COVID-19 Causes 3 Times More Deaths Than Seasonal Flu

SARS-CoV-2 coronavirus attached to the cilia of human respiratory epithelial cells.© Manuel Rosa-Calatrava, INSERM ; Olivier Terrier, CNRS ; Andrés Pizzorno, Signia Therapeutics ; Elisabeth Errazuriz-Cerda UCBL1 CIQLE. VirPath (Centre International de Recherche en Infectiologie U1111 Inserm – UMR 5308 CNRS – ENS Lyon – UCBL1). Colorized par Noa Rosa C.


A study by Inserm and Dijon University Hospital based on French nationwide data on around 130,000 patients hospitalized for either COVID-19 or seasonal influenza shows that the mortality rate among those admitted for COVID is three times higher than that of seasonal influenza. These findings have been published in The Lancet Respiratory Medicine

This study uses data from the French national administrative database (medicalized information system program – PMSI), which contains information on all patients admitted to public and private hospitals in France, such as the reasons for their admission and the treatment they received. The researchers compared the admissions for COVID-19 (between March 1 and April 30, 2020) with those for seasonal influenza (between December 1, 2018 and February 28, 2019).


The results reveal:


  • A mortality rate among the patients hospitalized for COVID-19 three times higher than that of those admitted for seasonal influenza. Of the 89,530 patients admitted for COVID, 15,104 [16.9%] died versus 2,640 [5.8%] of the 45,819 patients hospitalized for influenza.


  • More COVID-19 patients required admission to intensive care with an average stay that was almost twice as long (15 days versus 8 days).


  • Fewer children under 18 years of age were hospitalized for COVID-19 than for seasonal influenza, but a larger proportion of the patients younger than 5 years needed intensive care support for COVID (14 out of 613) than for influenza (65 out of 6973). The mortality rate for the children under 5 years of age was similar for both groups and very low (less than 0.5%).


  • Almost twice as many people were hospitalized for COVID-19 at the peak of the pandemic compared to those who had been hospitalized for influenza at the peak of its 2018/2019 season.


  • In addition, a larger proportion of the COVID-19 patients had a severe form of the illness requiring intensive care than those with influenza. Looking at the number of admissions to intensive care: out of the 89,530 COVID-19 patients, 14,585 [16.3%] were admitted to intensive care versus 4,926 [10.8%] of the 45,819 influenza patients.


  • More than one in four COVID-19 patients suffered from acute respiratory failure, versus fewer than one in five with influenza.


  • Consistent with previous reports, the most common underlying medical conditions among the patients admitted with COVID-19 were hypertension (33.1%), overweight or obesity (11.3%), and diabetes (19.0%).

The researchers point out that their study has several limitations. In particular, testing practices for influenza are likely to be highly variable across hospitals, whereas practices for COVID-19 may be more standardized. This may partly explain the increased number of admissions for COVID-19 compared to seasonal influenza. In addition, the difference in hospitalization rates may be partly due to existing immunity to influenza in the population, either from previous infection or vaccination.

Nevertheless, the conclusions of this research confirm the importance of measures to prevent the spread of both diseases. Measures that are particularly relevant at a time when several countries are preparing for the COVID-19 pandemic to continue in parallel with seasonal influenza outbreaks during the winter months.

“This study is the largest to date comparing the two diseases and confirms that COVID-19 is much more serious than influenza. The finding that the COVID-19 death rate was three times higher than that of seasonal influenza is particularly striking when one recalls that in the last five years the 2018/2019 influenza season has been the worst in France in terms of number of deaths,” declares Catherine Quantin, researcher at Inserm and Professor at Dijon University Hospital.

“Taken together, these findings clearly indicate that COVID-19 is much more severe than seasonal flu. While no treatment has yet been shown to be effective in preventing serious illness in COVID-19 patients, this study underlines the importance of the various prevention measures (barrier measures) and highlights the need for access to effective vaccines,” concludes Pascale Tubert-Bitter, research director at Inserm.

