The Record Heat of Summer 2022 Caused Over 61,000 Deaths in Europe, With Nearly 5,000 in France

Europe is the continent experiencing the greatest warming, up to 1°C above the global average. © Adobe Stock

The summer of 2022 was the hottest ever recorded in Europe, characterized by an intense series of heatwaves that beat records of temperature, drought, and forest fires. Although Eurostat had already reported unusually high excess mortality for these dates, the fraction of mortality that could be attributed to the heat had not until now been quantified. And this is precisely what a study by scientists from Inserm and the Barcelona Institute for Global Health (ISGlobal) set out to do. Their analysis estimates that between May 30 and September 4, 2022 there had been 61,672 heat-related deaths in Europe. These findings suggest that our current strategies for adapting to heatwaves may still be insufficient. The full study has been published in Nature Medicine.

In 2003, Europe experienced one of the most intense heatwaves in its history, causing over 70,000 deaths. Since then, adaptation strategies have been developed in an attempt to respond quickly to intense heat and protect the most vulnerable populations. Given the continuous increase in heatwave episodes in recent years and the estimations that they could double in number by 2050, it is crucial to better characterize the mortality associated with them and evaluate the efficacy of the strategies put in place.

With the summer of 2022 being the hottest ever recorded in Europe, scientists from Inserm at the France Cohorts JSU[1] and the Barcelona Institute for Global Health looked at the number of heat-related deaths for this period.

The research team obtained temperature and mortality data for the 2015-2022 period in 823 regions of 35 European countries, representing a total population of over 543 million people. These data were used to estimate epidemiological models to predict heat-related mortality for each region and week of the summer period.

The records first revealed that the temperatures were above average throughout all the weeks of the summer period. The largest heat-related abnormality was recorded between July 11 and August 14, during which, according to the researchers, 38,881 deaths were caused by the heat. In this period, there was a particularly intense pan-European heatwave between July 18 and 24, for which a total of 11,637 deaths were attributed to the excess heat. All in all, the analysis reveals that between May 30 and September 4, 2022 there would have been 61,672 heat-related deaths in Europe.

France is the country that recorded the greatest increase in temperature compared with the seasonal averages, with +2.43ºC above the average values for 1991-2020, followed by Switzerland (+2.30ºC), Italy (+2.28°C), Hungary (+2.13ºC) and Spain (+2.11ºC).


Analyses by Country, Age and Sex

Based on the epidemiological models they built, incorporating data on temperature and number of deaths[2], the scientists were also able to propose a country-specific analysis. They showed in absolute terms that the country with the largest number of heat-related deaths throughout the summer of 2022 was Italy, with a total of 18,010 deaths, followed by Spain (11,324), and Germany (8,173). France comes in 4th place with 4,807 heat-related deaths[3].

Beyond the estimated number of heat-related deaths, the study also included an analysis based on age and sex. At European level, the results highlight a very marked increase in mortality in the upper age groups, with the vast majority of deaths concentrated in the age range of 80 and over.

For the sex-based analysis, the data show that heat-related premature mortality was 63% higher in women than in men. This increased vulnerability of women to heat is observed in the general population and above all among the over-80s, where the mortality rate is 27% higher than that of men. In contrast, the male mortality rate is 41% higher among those under 65 and 13% higher between the ages of 65 and 79.

For the research team, these findings should encourage us to take action to implement more robust preventive and protective measures. Indeed, the fact that many countries already had active prevention plans, unlike in 2003, suggests that the adaptation strategies available to us today may still be insufficient.

“The acceleration of warming observed over the past ten years underlines the urgency of in-depth re-evaluation and reinforcement of prevention plans, paying particular attention to the differences between European countries and regions, as well as between age and sex, which currently mark the differences in vulnerability to heat,” explains Hicham Achebak, Inserm researcher and last author of the study.

Europe is the continent with the highest level of warming, up to 1°C more than the world average. In this context, the team’s estimates also suggest that in the absence of an effective adaptive response, the continent will face an average of over 68,000 excess deaths each summer by 2030 and over 94,000 by 2040.


[1] The France Cohorts Joint Service Unit (JSU) brings together several academic supervisory bodies, including Inserm, Ined, Université Paris-Saclay, Université Paris Cité, and Sorbonne Université. Its long-term objective is to offer a range of services for epidemiological cohorts.

[2] The mortality data were obtained via Eurostat and the temperature data via ERA5-land reanalysis.

[3] This study focuses on heat-related mortality during the summer of 2022 using weekly data and estimated nearly 5,000 deaths in France. On the other hand, Santé Publique France has recently used daily data for the same period and estimated nearly 7,000 deaths. This difference is due to the fact that the weekly data generally underestimate the impact of heat on mortality.

