The race for cures: portrait-robot of a virus that is very special

La course aux remèdes: portrait-robot d’un virus très particulier

In the last six months, the international scientific community has made tremendous progress in the understanding of the molecular characteristics of the coronavirus responsible of the COVID-19, and the impacts of this disease on the human body. The conclusion is implacable : it is really a respiratory virus very particular, that obliges us to rethink our approach to the prevention and treatment of this disease. Take advantage of the monthly balance sheet of the research to make the point.

5 signatures of the coronavirus

The severity of the COVID-19 varies enormously from one person to another. In many cases, the infection is silent (asymptomatic), or produces minor symptoms, while in others, the disease progresses quickly to forms a very severe which requires hospitalization and may lead to death.

At least five features of coronavirus are responsible for these interindividual differences, and these characteristics of the virus can be considered as unique signatures to this infectious agent.

1 | Discrimination based on age

According to data collected by the INSPQ (10 June 2020), of people aged 70 years and over account for 92 % of 5105 deaths caused by the COVID-19, and this, despite the fact that this age group constitutes only 13 % of the quebec population.

  • The elderly are clearly at much greater risk of developing serious complications of the COVID-19.
  • According to a british study, a person over 80 years old, has 12 times the risk of dying from the disease compared to a person of 50 years1.

The gradual decrease of the efficiency of the immune system during aging contributes certainly to the greater vulnerability of older people to the virus.

It is essential to rethink our approach to take account of this reality and put in place more effective preventive action to protect this vulnerable population in the event of a resurgence of the virus in the coming months.

2 | sex Discrimination

If men and women have the same probability of being infected by the coronavirus, several studies have reported that men develop more frequently from severe forms of the disease, and are about two times more at risk of décès2.

A similar phenomenon is observed in Quebec, where the men represent only 35 % of the population of persons aged 80 years and older, but account nevertheless for 45 % of deaths.

  • Studies suggest that this difference in severity between the two sexes could be related to sex hormones, the estrogen women have a protective effect, whereas the male androgen could promote the infection by the coronavirus.
  • The medicines antiandrogen, such as those used for the treatment of prostate cancer, may represent a therapeutic avenue to be interesting to reduce this gap man-femme3.

3 | Discrimination according to the health

The majority of patients who develop severe forms of the COVID-19 are chronic conditions pre-existing at the time of infection, the most common being hypertension, cardiovascular disease, and type 2 diabetes.

These diseases increase by 5 to 10 times the mortality risk compared to people who did not have pre-existing conditions, as shown by the predominance of deaths in NURSING homes, with a population of patients to health is already very poor.

  • It seems, therefore, that the metabolic disturbances caused by these diseases will create fertile ground for the coronavirus and amplify its virulence.
  • Therefore, it is essential to master as far as possible these existing conditions to reduce the risk of further aggravation of the COVID-19.

In this sense, it should be noted that in diabetics, optimal control of blood glucose is associated with a very significant decrease (10-fold) the risk of serious complications from the COVID-19 observed in diabetic patients whose blood sugar is too élevée4.

4 | Discrimination according to the weight

Several studies have reported that young adults (under 60 years) who were overweight were more at risk of developing severe forms of COVID-19.

Several factors account for this link between obesity and complications of COVID :

  1. The excess fat creates a climate of chronic inflammation that favors the appearance of metabolic abnormalities (hypertension, hyperglycemia, dyslipidemia) that are known to promote the evolution of the COVID-19 to severe forms.
  2. This inflammation disrupts the effectiveness of the immune system and therefore promotes infection.
  3. Excess fat, especially if it is present at the level of the abdomen impairs breathing by restricting the movement of the diaphragm and promotes at the same time a faster deterioration of lung function and the risk of death.

From a therapeutic point of view, the important contribution of chronic inflammation to the complications observed in the obese suggests that many anti-inflammatory agents that are currently in the study could represent a treatment approach interesting for use in this population.

5 | Attack of the blood vessels

In addition to affect preferentially certain populations, another signature very particular coronavirus is its ability to directly attack the cells that line blood vessels (endothelium).

The receptor ACE2, which allows the entry of the coronavirus SARS-CoV-2 in the cells, is very abundant on the surface of endothelial cells and a recent study has shown the presence of multiple viruses in the blood vessels, as well as many of the damage affecting the structure of these cellules5.

These damage inflicted on cells by the virus makes vessels that are very permeable, an injury that causes an activation of the coagulation process, the formation of blood clots (thrombosis) and inflammatory cell recruitment.

This inflammatory response may then get carried away and generate a storm of cytokines, is a hyper-inflammation which destroys the surrounding tissue and compromises organ function.

  • Since people with diabetes and with cardiovascular disease already show abnormalities in their blood vessels at the time of infection, this mechanism could explain the higher susceptibility of these individuals to develop severe forms of COVID-196.
  • The use of anti-inflammatory medications such as colchicine or antibodies developed against inflammatory cytokines (TNF and interleukin-6) could attenuate this inflammatory response is disproportionate and, therefore, prevent the development of serious complications of infection in these high-risk people.

Enemy versatile

In sum, the more one progresses in this war, the sars coronavirus, the more one realizes that one is facing an enemy versatile, capable of causing considerable damage not only the lungs, but also to a number of other vital organs (heart, kidney, brain).

The elderly and already sick people are prime targets of this virus and it is absolutely necessary to adapt our societal response to take account of this fact, by prioritizing the protection of these more vulnerable people.

Take advantage of the discoveries

From the therapeutic point of view, we must of course hope for the development of a vaccine in the near future, but until then, you can take advantage of the latest discoveries and continue to test new drugs that can mitigate the effects caused by the virus, in particular everything related to the dysregulation of the inflammatory response and coagulation disorders.

The recent discovery that dexamethasone, an anti-inflammatory steroid used clinically for several years, significantly reduces the mortality of critically ill patients by the COVID-19 is a good example of the importance of this approach.

Sources :

1. The OpenSAFELY Collaborative. OpenSAFELY: factors associated with COVID-19 — related hospital death in the linked electronic health records of 17 million adult NHS patients. medRixv, submitted on may 7, 2020.

2. Jin JM et al. Gender differences in patients with COVID-19: focus on severity and mortality. Front. Public Health. 2020; 8: 152.

3. Wambier CG, and Goren. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is likely to be androgen mediated. J. Am. Acad. Dermatol. 2020; 83: 308-309.

4. Zhu L et al. Association of blood glucose control and outcomes in patients with COVID-19 and pre-existing type 2 diabetes. Cell Metabolism In 2020; 31:1068-1077.

5. Ackermann M et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in COVID-19. N. Engl. J. Med., published may 21, 2020.

6. Matacic C. Blood vessel attack could trigger coronavirus fatal “second phase”. Science, published on 2 June 2020.

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