Discovery of a Mechanism Explaining the Beneficial Action of Cancer Drug Tamoxifen on the Cardiovascular System

Image showing the endothelial healing process in mice 3 days following carotid artery injury. © Coralie Fontaine.

A commonly used treatment in some forms of breast cancer, tamoxifen acts on the cancer cells by blocking the estrogen receptor (ER)a and thereby inhibiting their proliferation. However, the action of this drug appears to be more complex than that, with the addition of protective effects on the arteries that could reduce the risk of developing cardiovascular disease. Researchers from Inserm and Université Toulouse III – Paul Sabatier at the Institute of Cardiovascular and Metabolic Diseases have studied the effects of tamoxifen on the arteries in animal models in order to better understand its mechanism of action and refine its clinical use. Their findings have been published in the journal Circulation Research.

Following breast cancer, women are at increased risk of developing cardiovascular disease. Several studies have confirmed this association, highlighting risk factors common to both disease types as well as the toxicity of certain cancer treatments, such as chemotherapies, to the cardiovascular system. However, experimental and clinical data suggest that tamoxifen – a hormone therapy that reduces the risk of recurrence of certain forms of breast cancer[1] – also has protective effects against cardiovascular disease.

In the cancer cells, tamoxifen acts as an anti-estrogen: without eradicating the production of this hormone, it takes its place in its receptors (the ERa receptors), thereby blocking the proliferation of these cells.

However, the action of this drug is not limited to blocking the estrogen receptors of the cancer cells. In other cell types it could have the opposite effect of activating these same receptors, as estrogens do.

Different mechanisms of action

In their study, the researchers have shown that tamoxifen accelerates arterial healing by promoting the renewal of the endothelial cell layer that protects the arteries, thereby revealing a novel beneficial effect of this drug in terms of cardiovascular risk.

In order to explain this novel beneficial action of tamoxifen, the team shows that contrary to its inhibiting effect on the cancer cells, the drug mimics the action of the estrogens in the arteries, bringing about their healing.

However, the cellular mechanisms involved are thought to be different.

Whereas estradiol (the main estrogen) induces this effect by directly activating the estrogen receptors in the arterial endothelial cells, the researchers show that tamoxifen produces this same effect on the arteries by also activating the estrogen receptors, but in another cell type (the underlying smooth muscle cells).

This research therefore shines a new light on the action of tamoxifen, showing that this molecule can mimic the action of estrogens by targeting the different functions of their receptors in different cell types.

These findings could have various clinical implications, particularly because they enable a deeper understanding of the spectrum of action of this drug that is prescribed to thousands of patients in oncology.

They are also expected to generate further research on this molecule that has been in use for 40 years.

“The vision we have of tamoxifen at present is that of a hormone therapy that blocks the receptors present on the cancer cells, but this only partially explains its action. Our study emphasizes that this drug mimics estrogens by targeting pathways that are not always the ones we expect. We have revealed a protective effect on the arteries through an indirect action on the endothelial cells, but this action could also affect the immune system cells, which play a key role in the immune surveillance of tumors”, emphasize Jean-François Arnal, professor at Université Toulouse III – Paul Sabatier, and Coralie Fontaine, Inserm researcher, who have coordinated this research.


[1]So-called “hormone-dependent” cancers, for which the cancer cells express the estrogen receptor

Study – Particularly active antibodies to act as a barrier to SARS-CoV-2

Colorized image of human bronchial cells (blue) infected with SARS-CoV-2 virus (orange). © Institut Pasteur. Image by Rémy Robinot, Mathieu Hubert, Vincent Michel, Olivier Schwartz & Lisa Chakrabarti, colors by Jean Marc Panaud

Teams from the Pitié-Salpêtrière AP-HP hospital, Sorbonne University, Inserm and the Pasteur Institute have carried out work to study the role that IgA-type antibodies play in the protection of body against Covid-19 in the mucous membranes, in particular respiratory. This work in press in Science Translational Medicine , and which is the subject of a pre-publication on Monday, December 7, 2020 on the website of the journal Science Translational Medicine , shows that the IgA antibody response plays a key role in neutralizing the early and particularly effective SARS-CoV-2 virus.