A Major Advance in the Genetics and Risk Factors of a Form of Infarction That Mainly Affects Women

SCAD is a form of infarction that mainly affects women. © Fotalia


Spontaneous coronary artery dissection, more commonly known under the acronym SCAD, is a cause of infarction of which 9 out of 10 of its victims are women in their forties in apparent good health. Still poorly understood, it is often underdiagnosed, which complicates treatment despite the fact that it could represent up to one third of infarction cases in women under 60 years of age. In order to understand its genetic causes and biological mechanisms, a new international study led by Inserm Research Director Nabila Bouatia-Naji at the Paris-Cardiovascular Research Center – PARCC (Inserm/Université Paris Cité) was set up. Its findings show the genetic causes that define the risk of SCAD to be very numerous and distributed across the entire patient genome. The study has identified 16 genomic regions associated with a higher risk of SCAD, paving the way for a better understanding of the biological mechanisms that underlie this disease. The study was published on May 29, 2023 in Nature Genetics.

Unlike the majority of cardiovascular diseases, such as myocardial infarction, which mainly affect older and/or overweight men, spontaneous coronary artery dissection (SCAD) is a form of infarction that affects women in 9 out of 10 cases. Although these women are often in their forties, the disease can occur earlier – in the year after giving birth, or later – during the transition to menopause. Despite being increasingly recognized as a major form of infarction within this population, SCAD remains quite poorly documented due to a lack of data and a lack of knowledge of its specific risk factors – particularly genetic.

Over the past 20 years, considerable progress has been made in detailing the mechanisms of development of coronary diseases such as atherosclerosis and the very rare and syndromic forms of cardiovascular diseases. Such knowledge is essential in order to better understand these diseases and devise improved and personalized strategies for their prevention and treatment.

Nevertheless, research has lagged far behind in the understanding of diseases such as SCAD that affect women at key stages of their lives. It is therefore essential to now focus on this understudied cardiovascular disease and its own specific genetic risk.

The team of Inserm geneticist Nabila Bouatia-Najia conducted a large-scale study on the subject, coordinating a meta-analysis of 8 genome-wide association studies (GWAS)[1].  By comparing the genetic data of over 1900 patients with around 9300 healthy individuals, the scientists identified 16 genomic regions (or loci) of genetic predisposition to SCAD.


Towards a Better Understanding of the Biological Mechanisms

This study began by showing that the genetic variations most commonly found in patients having survived SCAD play a role in the composition of the “cement” that surrounds the coronary artery cells.

However, one of the genes identified is F3 and it encodes the tissue coagulation factor. Normally, the tissue factor initiates coagulation at cell level in order to resorb any hematomas. The results of the study suggest that a lack of F3 expression is often found in patients, constituting a potential cause of poor artery repair, which can lead to tearing. Poor hematoma resorption would therefore be a hitherto unknown genetic cause.

One of the other objectives of this study was to position SCAD in relation to other cardiovascular diseases in order to better understand its epidemiological particularities. Using the data that determine genetic cardiovascular risk factors and clever statistical methods, the scientists revealed a robust link between high blood pressure and risk of SCAD, while confirming that high cholesterol, overweight, and type 2 diabetes had no impact on this risk.

“This finding could therefore be clinically interesting in the longer term, to encourage doctors to closely monitor blood pressure changes in patients at increased genetic risk of SCAD,” explains Bouatia-Naji, Inserm Research Director and last author of the study.

Finally, this study reveals a genetic link between SCAD-related infarction and atherosclerosis-related infarction. Indeed, the researchers have shown that a large number of genomic regions predisposing to SCAD are shared with those of atherosclerosis-related infarction. However, even if these were the same genetic variants, the alleles[2] that are more common in SCAD patients are routinely described as being less common in subjects with atherosclerosis-related infarction.

“This finding is very surprising because they show that, depending on whether you are faced with a young woman with no risk factors, or an older man with risk factors, the genetic causes and biological mechanisms associated with their infarction can be opposed.  Our findings highlight the need to better understand the particularities of cardiovascular diseases in young women in order to improve their follow-up, which is currently identical to that of atherosclerosis-related infarction,” concludes Bouatia-Naji.

Building on these findings, the team is now working to develop new cell and animal models that better account for the genetic factors involved in the disease, particularly in order to better study their impact on the condition of the arteries. Always with a longer-term objective in mind: to shed the spotlight on a cardiovascular disease that is essentially female and all too often neglected, and to improve how it is understood and treated.


[1] Genome-wide association study, widely performed for several years now, which consists of analyzing the entire genome of thousands of healthy and sick individuals in order to identify the genomic regions which contain the genes influencing the vulnerability of people to the condition in question

[2] An allele is a version of a genetic variant resulting from a change in the DNA sequence. Any DNA sequence can have several alleles, which often determine the appearance of different hereditary characteristics.

Women and Parkinson’s Disease: Physical Activity Found to Be Beneficial More Than Twenty Years Before Diagnosis

marche sportive retraitée© AdobeStock

Although physical activity is regularly discussed as being one of the avenues for preventing Parkinson’s disease (PD), studies so far had been unable to eliminate certain biases or had not focused on its specific role in women. Researchers from Inserm, Université Paris-Saclay and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ) with the Gustave Roussy Institute studied the impact of physical activity on the development of PD in nearly 100,000 women from the French cohort E3N followed up over 29 years. They observed that the more the participants had been active in their lives, the lower was their risk of developing the disease – with such a benefit already present more than 20 years before diagnosis. The researchers have also shown that in women with PD there had been a significant decrease in physical activity in the 10 years prior to diagnosis, probably due to bothersome precursor symptoms. These findings, to be published in Neurology, call for consideration to be given to the rollout of preventive physical activity-based programs in people at risk of PD.

Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by the destruction of certain neurons in the brain and the accumulation of proteins toxic to them. It is the second most common neurodegenerative disease in France and there is still no cure; therefore it is essential to identify avenues for prevention.

Previous studies had shown a reduced risk of developing PD in people with who engage in high levels of physical activity. However, the limited number of such studies involving women did not make it possible to confirm this association in that population. In addition, these studies generally had a relatively short participant follow-up period with only one evaluation of physical activity, which did not make it possible to eliminate certain biases – particularly that of reverse causation.

Reverse causation is expressed as follows: precursor symptoms of PD (constipation, sleep disorders, smell disorders, subtle motor signs, etc.) may be present several years before the disease is diagnosed. Their effects could lead people to modify their behavior (such as how much physical activity they do) prior to diagnosis, which is liable to distort the statistical analyses that study the relationship between these behaviors and the risk of developing the disease.

A team led by Alexis Elbaz, Inserm researcher at the Epidemiology and Population Health Research Center (Inserm/Université Paris-Saclay/UVSQ), studied the impact of physical activity on the onset of PD in women from the E3N cohort over a follow-up period of 29 years. E3N is a French cohort of nearly 100,000 women who have been followed-up since 1990. With nearly 1,200 women with PD identified in 2018[1], it is currently the world’s largest female prospective cohort for this disease.

The changes in the physical activity[2] of each participant throughout the 29 years of follow-up were estimated based on the information collected via six individual questionnaires completed at different stages of the follow-up. The data obtained compared the practice of physical activity prior to diagnosis in the participants with PD with those of the participants of the same age without PD.

In order to reduce the risk of a reverse causation bias resulting from the potential influence of the precursor symptoms on physical activity in the years prior to diagnosis, the scientists examined the impact of physical activity evaluated more than 5, 10, 15 and 20 years prior to diagnosis on the risk of developing PD.

What they observed was that the more physically active the participants, the less likely they were to develop PD, even when the physical activity had been evaluated more than 20 years before diagnosis. The most active women therefore had a 25% less risk of developing the disease compared with the least active.

Overall, the participants with PD had been less active than the others throughout the follow-up period, including more than 20 years before diagnosis. This gap between women with and without PD increased further in the 10 years before diagnosis, suggesting that the precursor symptoms occurring in this interval could indeed be responsible for a decrease in physical activity in the women who will go on to develop the disease but who have not yet been diagnosed.


“These findings support the protective effect in women of physical activity against the risk of developing Parkinson’s disease, even over the very long term, specifies Berta Portugal, PhD student and first author of this research. They support the utility of implementing physical activity programs to prevent Parkinson’s disease in people at risk and call for conducting other studies in order to understand what activity type and level of intensity are the most beneficial,” she adds.


“This study demonstrates the importance of studies with a lengthy follow-up within large-scale cohorts to better account for the precursor symptoms and the statistical bias they cause in evaluating the benefit of physical activity on the development of Parkinson’s disease,” concludes Elbaz.


[1]The percentage of women with PD in the cohort is similar to that of the general population in Europe over the same period of time.

[2]The concept of “physical activity” goes beyond sport alone. In this study, it is quantified by the distance walked daily, the number of flights of stairs climbed, journeys taken by bicycle, time spent doing light and heavy household activities, time spent doing recreational activities, whether light (gardening, sports of moderate intensity) or vigorous (intensive sports).

Eating Broccoli to Limit Skin Allergies


The scientists specifically focused on dietary compounds naturally present in cruciferous vegetables, such as broccoli. © Unsplash

The severity of skin allergies can vary depending on many environmental factors, including diet. However, the role of specific nutrients had not been well documented until now. In a new study, researchers from Inserm and Institut Curie at the Immunity and Cancer[1] unit have shown that the absence in the diet of compounds found in certain vegetables, particularly broccoli and cabbage, could worsen skin allergies in animal models. These findings, published in Elife, highlight the importance of a balanced diet alongside therapeutic interventions offered to patients.

Skin allergies are caused by an inappropriate immune response to compounds present in the environment, with the extent of their severity varying according to many factors, including diet. However, the impact of the different compounds present in food is still poorly understood, which complicates the use of nutrition-based strategies to alleviate patient symptoms.

In this research, the scientists focused on dietary compounds that act on a molecule present in the body called the aryl hydrocarbon receptor (AhR). Such nutrients are naturally present in cruciferous vegetables, such as broccoli.

While previous studies had already shown an association between these dietary compounds and the worsening of inflammatory bowel disease and neuroinflammation, their effect on allergic immune reactions had not been documented until now.


Worsening Allergies

The research team used a mouse model of skin allergy. Some of the animals were fed a diet containing no AhR-activating compounds in order to evaluate its potential impact on the severity of their allergy.

The researchers showed that the absence of these nutrients is associated with an increase in the skin’s inflammatory state and a worsening of the skin allergy, which did not occur in the mice whose diet contained those compounds.

