment is used (this is called an open trial). The analysis of treatment efficacy and safety will be evaluated 15 days after inclusion of each patient.

A Mushroom to the Rescue of Patients with Rare Genetic Diseases

The Lepista inversa fungus has restorative properties to correct certain genetic mutations. © Christine Bailly

An ordinary edible mushroom could be a game-changer when it comes to the treatment of rare genetic diseases. These affect hundreds of millions of people worldwide who often find themselves powerless in the absence of effective therapy. A team led by Fabrice Lejeune, Inserm researcher at the CANcer Heterogeneity, Plasticity and Resistance to THERapies laboratory (Inserm/ CNRS/ Université de Lille/Institut Pasteur de Lille/Lille University Hospital), in collaboration with a team from the French National Museum of Natural History, has shown that an active ingredient contained in the Lepista inversa mushroom has repair properties, making it possible to correct certain genetic mutations, known as “nonsense” mutations. Their findings have been published in Nature Communications[1].

Rare diseases constitute a major public health problem, affecting 300 million people worldwide. Of genetic origin in 80% of cases, there is currently no curative treatment for these hereditary conditions which include cystic fibrosis, hemophilia, and Duchenne muscular dystrophy. However, it has now been established that specific genetic mutations, known as “nonsense” mutations, are implicated in almost 10% of cases of rare genetic diseases.

DNA is made up of nucleotides, organic compounds that code the amino acids implicated in the synthesis of the proteins needed for the body to function correctly. In practice, “nonsense” mutations introduce a “stop codon” in the mutated gene – a sequence of nucleotides that brings the synthesis of the corresponding protein to a premature halt. From that point, the protein is no longer available as such, leading to the onset of the clinical symptoms of the disease.

Identifying how to correct these mutations therefore represents a major challenge for rare genetic disease researchers such as Fabrice Lejeune and his team at the CANcer Heterogeneity, Plasticity and Resistance to THERapies laboratory (Inserm/ CNRS/ Université de Lille/Institut Pasteur de Lille/Lille University Hospital), working in collaboration with the Chemical library / Extract library and JRU 7245 CNRS Communication Molecules and Adaptation of Micro-organisms of the National Museum of Natural History in Paris.

In 2017, the latter had already made a surprising discovery by showing that extracts from the ordinary edible mushroom Lepista inversa could repair nonsense mutations in three cell lines isolated from patients with cystic fibrosis.

Repair properties

In their new study, published in Nature Communications, the research teams have for the first time identified the active substance in the mushroom that is capable of correcting the nonsense mutations associated with the UGA stop codon, the most common of the three stop codons of the human genetic code.

By fractionating extracts of the Lepista inversa mushroom, the researchers were able to identify one of its active substances – compound DAP (2,6 diaminopurine). They showed that this compound repairs nonsense mutations in human cell lines, and also in animal models. It is also of very low toxicity.

This discovery opens up interesting therapeutic avenues for patients with rare genetic diseases. “The idea is to be able to correct the clinical aspects by repairing the nonsense mutations linked to the UGA codon and by restoring the function of the mutated gene. It must be noted that it is not about giving the mushroom to patients to consume directly, given that it contains other compounds whose effects we cannot control, but rather about developing treatments based on the active substance identified here”, emphasizes Lejeune.

The next step for the researchers will involve testing this active substance in other animal models in order to then be able to rapidly launch clinical trials should the results remain promising.


[1] A patent was filed for the discovery via SATT Lutech: Purine derivative for use in the treatment or prevention of diseases caused by a nonsense mutation – October 2017 – S. Rebuffat, S. Amand, C. Maulay-Bailly and F. Lejeune -PCT/EP2017/076846; WO2018073413A1

COVID-19: Tackling the Epidemic in 20 Research Projects

©MESRI/XR Pictures

At a time when the Sars-CoV-2 epidemic is continuing to spread, France’s Alliance for Life Sciences and Health (Aviesan) is mobilizing to accelerate research into the virus and COVID-19 disease through REACTing – a consortium coordinated by Inserm. With the support of the Ministry of Solidarity and Health and the Ministry of Higher Education, Research and Innovation, the Scientific Advisory Board of REACTing has selected 20 scientific initiatives covering diverse fields, from mathematical modelling to disease prevention and treatment.