IgA-type antibodies play an essential role in the protection of the organism at the level of the mucous membranes, in particular respiratory. It therefore made sense to study this particular antibody response in patients infected with the SARS-CoV-2 virus. Researchers and clinicians affiliated with the CIMI Research Center (Sorbonne University and Inserm) in collaboration with several clinical departments of APHP-Sorbonne University and teams from the Institut Pasteur, show that the IgA response plays a key role in neutralizing the early and particularly effective SARS-CoV-2 virus.

Somewhat surprisingly, IgA antibodies are often even the first detectable virus specific antibodies. An unusual profile since immunological dogma wants the IgM response to be dominant when encountered with an unknown pathogen. The stimulation induced by the virus induces a very large expansion of young cells secreting IgA antibodies (plasmablasts) which circulate between the blood and the mucous membranes in which they are able to reside. However, this IgA antibody response is slowly declining, including in the saliva.

The teams in charge of this work show that in the first weeks following infection, IgA type antibodies do most of the work of neutralizing the virus.

The level of these antibodies decreases rapidly in the blood, becoming weakly detectable in most people 30 days after the onset of symptoms. However, these antibodies remain detectable and active in saliva longer (up to 73 days after the onset of symptoms) even though this level of local protection also seems to decline slowly. In a subgroup of patients having presented a mild ambulatory form, it is indeed reported that approximately 6 months after the counting, saliva no longer exerts a neutralizing power on the virus.

In conclusion, this work highlights the powerful protective nature of IgA. It raises the question of the possible role of secretory IgA in limiting the transmission of the virus.

It will therefore be interesting to assess to what extent the various vaccines which will soon be widely available could induce, or not, a systemic IgA response, or even mucosal.

If necessary, it may be considered to eventually include local stimulation in our vaccine strategies, for example in the form of local nebulizations.

Published Now in the New England Journal of Medicine: The Initial Results of the Solidarity/Discovery Clinical Trial

©Adobe Stock

Back at the start of the pandemic, Inserm, through its REACTing consortium, set up Discovery: a European clinical trial to evaluate the efficacy of four antiviral drugs repurposed for the treatment of patients hospitalized with COVID-19 (remdesivir, hydroxychloroquine, lopinavir and interferon beta-1a). In parallel, the World Health Organization (WHO) set up Solidarity, a major consortium of clinical trials also aimed at testing the efficacy of these four treatments. Discovery then joined forces with Solidarity to help supply it with robust and rigorous data. The initial results of Solidarity have now been published in the New England Journal of Medicine.

Launched in March 2020 under the aegis of Solidarity – the World Health Organization (WHO) global clinical trials – Discovery is a clinical trial to study efficacy and safety. It is the only large-scale European academic trial of COVID-19 treatments.

Focusing on patients hospitalized with severe COVID-19 in France and other European countries, this trial is both randomized (the treatments are randomly assigned to the participants) and open-label (the patients and their caregivers know which treatment they have been allocated). The data obtained in Discovery form part of the data analyzed within the framework of Solidarity and have been presented in the study by the New England Journal of Medicine.

The analysis covers 11,330 adult patients in 405 hospitals across 30 countries and includes Solidarity’s “daughter trials” (with one of the main contributors being Discovery). The patients were assigned to different groups in order to receive one of the following regimens:

  • Remdesivir + standard of care
  • Hydroxychloroquine + standard of care
  • Lopinavir + standard of care
  • Interferon (or interferon and lopinavir) + standard of care
  • Standard of care that is given to all patients hospitalized with severe COVID-19

The results suggest that none of these treatments have an effect on the clinical improvement of patients. None of them significantly reduce overall mortality, the risk of having to initiate mechanical ventilation, or the duration of hospitalization.