The scientists wished to go further in order to understand the biological mechanisms of action of these nutrients. When the nutrients were absent, they observed the overproduction of a molecule called TGF-beta in the epidermis of the mice. This overproduction disrupts the normal functioning of a population of immune cells called “Langerhans cells”, which are exclusively present in the skin and act as a modulator of skin immune responses.

The scientists then validated these findings by showing that the AhR-activating compounds also control TGF-beta production in human skin cells.

“Our results suggest that an imbalanced diet could increase allergic skin reactions in humans through mechanisms that we have described precisely. In essence, we could say that our research helps to explain why eating vegetables such as broccoli and cabbage may limit the severity of skin allergies and why it is therefore important to include them in one’s diet,” emphasizes Inserm researcher Elodie Segura, who led this study at Institut Curie.

The findings of this study may also apply to other skin diseases in which inflammatory mechanisms are involved, such as psoriasis. Furthermore, they also open up interesting research avenues for improving the study of the gut-skin axis in the development of allergic diseases.

Based on these data, the research team now wishes to look at the role of AhR-activating dietary compounds in other inflammatory disease settings, such as tumors.


[1] Conducted at the Immunity and Cancer unit (Inserm, Institut Curie), this research was carried out with particular thanks to Institut Curie’s experimental pathology platform and new metabolomics and lipidomics platform.

Health Outcomes of the Nuclear Tests in French Polynesia

Polynésie française

Between 1966 and 1974, France performed 41 atmospheric nuclear tests in French Polynesia. © Unsplash

The health outcomes of the nuclear tests performed in French Polynesia in the 1970s have been the subject of epidemiological studies at Inserm for several years. Previous research published by a team from Inserm and Université Paris-Saclay with the Gustave-Roussy Institute had studied the relationship between the frequency of thyroid cancer in French Polynesia and the atmospheric nuclear tests performed by France. It had found a very probable slight increase in the thyroid cancer risk with the radiation dose received following the nuclear tests. In a new publication, the scientists confirm these findings and conduct a risk prediction analysis showing that these nuclear tests could be responsible for 2.3% of the thyroid cancer cases. The particularity of this study, whose results have been published in JAMA Network Open, lies in the access to the original internal reports by the radiation-protection services that relate to 41 atmospheric nuclear tests performed by France between 1966 and 1974 in French Polynesia, declassified by the French military in 2013.

Between 1966 and 1974, France conducted 41 atmospheric nuclear tests in Polynesia. For several years, research teams have attempted to evaluate the potential consequences of the radioactive fallout on population health. They have particularly focused on diseases that may be radiation-induced, such as cancer, cardiovascular diseases, and cataracts.

In an Inserm Collective Expert Review produced in 2021 (only available in French), researchers mentioned two epidemiological studies published on the subject, one of which concerns the risk of developing thyroid cancer. Due to the amount of radioactive iodine released in nuclear tests and its active absorption by the thyroid, this form of cancer is the most serious health risk for the population living near the nuclear test sites.

This is because when radioactive iodine binds to the thyroid instead of natural iodine, it exposes the gland to the radiation it emits. If high levels of this radioelement are found in the thyroid, this radiation may damage the DNA and lead to the development of cancerous tumors.

In a study published in 2010 in the British Journal of Cancer, researchers from Inserm and Université Paris-Saclay at the Center for Research in Epidemiology and Population Health (CESP) at the Gustave-Roussy Institute compared the radiation exposures of 229 Polynesians diagnosed with differentiated thyroid carcinoma between 1981 and 2003 with those of 373 “control” individuals who had not developed thyroid cancer in the same population. This case-control study conducted in the local population had shown a small increase in the risk of thyroid cancer in line with an increase in the dose received by the thyroid before the age of 15.

Although these findings are insufficient in providing a firm conclusion on the links between the fallout of the atmospheric nuclear tests and the occurrence of radiation-induced diseases in French Polynesia, they also did not rule out the existence of health impacts.

Continuing this research, the same team conducted a second epidemiological study, this time on 395 cases of thyroid cancer diagnosed between 1984 and 2016 in Polynesia and 555 controls from the general population. For the first time, they had access to the original radiation-protection service reports relating to the 41 atmospheric nuclear tests performed by France between 1966 and 1974 in French Polynesia, declassified by the French military in 2013.

Thanks to these declassified documents, meteorological data, and interviews with cases and controls (population movements, dietary habits, etc.), the researchers were able to simulate the radioactive cloud of each nuclear test and estimate the dose of radiation received to the thyroid of the study participants. This was on average 4.7 milligray for the cases and 4.6 milligray for the controls.

For all of the cancer cases (395 people), the scientists did not find a significant association between the dose of radiation received by the thyroid and the risk of thyroid cancer. However, the relationship was significant if the analysis only considered the invasive cancers requiring treatment, and excluded the noninvasive microcarcinomas that are common and usually do not need surgery.

Using these cross-referenced data (population movements, dietary habits and rates of thyroid cancer incidence), the researchers also made a risk prediction and showed that, based on current risk models, the nuclear tests performed by France could be responsible for a total of 2.3% of all thyroid cancer cases (confidence interval between 0.6 and 7.7%[1]).