Since the emergence of the first cases at the end of 2019, implementing high quality research to contain Sars-CoV-2 as quickly as possible and improve the treatment of those infected have been the objectives of the French scientific community, under the egis of Aviesan and the REACTing network.

Aviesan is comprised of nine essential academic stakeholders, its founding members: France’s Atomic Energy Commission (CEA), National Center for Scientific Research (CNRS), National Research Institute for Agriculture, Food and the Environment (INRAE), Institute for Research in Computer Science and Automation (INRIA), National Institute of Health and Medical Research (Inserm), Institut Pasteur, Research Institute for Development (IRD), Association of University Presidents (CPU), and Association of CEOs of Teaching and Regional Hospitals. The REACTing consortium is coordinated by Inserm.

Following a call for applications made to research teams across France, the Scientific Advisory Board of REACTing – a veritable research acceleration consortium – has selected 20 projects from a variety of scientific disciplines. Chosen for their effective and exhaustive contributions to knowledge production and to fighting this new epidemic, these projects have been categorized as follows:

  • Diagnostic, clinical and therapeutic research projects
  • Epidemiology research projects
  • Fundamental research projects
  • Human and social science research projects

Diagnostic, clinical and therapeutic research projects

In terms of therapeutic research, the projects selected concern the repurposing of existing medicines used in other diseases and the study of neutralizing monoclonal antibodies.

A clinical trial sponsored by Inserm will be set up in order to evaluate and compare four therapeutic combinations: remdesivir, lopinavir, the lopinavir+interferon combination, each combined with standard of care (non-specific and symptomatic treatments), and finally standard of care alone. A total of 3200 people will be enrolled, 800 of whom in France. This is an “adaptive” clinical trial in which ineffective compounds will be abandoned and any that appear to be useful will be tested.

Finally, one of the selected projects will analyze the accessibility of assisted ventilation protective masks and their integration in the healthcare offering.

Epidemiology research projects

Three of the selected projects concern epidemiology and modelling of the epidemic in order to better anticipate the spread of the virus by geographical area. One of the projects involves setting up an observational cohort sponsored by Inserm. Comprising all infected patients in France, this cohort will form the scientific basis for future studies.

Fundamental research projects

Three projects have been selected in the field of fundamental research, notably to further understanding of the in vitro viral replication context.

A research group will look at the animal reservoir issue, with a study evaluating the risks of virus transmission in the Mekong Delta region.

Human and social science research projects

The human and social sciences, which shed their own unique light on the epidemic and enable deeper understanding of the response of the public authorities and society as a whole, are also given pride of place. The leaders of these projects will look at the confinement of those repatriated from Wuhan, the online circulation of scientific data and their effects during the health crisis, and the modes of communication in the context of an emerging disease, in order to better guide public policy.

French research in Europe

French research is also swinging into action at the European level with the coordination of the Rapid European COVID-19 Emergency Response (RECOVER) project. Funded by the European Commission, it involves 10 international partners and its multiple components include epidemiological, clinical, and social science studies.

France is also participating in the research projects Fight-nCoV (Fighting-Off Coronavirus (Sars-Cov-2) With Broad-Spectrum Antivirals: Establishing Animal Viral Challenge Model), I-MOVE-COVID-19 (Multidisciplinary European network for research, prevention and control of the COVID-19 Pandemic) and CoNVat (Combating 2019-nCoV: Advanced Nanobiosensing platforms for POC global diagnostics and surveillance).

Through the deployment of these high quality, ambitious and relevant research projects, the REACTing community is doing everything it can to tackle the challenges of Sars-CoV-2 spread and the ensuing impacts on health and society.

The selected projects





Mathematical modelling to anticipate risk of 2019-nCoV importation by geographical area.

Vittoria Colizza
Inserm, Sorbonne Université

 Pierre Louis Institute of Epidemiology and Public Health


Monitoring of a cohort of all infected patients in France: a viral kinetics study in untreated patients and a pharmacokinetics and pharmacodynamics (PK/PD) study of those receiving experimental therapies (remdesivir).

France Mentré
Inserm, Université de Paris, Université Paris 13

Infection, Antimicrobials, Modelling, Evolution (IAME) unit

Diagnostic, clinical and therapeutic research

Identification and characterization of human monoclonal antibodies neutralizing 2019-nCoV with the potential for development towards vaccine candidates.