However, within the framework of Solidarity and Discovery, it has nevertheless been decided to continue enrolments in the remdesivir group. Indeed, the meta-analysis presented in the study suggests that although mortality is not reduced in the mechanically ventilated patients in intensive care having received remdesivir, it does show that remdesivir may slightly reduce mortality in the subgroup of hospitalized patients who do not require mechanical ventilation. In addition, while a scientific consensus is emerging as to the lack of efficacy of the other therapeutic combinations tested in Solidarity, data published in other studies remain contradictory on the subject of remdesivir.

The decision by the Discovery investigators to continue enrolments in this group has therefore been made with the aim of obtaining new data in order to decide one way or the other on the utility of remdesivir in severe COVID-19.

Discovery has received funding from the European Commission and is currently enrolling patients hospitalized for severe COVID-19 in five European countries (other European countries will soon follow and are awaiting regulatory approvals).

A Disruption of the Microbiota Is Linked to the Formation of a Molecule Promoting Type 2 Diabetes

Diet plays a major role in the composition of our gut microbiota. From what we consume, the gut bacteria produce organic compounds known as metabolites, which can affect our health. © Adobe Stock

An imbalanced diet has been linked to a disruption of the gut microbiota, which promotes metabolic diseases such as diabetes. Researchers from Inserm, Sorbonne Université, Paris hospitals group AP-HP and the French National Research Institute for Agriculture, Food and Environment (INRAE) in collaboration with a Swedish team have shown, in a large European cohort, that changes in the composition of the gut microbiota lead to increased blood levels of the molecule imidazole propionate. A molecule known to render the body’s cells resistant to insulin, thereby increasing the risk of developing type 2 diabetes. Their findings have been published in Nature Communications.

Diet plays a major role in the composition of our gut microbiota. From what we consume, the gut bacteria produce organic compounds known as metabolites, which can affect our health if they are present in too large or too small a quantity in our body.

Previous studies have shown that changes in the makeup of the gut microbiota and the production of certain metabolites can directly influence the development of type 2 diabetes.

For example, they have revealed that lower levels of the bacteria that produce butyrate, a fatty acid known to improve insulin sensitivity, are linked to an increased risk of diabetes.

Other recent research suggests that an alteration of the gut microbiota disrupts the metabolism of histidine, an amino acid found in many foods, leading to increased levels of the metabolite imidazole propionate. This molecule blocks the action of insulin, preventing it from lowering blood glucose levels.

The present study published in Nature Communications confirms these initial findings in a large European cohort of 1990 participants from France, Germany and Denmark, called METACARDIS. Coordinated by Inserm, the objective of this cohort is to study the impact of changes in the gut microbiota on the onset and progression of cardiometabolic diseases and associated pathologies. “METACARDIS is a unique and valuable database in that it allows us to access very detailed characteristics of each person enrolled in the cohort with large amounts of phenotypic, metabolic, and bacterial genetic data,” emphasizes the project’s coordinator, physician Karine Clément, teacher-researcher in nutrition at Sorbonne Université.

She and her colleagues show that in the cohort, subjects with prediabetes[1] or type 2 diabetes do indeed have higher levels of imidazole propionate in their blood. The gut microbiota of these subjects is also characterized by a significant depletion of bacteria.

The researchers suggest that these alterations in the bacterial composition of the microbiota are linked to an imbalanced diet. They cause a disruption in the metabolism of histidine, which in turn leads to an increase in imidazole propionate and problems regulating blood glucose. The risk of developing type 2 diabetes then becomes higher.

“Our study suggests that people with poor diets have increased levels of imidazole propionate and that there is a clear link between the depleted composition of the microbiota, diet and type 2 diabetes. Its aim is to convey a message of prevention, emphasizing that a more varied diet can enrich the microbiota. This study also has therapeutic implications since we could envisage the future development of drugs to modify the synthesis of certain metabolites such as imidazole propionate,” explains Clément.