“These findings are consistent with our previous conclusions and confirm that the nuclear tests are most likely responsible for a small increase in the incidence of thyroid cancers in French Polynesia. However, these findings should be considered with caution as the estimated radiation doses received by the thyroid over 50 years ago are bound to be inaccurate,” explains Florent de Vathaire, Inserm researcher at Gustave-Roussy, and first author of the study.

The scientists are continuing their research with the aim of adding to their analysis the evaluation of the genetic susceptibilities of the populations (hereditary factors and genetic combination specific to each individual) that could affect the development of thyroid cancers in the region.


[1] The confidence interval defines a minimum and maximum value between which, for a given risk of error, the exact value of the entire population is situated.

AI: A New GPT-Inspired French Algorithm Improves Trauma Surveillance

hôpital urgences

Scientists have developed an algorithm to better understand the traumas that represent one third of emergency department visits. © Unsplash

In France, one third of emergency department (ED) visits are the result of trauma. In order to better understand the mechanisms and improve the management of trauma, researchers from Inserm and Université de Bordeaux at the Bordeaux Population Health Research Center, with teams from Bordeaux University Hospital, have developed an algorithm capable of classifying ED visits for trauma through the artificial intelligence (GPT) analysis of clinical reports. This project, called TARPON[1], which has achieved performance accuracy levels of 97%, is described in the Journal of Medical Internet Research Artificial Intelligence. With these findings, the imminent establishment of a national trauma observatory can be envisaged.

Trauma accounts for 9% of mortality in France and often affects populations of young people. More than one third of the 21 million annual emergency department (ED) visits are for trauma. It is therefore a major public health problem that represents a significant health, social and economic burden for which the scientists are working to provide solutions.

The idea for the TARPON project conducted by researchers from Inserm and Université de Bordeaux with Bordeaux University Hospital is based on the observation that the medical staff write a report for each ED visit. These reports represent a wealth of information: symptoms, patient condition, as well as many details on the circumstances in which the trauma occurred.

However, these data remain untapped, with few statistics available on victims of daily life accidents, violence or suicide attempts. For road accidents, an observatory exists, but it is only complete for mortality and the majority of accidents related to cycle, pedestrian or scooter travel are not included. Therefore, the analysis of anonymized information from ED reports would make it possible to constitute the basis for a virtually-exhaustive trauma surveillance system.

These reports are unstructured texts written using a mixture of everyday, medical and technical terms, as well as abbreviations. In order to extract the relevant information without having to read them all, the research teams have developed an automatic language-processing technique based on artificial neural networks. They have adapted the GPT artificial intelligence model and trained it with a sample of over 500,000 reports from adult emergencies at Bordeaux University Hospital[2]. The result is a French-speaking clinical language-processing tool that is compliant with GDPR.

With the support of the Health Data Hub, Bpifrance, the Nouvelle Aquitaine region, the French medicines agency (ANSM) and the Road safety delegation (DSR), the researchers were able to fund the purchase of a powerful server dedicated to artificial intelligence and installed in the hospital itself. This server has been used to implement the algorithm developed by the scientists, in order to automatically classify trauma by type – with surprising precision.

The method developed by the researchers makes it possible to correctly classify 97% of the reports (compared with 86% using the former methods), as described by the researchers in their scientific article. Thanks to this first step, it will be possible to begin studying this data on the Health Data Hub’s technology platform by this summer.

These findings pave the way for the establishment of a national trauma surveillance system, as well as epidemiological analyses concerning, for example, the impact of medication use on the risk of accidents. Research which should therefore provide new insight into major public health issues. In the immediate future, TARPON will be extended to include fifteen EDs across the entire French territory.


[1] TARPON: Automatic processing of ED summaries to create a national observatory

[2] This research meets the obligations of the General Data Protection Regulation (GDPR).

Long COVID: The Persistence of SARS-CoV-2 in the Mucous Membranes May Be A Factor


This transmission electron microscope image shows SARS-CoV-2, isolated from a patient in the U.S., emerging from the surface of cells cultivated in a laboratory. © National Institute of Allergy and Infectious Diseases-Rocky Mountain Laboratories, NIH. Public domain.

Several months after infection with SARS-CoV-2, some patients still have symptoms: a phenomenon commonly referred to as “long COVID”. In new research, teams from Inserm and Université Paris Cité[1], in collaboration with the University of Minho in Braga (Portugal), have shown that this could be explained biologically by abnormalities of the immune system associated with the persistence of the virus in the mucous membranes. These findings, published in Nature Communication, could in the longer term pave the way for a diagnostic tool for long COVID.

Despite the fact that various studies consider long COVID to affect between 10 and 30% of people infected with SARS-CoV-2, its diagnosis and treatment remain difficult. The team of Inserm researcher Jérôme Estaquier, in collaboration with that of Ricardo Silvestre at University of Minho in Portugal, is conducting research to explain this phenomenon from the biological point of view.

At the present time, few biological criteria, apart from the persistence of symptoms beyond three months after the acute infection, enable its diagnosis. Once a patient is not fully recovered after this period, they are considered to have long COVID. Without a more reliable means of diagnosis, it is difficult to offer the appropriate care.