Hugo Mouquet
Inserm, Institut Pasteur

Humoral Immunity unit

Human and social sciences

Use of the social sciences to inform public policy in terms of communication in the event of an emerging epidemic, based on social media treatment of the 2019-nCoV epidemic.

Laetitia Atlani-Duault
Inserm, IRD, Université de Paris

Health, Gender and Vulnerability in Developing Countries unit


Monitoring of subjects with confirmed exposure to the novel 2019 coronavirus through virology and immunology studies.

Xavier Duval
Inserm, Université de Paris, Université Paris 13

Infection, Antimicrobials, Modelling, Evolution (IAME) unit
Bichat Clinical Investigation Center

Fundamental research

Development of a replicon for coronavirus Covid-19.

Dr. Jean-François Eléouët


Molecular Virology and Immunology unit

Fundamental research

Potentiating existing nucleoside therapies.

Bruno Canardet Etienne Decroly

CNRS, Aix-Marseille Université

Architecture and Function of Biological Macromolecules laboratory

Fundamental research

Implementation of an experimental model of SARS-CoV-2 infection in the cynomolgus monkey.

Roger Le Grand
Inserm, CEA, Université Paris-Saclay

National Infrastructure for Biology and Health (IDMIT)

Diagnostic, clinical and therapeutic research

Establishment of an antibody profile in convalescing patients and preparation of a serological test applied to an epidemiological survey in people exposed to SARS-Cov-2.

Marc Eloit
Institut Pasteur

Pathogen Discovery laboratory

Diagnostic, clinical and therapeutic research

Evolution of SARS-Cov-2 in the human host during infection and humoral response.

Sylvie van der Werf
Institut Pasteur, CNRS

National Reference Center for Respiratory Viruses, Molecular Genetics of RNA Viruses

Fundamental research

Live animal and endangered wildlife markets: a study evaluating the risks of COVID-19 transmission in the Mekong Delta region.

Philippe Dussart
Institut Pasteur in Cambodia

Fundamental research

Role of furins in SARS-CoV-2 Spike protein maturation: evaluation of the antiviral potential of furin inhibitors

Bruno Coutard
Aix-Marseille Université, CNRS

Emergence of Viral Pathologies laboratory, Polytech Marseille

Diagnostic, clinical and therapeutic research

Strategy of repurposing medicines to treat 2019-nCoV infections

Bruno Lina
Inserm, Université Claude Bernard Lyon 1, École Normale Supérieure, CNRS

International Center for Research on Infectious Diseases – CIRI

Fundamental research

Proof of concept for the rapid production of recombinant SARS-CoV-2

Julien Mélade
Inserm, IRD, Aix-Marseille Université, French Blood Establishment, École des Hautes Études en Santé Publique

Emerging Viruses unit

Human and social sciences

The aim of the AEC2-France project is to document and analyze, through anthropology research, the organized confinement for French nationals repatriated from Wuhan, epicenter of the Covid-19 epidemic

Marc Egrot

IRD, Aix-Marseille Université

Population-Environment-Development laboratory

Human and social sciences

General population and healthcare professional knowledge, perceptions and behaviors in Metropolitan France in the face of the Covid-2019 epidemic

Thomas Hanslik
Inserm, Sorbonne Université

 Pierre Louis Institute of Epidemiology and Public Health

Fundamental research

Multidisciplinary project combining artificial intelligence methods with proteins biochemistry. Aims to (1) reconstitute the COVID-19 replication complex in vitro; (2) model it in silico and (3) test nucleotide analog inhibitors (active on other viruses) and protein inhibitors (nanobodies) that will target the protein/protein interactions.

Isabelle Imbert
Aix-Marseille Université, CNRS

Architecture and Function of Biological Macromolecules laboratory, Polytech Marseille

Diagnostic, clinical and therapeutic research

Implantation of an assisted ventilation protective mask: acceptability and incorporation in the organization of care.

Jean-Christophe Lucet

Inserm, Université de Paris, Université Paris 13

Infection, Antimicrobials, Modelling, Evolution (IAME) unit

Human and social sciences

The aim of this project, which mobilizes data collected online and via interviews, is to produce an analytical description of the circulation of scientific data and their principal effects and a framework of analysis combining scientific and political challenges with a view to future research projects.