A number of questions continue to be raised and are expected to be elucidated in future research based on METACARDIS. In particular, the researchers want to understand how the elevation of one or more metabolites can predict, in people with diabetes, the risk of developing other complications, such as those affecting the cardiovascular system. They also want to study how increased imidazole propionate levels in people with prediabetes could increase their risk of developing type 2 diabetes earlier on in their clinical course.


This large-scale research project, based on close collaboration between several European scientific teams, has received support from the European Community (7th Framework Programme FP7-Metacardis), as well as from the Leducq Foundation.

[1] Prediabetes is a blood glucose disorder at a less advanced stage than diabetes itself. It is characterized by fasting blood glucose levels of between 1.10 g/L and 1.25 g/L (normal fasting blood glucose is below 1.10 g/L). The risk of going on to develop type 2 diabetes is increased.

Deciphering the energetic code of cells for better anticancer therapies







© Olivier Cabaud

A procedure that may help personalise anticancer therapies has just been developed by the CNRS, Inserm, and Aix-Marseille University scientists at the Centre d’Immunologie de Marseille-Luminy, in association with colleagues from the University of California San Francisco and the Marseille Public University Hospital System (AP-HM), with support from Canceropôle Provence–Alpes–Côte d’Azur. Their patented technique1 reveals the energy status of cells, an indicator of their activity. It is presented in Cell Metabolism (1 December 2020).

Immunotherapies are a promising anticancer arsenal and work by mobilizing the immune system to recognize and destroy cancer cells.2 Currently, however, only a third of patients respond to immunotherapies: the tumour environment can be hostile to immune cells, depriving them of their source of energy, which diminishes treatment efficacy. The energy status of the various types of immune cells is a marker of their activity, and particularly of their pro- or antitumour action. To boost the effectiveness of immunotherapies, it is thus essential to have a simple method for characterising the energy profiles of immune cells from tumour samples.

SCENITH1 is just such a method. Developed by scientists working in Marseille and San Francisco, it identifies energy sources on which the different cells in the tumour are dependent and, most importantly, the specific needs of immune cells in this hostile environment.

It uses the level of protein synthesis, a process responsible for half of cellular energy consumption, as an indicator of a cell’s energy status. The biopsy sample is separated into subsamples that are each treated with an inhibitor of a metabolic pathway through which cells produce energy. Levels of protein synthesis are then measured using a flow cytometer,3 which also makes it possible to differentiate types of cells in the sample and identify cell surface markers targeted by therapies. The SCENITH method thus identifies the energy status of each immune or cancer cell within the tumour, its energy sources, and the metabolic pathways it relies upon.

The scientists behind SCENITH have already begun working with clinical research teams to better understand how it might be used to predict patient treatment response.4 They seek further collaborations of this kind to determine profiles associated with different responses to immuno- and chemotherapy. SCENITH seeks to enable personalised treatment for each patient that exploits the strengths of the immune response and the weaknesses of the tumour.


  1. SCENITH: Single Cell ENergetIc metabolism by profilIng Translation inhibition. Patent: PCT/EP2020/060486
  2. The 2018 Nobel Prize in Physiology or Medicine was awarded for the discovery of immunotherapeutic mechanisms. Find out more about immunotherapy:
  3. A flow cytometer is an apparatus that can be used to evaluate each sample cell’s size or shape, or any other cell component or function affecting the intensity of the fluorescent stains employed.
  4. Lopes N, et al. Metabolism and function of γδ T cell subsets in the tumour microenvironment. Nature Immunology (In press).

The SCENITH project received support from Canceropôle Provence–Alpes–Côte d’Azur, the French National Cancer Institute (INCa), France’s Sud regional authority, and INSERM Transfert.