In order to better understand long COVID and find diagnostic markers, the researchers studied the immune systems of 164 people six months after they were infected.  They analysed the blood samples of 127 people, half of whom with long COVID (fatigue, shortness of breath, cough, muscle or chest pain, anxiety, etc.) and those of 37 controls who had not been infected.

The researchers focused on certain immune cells, namely the T cells (including CD8 cells) involved in eliminating the virus, and the SARS-CoV-2 antibodies. In addition, they had blood samples that were taken during the acute phase of the disease for 72 of these patients, enabling them to retrospectively compare the level of inflammation at the early stage in those who went on to develop long COVID or not.


Several immune markers identified

The researchers identified a number of blood markers present six months after infection in 70-80% of the subjects with long COVID, while those same markers were rare in the subjects who had not developed it.

In particular, the teams showed that a CD8 cell subtype expressing the inflammatory protein granzyme A is present in excess, whereas another CD8 subtype, this time expressing integrin b7, is present in small quantities. Yet it is the latter subpopulation that is essential for controlling viruses in the mucous membranes. In addition, virus-specific IgA antibodies are also present in excess whereas they should be rapidly eliminated if the virus is absent. These observations suggest the persistence of the virus in the body and especially in the mucous membranes.

The researchers hypothesise that SARS-CoV-2 could make itself at home in the intestinal mucosa as it is more “permissive” in immune terms than the rest of the body, insofar as the virus has to tolerate the bacterial flora. Other viruses, such as HIV, also use this escape strategy. Initially present in the lung mucosa, SARS-Cov-2 could therefore descend to the intestine and persist there without the immune system being able to eliminate it completely.

In the final stage of the study, when evaluating the initial level of inflammation during the acute phase, the scientists observed an association between an inflammatory response characterized particularly by very high levels of interferon IP-10 or interleukin IL-6 and the risk of going on to develop long COVID.

“This confirms clinical observations that the initial severity of COVID is associated with a higher risk of developing long COVID,” specify the researchers. “One hypothesis is that people with more exacerbated early immunodeficiency develop more severe initial forms of COVID-19 and fail to effectively eliminate the virus that passes into the intestinal mucosa, where it settles for a long time. The immune system kind of ends up tolerating it at the cost of persistent symptoms of varying intensity and nature,” explains Estaquier.

The objective is now to validate these findings in new cohorts to determine whether some of these markers could be used as a diagnostic tool.

“If measuring IgA some time after the acute phase and potentially CD8 b7 cells was able to diagnose long COVID, doctors could make an objective diagnosis. Then we could think about therapeutic targets based on this research,” concludes Estaquier.


[1]This research in France was supported by the Fondation pour la Recherche Médicale, the French National Research Agency (ANR), and ANRS | Emerging Infectious Diseases.

Hypertension: A Mixture of Air Pollutants Could Cause Repeated High Blood Pressure Peaks

Pollution de l'airAir pollution is an acknowledged environmental factor in high blood pressure. © Adobe Stock

Air pollution is an acknowledged environmental factor in high blood pressure. It consists of a mixture of particles and gases whose combined effects on human health are not yet well known. A team from Inserm and Sorbonne Université, assisted by international collaborators, used continuous monitoring to study the daily life impact of a mixture of five air pollutants on the blood pressure of 221 MobiliSense[1] study participants in the Greater Paris area. With two models – one taking into account variations in ambient air pollutant levels, the other variations in the amounts inhaled – the researchers observed an association with acute repeated blood pressure increases. This study, published in Environmental Research, paves the way for a better understanding of the link between air pollution and hypertension.

Hypertension is a chronic disease that affects one in three adults. Linked to abnormally high pressure of the blood in the blood vessels, it can lead to cardiovascular, cerebrovascular, and even neurodegenerative complications.

Previous studies have shown that some air pollution molecules affect blood pressure and could therefore promote hypertension. However, in everyday life, the air pollution to which people are exposed generally consists of mixtures of air pollutants rather than a single component in isolation – mixtures that had been little researched until now.

An international team led by Basile Chaix, Inserm Research Director at the Pierre Louis Institute of Epidemiology and Public Health (Inserm/Sorbonne Université), wanted to characterize the effects on blood pressure of the daily-life exposure to a mixture of five air pollutants – black carbon, nitrogen dioxide (NO2), nitrogen oxide (NO), carbon monoxide (CO), and ozone (O3) – in 221 participants from the MobiliSense study.

In order to study the effects of this complex mixture, the research team developed new monitoring methods and used innovative measuring equipment. Each participant wore an ambulatory blood pressure measurement device[2], two portable sensors to continuously measure pollutants in the ambient air near the breathing zone, a GPS tracker to record mobility, and an accelerometer to measure physical activity and thus estimate the ventilation rate[3] (the volume of air inhaled or exhaled per unit of time). The measurements were taken over one day in the lives of the participants.

Their blood pressure was measured every 30 minutes in order to observe as closely as possible the time between variations in ambient air pollutant levels, the estimated amount of pollutants inhaled, and their potential impact on blood pressure.

