Covid-19: Avenues to understand why obesity is a risk factor

After a year and a half of the Covid-19 pandemic, scientific research has had time to investigate the disease and the specificities of its development. After age, theobesity is now considered the second risk factor for hospitalization following infection with the SARS-CoV-2 virus.

Since the link between obesity and respiratory diseases has already been established, for example for sleep apnea, this correlation did not particularly surprise us.

Nevertheless, questions remain to explain the mechanisms involved and in particular as to the role of adipose tissue in the severity of the disease.

Since the start of the epidemic, data has been accumulating to show that among patients with Covid, around 5% are hospitalized in intensive care due to the runaway of their immune system associated with an overreaction of inflammatory disease. This is the famous "cytokine storm".

Obese patients seem to be particularly vulnerable to it. To improve care and identify suitable treatments, it is essential to understand why, and to identify which biological and immunological characteristics are involved in this phenomenon.

The role of adipose tissue

Obesity is not just about having a high body mass index (BMI) - that is, weight divided by height squared, equal to or greater than 30kg / m² >. It is also characterized by an excess of adipose tissue (all the cells that store fat, or adipocytes). In addition, people with a high BMI have persistent signs of inflammation associated with the production of metabolic residues by adipose tissue that some immune cells identify as “danger signals”.

Because of this pre-existing inflammation, several research teams had hypothesized that these patients would be at greater risk of developing a severe form of the disease. The pulmonary infection by SARS-CoV-2 would thus worsen the pre-existing inflammation, creating greater damage to the lungs and spreading in the most severe cases to other organs.

Still under study, however, this lead does not explain why such inflammation is not observed to a similar degree in obese people during infections with other coronaviruses, such as MERS-CoV or SARS-CoV. . It is therefore essential to continue investigations to determine what are the particularities of SARS-CoV-2 that lead to such a runaway immune system in obesity.

Infection and inflammation

Another line of research emerges: upon infection with the SARS-CoV-2 virus, the immune system's response leads to an influx of pro-inflammatory cytokines - small proteins secreted by immune cells, and which help guide our defense. The interactions between cytokines and adipocytes in adipose tissue would be responsible for the excessive inflammation observed.

Stimulated by these cytokines, adipocytes will also activate the degradation pathways of the lipids they store, which leads to the release of large amounts of fatty acids in the body. This alteration in lipid metabolism would accentuate inflammatory processes and contribute to the destruction of cells in certain organs.

It should also be noted here that male obesity promotes an accumulation of adipose tissue in the visceral cavity and therefore near vital organs. Which could partly explain the greater severity of Covid-19 infections in men compared to women.

Other avenues to explore

It is also necessary to continue work on the role of the ACE2 receptor. Present on the surface of different cell types, the latter plays a key role with the SARS-CoV-2 responsible for Covid-19 since it is he who allows entry of this virus into the host's cells. However, many ACE2 receptors are present on the surface of adipocytes, therefore making this tissue a potential reservoir for viral replication. With a higher number of adipocytes, obese people also have a larger surface area of ​​cells that can be infected.

In addition, it may be of interest to study the body's Renin-Angiotensin-Aldosterone hormonal system, which plays an essential physiological role in cardiac, renal and blood pressure regulation. Many players in this system are found in adipose tissue, and could establish a link with hypertension, which is another risk factor for the severity of Covid-19 disease.

Finally, it should be remembered that the lipids stored by adipocytes play a key role in the life cycle of viruses: in particular they provide the energy necessary for viral replication, but also play a crucial role in the entry of the virus into the virus. the infected cell, as in the release of new viral particles.

The understanding of these mechanisms is yet to be deepened, but it is likely that they partly explain the severity of the infection in obese patients.

Prospects and therapeutic research

As our knowledge of this new disease progresses, we realize the diversity and complexity of the symptoms. These seem to establish a clear link between the severity of the Covid-19 infection and the pre-existence of various risk factors, among which obesity is today one of the best validated. However, highlighting the possible links between these different risk factors now requires optimal stratification of all Covid-19 patients. In other words, it is necessary that all the physiological and clinical parameters for each patient can be referenced in order to allow a detailed analysis.

Research teams are already working on the basis of these hypotheses to develop new treatments, in particular molecules targeting the ACE2 receptor and capable of blocking the entry of the virus into cells. Pending promising results, lifestyle interventions to limit obesity-related problems could be considered. For example, several studies have highlighted the benefit of a Mediterranean diet and regular physical activity in reducing the signs of chronic inflammation in obese people over the longer term.

Beyond this work, it will also be essential to offer adequate follow-up to these patients, in order to understand whether they are also at greater risk of sequelae.

Nicolas vitale, Director of recherche, Inserm

This article is republished from The Conversation under Creative Commons license. Read theoriginal article.