Find out more:

Neuroscience Provides New Ways to Understand the Origin of Our Emotions

Emotions have long been considered as innate and universal biological experiences, quite distinct from each other. ©Adobe Stock

Are our emotions innate or are they the product of our culture and environment? This question has long been the subject of debate in the field of neuroscience. Researchers from Inserm, Université de Caen Normandie, Ecole Pratique des Hautes Etudes and the University Hospitals of Caen and Rennes provide robust clinical data in favor of the second hypothesis. Their work suggests that our ability to know and recognize emotions is built up gradually and depends on our knowledge of language. Their findings have been published in the journal Brain.

Throughout the history of neuroscience, the question of the origin of emotions has always intrigued scientists. Based on Charles Darwin’s theories, they have long considered emotional states as innate and universal biological experiences, quite distinct from each other.

Faced with the observation that emotions are not defined in the same way in all cultures, and that the boundaries between the categories (joy, sadness, anger, etc.) are not the same throughout the world, this viewpoint has nevertheless continued to evolve. A so-called “constructionist” hypothesis of emotions has thus developed over recent decades, postulating that emotions are not innate but rather concepts learned in childhood and associated with our physical sensations.

These concepts would be enriched throughout life, according to our experiences and environment. However, robust data from brain imaging and clinical practice were lacking to confirm this theory.

To decide between the two schools of thought, Inserm researcher Maxime Bertoux and the team of the Neuropsychology and Imaging of Human Memory laboratory (Inserm/Université de Caen Normandie/École Pratique des Hautes Etudes) in association with the University Hospitals of Caen and Rennes and GIP Cyceron studied 16 patients suffering from a rare neurodegenerative disease, known as “semantic dementia”.

This disease is characterized by a degradation of conceptual memory, i.e. a loss of knowledge about the world and language. “Patients have difficulty mobilizing what they have learned throughout their lives, for example, remembering that Paris is the capital of France. They are also unable to identify everyday objects and remember how they work or what they are used for, or understand the meaning of words. However, the degradation of conceptual knowledge associated with this disease should not impact patients’ ability to know and recognize emotions, if they are truly innate,” explains Bertoux.

Brain network identified

The participants were tested on their conceptual knowledge of four emotions: anger, pride, surprise and embarrassment. As part of the first step, they were asked to give a synonym for each of these emotions and then choose another similar word from a list. They were then asked to give an example of a context in which this emotion could be felt and then, from a list of situations, choose the one most likely to cause the emotional state in question. As part of the second step, the participants watched photos and videos of actors expressing emotions. They then had to recognize which emotion was represented.

Compared to the healthy participants, the conceptual memory of emotions was more impaired in the participants with semantic dementia. On average, these patients were, for example, less able to give or choose the correct synonym for a particular emotion, and also less able to select the appropriate context in which to expect to feel it. They also had greater difficulty recognizing emotional states expressed by others, whether positive or negative, presented in photographs or videos.

Based on these findings, the researchers reveal a strong correlation between the loss of conceptual knowledge memory and the difficulty in recognizing emotions and their positive or negative nature.

The researchers also used brain imaging techniques to identify the brain networks mobilized during the performance of these various exercises. Their results suggest that the same network is at work in both the tasks of recognizing facial emotions and those of mobilizing conceptual knowledge about emotions.

“Our study highlights the strong link between “affective” neurocognitive processes, linked to the recognition of emotions, and “conceptual” processes that were supposedly distinct. We show that our conceptual and linguistic knowledge play a decisive role in how we perceive emotions. This enables us to supply new elements to confirm the constructionist theory of emotions: that we culturally construct our emotions from childhood,” emphasizes Bertoux.

This work is also of interest in the clinical field. Indeed, many psychiatric and neurodegenerative diseases cause emotional disturbances.

“Our study supports the utility of cognitive, behavioral and emotional approaches in mental illness and neuroatypical states. Recognizing an emotion in others but also regulating our own emotions depends on our ability to have learned to name them and distinguish them conceptually,” concludes Bertoux.