Learn more about blood pressure and hypertension

Blood pressure results from the ejection of blood from the heart into the blood vessels and consists of the pressure it exerts on the vessel walls. It is characterized by two values:

  • the upper value or systole (systolic blood pressure), measured when the heart contracts. This pumps blood through the aorta to the peripheral arteries;
  • the lower value or diastole (diastolic blood pressure), measured when the heart relaxes. This enables the cardiac ventricles to receive the blood that enters the atria through the vena cava- and pulmonary veins.

Hypertension is when the resting systolic value is above 140 mmHg and/or the resting diastolic value is above 90 mmHg.

The researchers observed that when the levels of all the pollutants in the mixture increased within the 5 minutes prior to measuring blood pressure, there was an increase in systolic pressure (see box). A similar association was also found between an increase in the amount of pollutants inhaled within the 5 minutes prior to measuring blood pressure (related to an increase in the concentrations measured and/or physical activity and therefore in the ventilation rate) and an increase in systolic pressure.

“We chose to consider short windows of exposure (5 min, 15 min, 30 min, 1 hour) to study the time between exposure to pollution and blood pressure response, specifies Chaix. Here we see that the association is weaker when the exposure is observed over windows longer than 5 minutes, which indicates the immediacy of the blood pressure elevation in response to increased levels of air pollutants in the studied mixture,” adds the researcher. He continues: “These repeated increases in blood pressure linked to exposure to air pollutants in urban areas when out and about could contribute to a chronic rise in blood pressure, month after month, year after year. “

Another observation from these two models is that – when we consider the individual contribution of each pollutant to the effect of the mixture on blood pressure – ozone and black carbon present as being the greatest contributors to its increase.

With few existing studies having used these measurement and modeling methods to study mixtures rather than isolated pollutants, the research team clarifies that it does not currently have the possibility to compare its findings with other research, which means that they should be interpreted with caution.

However, should these findings be confirmed, it may be possible to extrapolate them to the populations of other major European cities whose pollution levels are similar to those of Greater Paris.

As for the implications of the study, Chaix concludes: “Our findings call for air pollution to be considered as a cause of hypertension and for the rollout of public policies aimed at reducing exposure to this pollution in everyday life – and particularly that of road traffic in the heart of our towns and cities. “

Next on the agenda is for the team to explore the physiological mechanisms and causes behind the associations observed in this study.


[1]The MobiliSense study is conducted on inhabitants of the Greater Paris area and aims to explore the effects of air and noise pollution exposure on cardiovascular and respiratory health.

[2]Unlike the blood pressure measurements taken when the individual is in a resting state, ambulatory blood pressure measurements are taken throughout the day and during the course of the individual’s activities using a wearable device.

[3]In previous studies, the team had shown that the amount of polluted air inhaled was not directly proportional to the levels of pollutants in the breathing zone but was also dependent on the ventilation rate, which varies with the intensity of physical activity. The ventilation rate was therefore estimated for each participant based on the accelerometer measurements.

Using Modeling to Limit Infectious Disease Transmission at Airports and Train Stations

The model concerns London Heathrow airport. © Unsplash

In crowded places, such as airports and train stations, social distancing is difficult to maintain and the risk of infectious disease transmission is increased. In order to reduce this risk, it is essential that we improve our understanding of the dynamics of disease transmission within such places and the effective mitigation measures that can be implemented at low cost. This is the objective of a mathematical model developed by teams from Inserm and Sorbonne Université at the Pierre Louis Institute of Epidemiology and Public Health with the Spanish Institute CSIC-IFISC. Taking the example of London Heathrow airport and diseases such as H1N1 influenza and COVID-19, this model makes it possible to identify zones with the highest risk of transmission within crowded places. By targeting these hotspots with measures such as air filters or the use of Far-UVC lights[1], the scientists also show that it is possible to significantly reduce contamination. Their full findings have been published in Nature Communications.

Crowds and gatherings, with their prolonged contacts between individuals, are a crucial factor in the spread of infectious diseases. While it is possible to implement certain risk reduction measures such as the wearing of masks, the maintenance of social distancing cannot always be respected, especially in transportation hubs such as airports and train stations. After all, these locations are designed to optimize logistical efficiency rather than reduce crowding. They are characterized by a constant in and outflow of visitors, with a high risk of international disease transmission.

The study by the scientists from Inserm, Sorbonne Université and CSIC-IFISC describes a mathematical model that identifies, within these places, the hotspots for the transmission of infectious diseases. It is essential to know exactly where these hotspots are in order to implement appropriate “spatial immunization” strategies, i.e. specific prevention measures that target these zones and reduce contamination.

“In the hotspots that we have identified with our model, the development of dedicated approaches such as air filtration, systematic surface disinfection, and the use of Far-UVC lights can significantly reduce the risk of pathogen spread beyond the first cases arriving at an airport or train station without having been detected,” explains Mattia Mazzoli, Inserm researcher and first author of the study.


A Model Built From GPS Data

In this article, the scientists studied the example of Europe’s busiest airport: London Heathrow. Their model uses anonymized data concerning the movements of over 200 000 people within the airport, derived from the GPS tracking of cell phones between February and August 2017. Using this data, the researchers were able to visualize movements with a spatial resolution of 10 meters, reconstruct the contact networks between these different people, and thereby detect the zones where contacts were the most intense, with a higher risk of contamination.