Guillaume Lachenal

Science Po


Daniel Benamouzig

CNRS, Sciences Po

Center for the Sociology of Organizations

Diagnostic, clinical and therapeutic research

Randomized, multicenter, adaptive study of the efficacy and safety of treatments for hospitalized patients presenting with COVID 2019 infection

Florence Ader

Inserm, CNRS, Université Claude Bernard Lyon 1, École Normale Supérieure de Lyon

 International Center for Research on Infectious Diseases (CIRI)

Cancer: the immune system attacks tumors remotely

Video showing T lymphocytes (green) attacking a tumor (blue and orange). In vivo real-time experiments show how T lymphocytes act both locally and remotely within the tumor. © Ronan Thibaut and Philippe Bousso, Institut Pasteur / Inserm

How does the immune system act to limit tumor development? Using in vivo imaging tools, scientists from the Institut Pasteur and Inserm described the spatiotemporal activity of tumor-infiltrating T lymphocytes, both locally and remotely. Their research was published in the journal Nature Cancer on March 9, 2020.

Some cells in the immune system, like T lymphocytes, are capable of attacking cancer cells. Promising new therapies known as immunotherapies, recognized by the 2018 Nobel Prize in Medicine, attempt to boost the immune system’s response to cancer.

But how exactly do T lymphocytes act in tumors? T lymphocytes are killer cells that are capable of infiltrating a tumor and destroying cancer cells, one by one, through direct contact. This destruction of cancer cells is a highly local phenomenon that only occurs in the immediate vicinity of killer cells. But during these contacts, T lymphocytes also produce soluble molecules known as cytokines. Scientists from the Institut Pasteur and Inserm set out to understand the effect of one of these cytokines, known as interferon-gamma (IFN-γ), on the tumor microenvironment.

They used highly powerful imaging techniques to visualize, in real time and in vivo in mice, both the behavior of T lymphocytes and also the effect of IFN-γ within the tumor. The scientists observed that rather than acting locally, the cytokines spread rapidly within the tumor and affect cancer cells that may be distant from the T cells.

“This remote action within the tumor is very interesting because it enables T lymphocytes to act on a large number of cancer cells, especially those that may have developed mechanisms to escape the immune system,” explains lead author Philippe Bousso, an Inserm researcher and Head of the Dynamics of Immune Responses Unit at the Institut Pasteur.

In their research, the scientists also demonstrated that the number of T lymphocytes that successfully infiltrate the tumor is correlated with the quantity of cytokine produced and determines the extent of tumor cell response. A study of melanoma patient cells supports this model of remote action by immune cells. Stimulating this collective response could therefore represent a key target for future immunotherapy approaches.

Menstrual Toxic Shock Syndrome: Wearing a Tampon for More Than Six Hours Increases Risk

Tampon use is thought to currently concern around 60 to 80% of women in France. Credits: Josefin on Unsplash

Each year, some twenty cases of Staphylococcal toxic shock syndrome linked to tampon use are reported in France. Characterized by various symptoms, such as high fever and skin rash, it can lead to multiple-organ failure and death in the most extreme cases. Although its incidence remains rare, research teams from the International Center for Research in Infectious Diseases (Inserm/CNRS/ENS de Lyon/Université Claude Bernard Lyon 1) and the National Reference Center for Staphylococci (Hospices civils de Lyon/ Université Claude Bernard Lyon 1) have identified several risk factors, notably showing that wearing tampons for more than six hours or overnight is linked to an increased risk of toxic shock syndrome. This study was published in eClinicalMedicine on March 10, 2020.

Staphylococcal toxic shock syndrome associated with tampon use generated a lot of attention in the 1980s. Affecting almost 10 in 100,000 young women in the USA each year back then, its incidence has since fallen considerably thanks to the use of tampons made from cellulose fibers or cotton. Nevertheless, several cases are still being reported each year, on both sides of the Atlantic and primarily in adolescents. For the researchers it was therefore essential to identify the risk factors that increase the likelihood of developing this syndrome, especially since tampon use is thought to currently concern 60 to 80% of women in France.

Toxic shock syndrome is linked to the presence of Staphylococcus aureus in the vaginal microbiota of certain women, a bacteria which can produce the toxin TSST-1. However, the presence of this bacteria does not in itself explain toxic shock. The woman also needs to be using intravaginal protection (tampon, menstrual cup…) and she needs to lack the antibodies that are capable of fighting TSST-1. The fact that certain women fulfil these three risk criteria but do not develop complications suggests that the issue is not tampon use, but rather misuse.

