The race remedies: the 5 main targets of coronavirus

La course aux remèdes: les 5 principales cibles du coronavirus

The coronavirus responsible for the COVID-19 is distinguished from the respiratory virus usual by his versatility which allows him to infect several different bodies and cause serious deficiencies that threaten the life of infected patients. At least five major targets of the virus have been identified so far.

1. The lungs

The respiratory tract is the door of entry of the virus inside the body, these are obviously the lungs are the organs most frequently affected in patients with the COVID-19.

When it manages to infect the cells present in the alveoli of the lung (where the blood is oxygenated), the attack orchestrated by the immune system to kill the virus causes inflammation of strong intensity which causes a local accumulation of fluid and pus that can interfere with gas exchange.

The infection may resolve itself, but if the inflammation goes into overdrive and becomes out of control, damage to lung cells become so important that the patient develops acute respiratory syndrome, and severe, which requires mechanical ventilation.

Autopsy studies have also shown that the inflammation that is uncontrolled due to the formation of multiple blood clots in the lungs(1), which prevents the blood to flow smoothly and contributes to the respiratory distress.

2. The cardiovascular system

These blood clots associated with the COVID-19 are not only found in the lungs, but also affect the overall blood circulation.

The blood vessels and the cells of the heart possess large amounts of the receptor that allows the virus entry to the cell interior (ACE2), and many studies have documented several clinical manifestations of these blood clots, including blood clots and injuries to the lower extremities (the toes, for example). Of cardiac injury severe (myocarditis) have been also reported, and significantly increase the risk of death(2).

This ability of the virus to target particular blood vessels could explain why people who have pre-existing cardiac disease or diseases that affect the health of the blood vessels (diabetes and high blood pressure, for example) are far more likely to develop severe complications from the COVID-19.

3. The nervous system

The blood clots formed in response to the inflammation may also block the blood supply to the brain (STROKE) and cause severe damage that can affect the psychomotor functions.

Damage directly to the nervous system in general have also been described, including a high proportion of patients who develop a loss of sense of smell (anosmia), headache, dizziness, concentration difficulties, or seizures(3).

Guillain-Barré syndrome (attack the peripheral nervous system that can lead to paralysis) has also been reported in patients with the COVID-19.

4. The digestive system

Studies indicate that approximately 15 % of patients infected with the coronavirus develop gastrointestinal symptoms such as diarrhea, nausea, and vomiting.

The RNA of the virus is present in feces of half of the infected patients, suggesting a possible route of transmission fecal-oral.

The studies performed on organoids of intestinal (small intestines grown in the laboratory) indicate that the sars coronavirus is capable of infecting directly the intestinal cells (enterocytes) due to the very strong expression of the receptor ACE2 on the surface of these cells(4).

5. The pancreas

The study of organoids pancreas indicates that the coronavirus can also infect and destroy cells of the pancreatic islets responsible for insulin production(5).

This property would explain why some hiv-infected patients present at the time of hospitalization of the classic signs of type 1 diabetes, including hyperglycemia and diabetic ketoacidosis (excess ketones).

There is therefore an association is bidirectional between the diabetes and the COVID-19 : on the one hand, people with diabetes are at very high risk of developing severe forms of the disease ; on the other hand, the infection by the coronavirus can affect the production of insulin and cause the disorders of metabolism typically found in people with diabetes.

CONCLUSION

Overall, the clinical characteristics of the COVID-19 highlight well the extent of tissue damage caused by the coronavirus SARS-CoV-2 and underscore the importance of find in the shortest time possible new therapeutic interventions against this disease. Fortunately, the tremendous progress made over the last few months in the development of a vaccine, as well as the identification of neutralizing monoclonal antibodies allow us to view with optimism the imminent arrival of an effective treatment against the COVID-19.

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

(2) Guo T et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol., published on 27 march 2020.

(3) Pleasure SJ et al. The spectrum of neurologic disease in the severe acute respiratory syndrome coronavirus 2 pandemic infection: neurologists move to the frontlines. JAMA Neurol., published on April 10, 2020.

(4) Lamers MM, et al. SARS-CoV-2 productively made you sick human gut enterocytes. Science 2020 ; 369 : 50-54.

(5) Yang L et al. A human pluripotent stem cell-based platform to study SARS-CoV-2 tropism and model virus infection in human cells and organoids. Cell Stem Cell 2020 ; 27 : 125-136.

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