In order to provide some practical examples, the scientists fed their mathematical model with data concerning the spread of diseases such as H1N1 influenza and COVID-19 in order to study their dissemination throughout the airport.


A Model That Can Be Applied to the Future

The results of this modeling show that the communal areas such as bars and restaurants are where the highest number of infections occur, as these are where travelers and airport staff are brought into contact for long periods of time.

“The danger of these contagion hotspots is driven by a balance between the number of people that use them and the time they spend there. While these are not always the busiest places in the airport, they do involve more sustained contacts for longer periods of time, enabling the spread of diseases,” emphasizes Mazzoli.

Although the model has only been tested with H1N1 influenza and COVID-19, it could still be used in the future to study any new and as yet uncharacterized pathogen. In addition, the method is immediately generalizable to other modes of transport such as trains, subways, bus stations or other crowded facilities where social distancing is impossible, such as malls and convention centers.

“Using spatial immunization measures reduces the number of infections among airport users and, to a lesser extent, among airport staff. When well-targeted and implemented in zones identified as presenting the highest risk, these measures are helpful in containing and/or delaying the spread of infectious agents to the rest of the world via airports or other crowded centers. Our model could be particularly useful in the early stages of a potential future epidemic, when the first cases imported into airports and train stations have not yet been detected,” concludes Mazzoli.

Extreme Temperatures During Pregnancy: A Possible Impact on the Lung Development of Newborn Girls


Exposure to extreme temperatures from the fetal stage could impact health. © Fotalia

Exposure to extreme temperatures from the fetal stage could impact health. This is what suggests a study by researchers from Inserm, Université Grenoble Alpes and CNRS, based on the SEPAGES cohort[1], intended to study the impact of various environmental factors on the health of pregnant women and their children. In this research, to be published in JAMA Network open, associations were found in newborn girls, between in utero exposure to very high or very low ambient temperatures from the second trimester of pregnancy and the alteration of several respiratory parameters.

The thermoregulation implemented by the body in response to variations of temperature requires the adaptation of maternal blood flow and cardiac function which, when this occurs during pregnancy, can be to the detriment of the fetus. Physiological alterations have also been observed in animals in response to heat stress exposures, such as impaired placental development with reduced blood flow, or oxidative stress which, outside of normal conditions, may affect the health of mother and child. External temperature could therefore have an impact on embryo-fetal development.

A team led by Inserm researchers Johanna Lepeule and Ariane Guilbert at the Institute for Advanced Biosciences (Inserm/Université Grenoble Alpes/CNRS), wished to verify this hypothesis using data from the SEPAGES cohort (Assessment of Air Pollution Exposure During Pregnancy and Effect on Health). Made up of pregnant women and children from their pregnancies, this cohort makes it possible to study the effect of various environmental factors on health.


Exposure Modeled Throughout Pregnancy

The researchers modeled the exposure to ambient temperatures of 343 women and their children, from conception to their first weeks of life. At the same time, they evaluated the respiratory function of the newborns at around 6 to 7 weeks after birth. Various measurements were used to calculate the tidal volume (volume of air that enters and leaves with each breath), respiratory rate (number of breaths per minute), and functional residual capacity (FRC) (volume of air remaining in the lungs after an expiration)[2].

Since fetal development and respiratory function differ slightly according to sex, the research team also compared outcomes between girls and boys.


Associations That Vary According to Sex

In boys, the scientists did not observe any significant alterations in lung function associated with external temperature during pregnancy. However, they found that girls exposed in utero from the second trimester of pregnancy to the highest or lowest temperatures had a lower FRC and a higher respiratory rate than those exposed to temperatures closer to the average.

In addition, girls exposed to very low temperatures in utero had decreased tidal volume.

Although the observed variations are not pathological in nature and do not make it possible to predict a future respiratory disorder, explains Lepeule, the various lung function measurements all converge towards an association between in utero exposure to high or low temperatures and poorer lung performance in newborn girls. “

New analyses of the respiratory data collected in children at 3 and 8 years of age will be needed in order to determine whether these associations persist over the long term or whether they are reversible over time.

In the meantime, “these findings underpin the importance of developing public policies to protect pregnant women and their children from extreme temperatures, particularly in the current context of climate change,” concludes Lepeule.


[1] The SEPAGES couple-child cohort (Assessment of Air Pollution Exposure During Pregnancy and Effect on Health), coordinated by Inserm and Université Grenoble Alpes, aims to characterize the exposure of pregnant women and their children to environmental contaminants and study their effect on the health of pregnant women, fetuses, and children.

[2] This residual volume plays an essential role in the maintenance of lung function: as the lungs are elastic, they retract during the muscle relaxation that enables expiration. At the end of expiration, the residual volume makes it possible to limit the retraction forces placed on the lungs so that the pulmonary territories remain open to gas exchange (O2 and CO2 essentially). Otherwise, the lungs would close on themselves, and the alveoli would collapse, meaning that gas exchange could no longer take place.