In a study published in eClinicalMedicine, researchers from Inserm, CNRS, ENS, Université Claude Bernard Lyon 1 and Hospices Civils de Lyon, within the teams of the International Center for Research in Infectious Diseases and National Reference Center for Staphylococci, sought to identify the characteristics of tampon use that are linked to an increased risk of toxic shock syndrome.


Duration of wear

The study took the form of a questionnaire, completed by 55 tampon users who had toxic shock syndrome between 2011 and 2017, and by 126 control women who had never had it. The median age of the participants was 17, which reflects the fact that it primarily affects young women. The questions concerned the length of time for which they wear tampons, their reading of the package leaflet enclosed with the tampons, and the education they had received on the subject.

The researchers have shown that the risk of toxic shock syndrome doubles when tampons are worn for longer than six hours, and triples when worn overnight (whereby the duration of use can be up to eight hours or longer). In addition, not reading the instructions supplied with the tampons, or not respecting them, is also linked to an increased risk of toxic shock.

“In the USA, the FDA recommends not exceeding eight hours of use, which is generally also stated on the tampon packs sold in France. Our study is the first to challenge this duration. In addition, we also wish to draw attention to the need to improve the education of adolescents. It is often their mothers who educate them on this, and although they are quite capable of explaining how to use tampons, they are not always properly informed about the risk of toxic shock and how to prevent it”, emphasizes study leader, Gérard Lina.

While menstrual toxic shock syndrome mainly affects adolescents, with a peak at around 15 years of age, the authors of the study call for inclusion of the subject in school sex education lessons and for greater involvement of the healthcare professionals of these young patients, in order to get the prevention messages across.

When Stress Weakens the Immune Defenses

Cytomegalovirus (CMV) infection in a human being. In red and green, the natural killer (NK) cells try to make their way to the infected cell. Inserm/Jabrane-Ferrat, Nabila

In previous years, various studies have established a link between psychological stress and reduced immune defenses, but the mechanisms involved remained poorly elucidated. Sophie Ugolini, Inserm Research Director at the Center of Immunology Marseille-Luminy, and her colleagues at CNRS and Aix-Marseille Université have recently shown that such a link is to a large extent mediated by a type of receptor that binds to stress hormones: the β2-adrenergic receptor. Their findings have been published in Journal of Experimental Medicine.

For several years now, the scientific community has been interested in the effects of psychological stress on health. Studies have shown that when infection strikes, stress is linked to reduced immune defense system efficacy. With her team, Sophie Ugolini, Inserm Research Director at the Center of Immunology Marseille-Luminy (Inserm/CNRS/Aix-Marseille Université), has sought to explain the biological mechanisms behind this phenomenon. The researchers focused on receptors expressed on the surface of many of the body’s cells (including the immune cells) and which are specific to the stress hormones adrenaline and noradrenaline – the β2-adrenergic receptors.

To study their role, the team first reproduced a situation of chronic stress in mice by administering for seven days a molecule which, like the stress hormones, stimulates the β2-adrenergic receptors. They then exposed the animals to a virus from the herpes family, cytomegalovirus MCMV. The mortality rate of the “stressed” mice having received the molecule proved to be much higher than that of the untreated mice (90% versus 50%).

The researchers then evaluated the animals’ resistance to infection in the absence of these receptors. This involved taking mice that are genetically modified to be devoid of β2-adrenergic receptors and exposing them to cytomegalovirus. In these animals, the stress hormones could no longer bind to β2 receptors and as a consequence could no longer act. They presented much greater resistance to the viral infection (90% survival versus only 50% for the control mice). These initial findings therefore suggest that stimulation of the β2-adrenergic receptors by the stress hormones is responsible for the weakening of the immune system in situations of psychological stress.


Towards new therapeutic avenues

In order to better understand the mechanisms involved, the team also analyzed the immune response of the mice devoid of β2-adrenergic receptors. They observed an increased production of inflammatory cytokines – molecules produced by the immune cells which promote the elimination of viruses.

The researchers discovered that the β2-adrenergic receptors most particularly inhibit the response of certain immune cells, known as natural killer (NK) cells. Stimulated by the stress hormones, the β2-adrenergic receptors prevent the NK cells from producing a particular type of cytokine required in order to eliminate viruses.

We have confirmed in an experimental setting that the stress hormones that bind to the β2-adrenergic receptors reduce immune response, which involves a decrease in the production of certain inflammatory cytokines required to eliminate viruses”, specifies Ugolini. According to the researcher, this study could open up new therapeutic avenues. “By targeting the β2-adrenergic receptor, it would in some disease settings be conceivable to deactivate the immune brakes triggered by states of stress”, she concludes.

Buruli Ulcer: New Diagnostic Avenues for a Neglected Disease

Recent studies have shown that Mycobacterium ulcerans infection causes the aggregation of immune cells (B cells) around the infected areas. Using fluorescent staining, a mouse spleen section shows B cells (in blue) and two sub-populations of T cells (in green and red). Credits: CIML/INSERM/CNRS/Mailfert, Sébastien/Chasson, Lionel


Buruli ulcer is the world’s third most common tropical mycobacterial disease after tuberculosis and leprosy. Caused by Mycobacterium ulcerans, it leads to the destruction of skin tissue and the development of large ulcers which can affect entire limbs right down to the bone. Researchers from Inserm, Université de Nantes, Université d’Angers and CNRS at the Nantes-Angers Oncology and Immunology Research Center (CRCINA) studied the rare cases of spontaneous healing from this disease in order to better understand its mechanisms. In addition to publishing their findings in the journal Science Advances, the team has filed a patent, opening up avenues for the deployment of hitherto inexistent diagnostic tools.


Buruli ulcer is a disease caused by Mycobacterium ulcerans (M.ulcerans), whose mode of transmission to humans is still not known. This bacterium produces a toxin called mycolactone which destroys skin cells and prevents the immune system from mounting an effective response, leading to the propagation of disease-characteristic ulcers on the limbs. Incapacitating and stigmatizing, Buruli ulcer affects children and adolescents most particularly. This little-known this disease is especially prevalent in West and Central Africa and has a very poor diagnostic and therapeutic arsenal. The World Health Organization (WHO) has classified it as a neglected tropical disease. Antibiotic treatment is effective if the disease is diagnosed quickly, although this is not yet possible in the majority of cases.

As part of a study published in Science Advances[1], a team led by Inserm researcher Estelle Marion at Nantes-Angers Oncology and Immunology Research Center (Inserm/Université de Nantes/Université d’Angers/CNRS) used mice to investigate the phenomenon of spontaneous healing that is observed in around 5% of infected patients.

Until now, research into Buruli ulcer focused on whole-body immune response. However, recent skin tissue studies have revealed that Mycobacterium ulcerans infection causes the aggregation of immune cells (B cells) around the infected areas. With this in mind, the researchers decided to focus on local immune response, at the site infected by the bacterium.

B cells produce a family of antibodies known as immunoglobulins (Ig). The major subgroups are IgA – found mainly in the mucous membranes and epidermis, IgM – present on the surface of the lymphocytes and for which a high count is synonymous with an ongoing infection, and IgG – the most numerous, which circulate primarily in the blood and eliminate foreign bodies encountered there.

Towards a diagnostic avenue

The researchers worked with two types of mice – one with the ability to spontaneously heal from Mycobacterium ulcerans infection, the other without. They began by studying immune reaction during infection, including during the spontaneous healing process, by analyzing skin samples from the area close to the infected site.

In both types of mouse, the level of cutaneous immunoglobulins increases during infection, but not to the same extent. In those unable to heal, IgM predominate, whereas in those able to heal, IgG predominate.

The researchers showed that these IgG bind to the toxin mycolactone. They went on to discover that only the mice that heal produce a very particular sub-type of IgG, IgG2a – capable of neutralizing the action of mycolactone. Finally, the researchers discovered the presence of the latter in the tissues of patients infected with M. ulcerans.

 “This study suggests for the first time that the body could efficiently respond to Mycobacterium ulcerans infection thanks to the production of antibodies that are capable of recognizing and neutralizing the toxin secreted by the mycobacterium. Although therapeutic avenues are still a long way off, this research offers new diagnostic ones”, concludes Inserm researcher Estelle Marion, who led this study.

According to the priorities issued by WHO, the team is envisaging the development of a quick and simple diagnostic test strip, based on the detection of antibodies recognizing mycolactone, thereby indicating M. ulcerans infection.

[1] This research was funded by Fondation Raoul Follereau, the French National Research Agency, the Pays de la Loire region, Université d’Angers, and Inserm (ATIP – Avenir Program).