The immune system and COVID-19: how it works

Why do some people suffer from acute respiratory distress, while others have no symptoms? Do seniors die so often because their immune system is too weak? The answer isn’t simple. That’s because the immune system involves a wide variety of mechanisms that can largely be separated into 3 lines of defence. 
The first line of defence: physical and chemical barriers 

No virus can multiply on its own. First it must attach itself to a cell, insert its genome and force the cell to make copies of itself. This takeover isn’t always successful. The virus entering the airway or digestive tract encounters a first line of defence, composed of mucus and epithelial cells, which line the interior of the mouth and nose (physical barriers). It also encounters chemical barriers, in the form of mucus, saliva, tears and gastric juices. The epithelial cells of the airway have small hairs that push out foreign objects.  

What makes the COVID coronavirus so contagious are its surface proteins. They specifically align with the ACE2 receptors present on the membrane of these epithelial cells that are supposed to protect us. If enough viruses are introduced by breathing, some will break through the first line of defence. They will attach themselves to this cell membrane and insert their RNA. That’s when the infection begins.  



The second line of defence: innate immunity 

The second line of defence then comes into play to prevent this proliferation, or at least control it. It calls on the different types of white blood cells that work together. Macrophages and neutrophils, for example, will recognize and “swallow up” viruses.  

Dendritic cells will isolate the surface proteins of viruses (the “antigens”) and present them to the T lymphocytes. The T lymphocytes can adapt specifically to these viral antigens and destroy countless mass-produced viruses.  

At the same time, natural killer (NK) cells will attack not the viruses but the epithelial cells they pirated and that then became virus factories.  

In this war against intruders, the many cells of the innate immune system also produce a wide range of proteins (histamine, proteases, prostaglandins, heparin, cytokines, interferon, growth factors, complement proteins). These proteins play multiple roles to eliminate viruses.  

For example, vasodilators will allow the blood vessels to bring more blood and white blood cells to the attack site. Growth factors will accelerate renewal of the epithelial cells to replace the infected cells destroyed by the natural killer (NK) cells. Cytokines will act as messengers to mobilize white cell reinforcements at the infection site. Cytokines also activate the cells responsible for “cleaning out” intruders, or they inhibit viral replication within the cells.  

All this generates intense activity on the cellular battlefield. This is called inflammation. It leaves behind dead bodies and debris. The body will react by trying to expel this waste. These are classical diseases symptoms: fever, increase in mucus production, runny nose, cough, sore throat…  

When viruses penetrate the pulmonary alveoli, inflammation, cell destruction and accumulation of debris will make it more difficult to breathe. If the infection also reaches the blood vessels, this debris can hinder circulation and trigger formation of clots (thromboses). The intensity of these reactions will vary depending on individual genetics or health, but also on the extent of the initial infection.  

There is a delicate balance among all the molecules involved in the immune defence. “Hyperinflammation” or a “cytokine storm” occurs when the body reacts disproportionately. That’s what caused most of the deaths related to the Spanish influenza a century ago. It also explains the vast majority of the respiratory distress cases that occurred with SARS in 2003, and with COVID-19 now.  

Hyperinflammation can spread throughout the body and trigger a generalized infection. Patients then can die from kidney failure, liver disorders or too great a drop in blood pressure.  



The third line of defence: adaptive immunity  

This leads us to the third phase of the immune defence, which takes two forms. An army of cells is raised, equipped to destroy the invader more specifically (cell response). At the same time, antibodies are mass produced, capable of paralyzing the same invader quickly (humoral immune response). Because this double immune response is more specific, it will take a few days to deploy.  

However, once they are in production, this second wave of cells and these antibodies remain present in the body.  They are abundant in the weeks or months after an infection, and then remain latent for months or years, or even for a lifetime. They immunize a person who has already suffered from a disease.  

This is the basis of vaccination. It immunizes people in advance by exposing them to fragments of the virus (fragments of RNA or viral proteins, for example). This gives them time to manufacture antibodies before they are infected.  

Several drugs tested against COVID-19 were antivirals (Remdesivir, for example), but some known anti-inflammatories were also tested.  

This was the case for hydroxychloroquine, an antimalarial that showed some antiviral efficacy in vitro. But it is mainly known for its anti-inflammatory effects in the treatment of autoimmune diseases, such as lupus. Research has not yet confirmed this drug’s efficacy COVID-19. However, in June, British researchers announced that dexamethasone, a well-known anti-inflammatory corticosteroid, reduced mortality by one third in patients who were intubated or supplied with oxygen.  

But beware: there has not been any peer-reviewed publication of the results of this research. The researchers responsible for the study also mentioned that the drug had no significant effect on patients whose condition was less critical.  

This isn’t surprising. The immune response is an essential factor in the immune defence. If a drug that could inhibit this response is used too soon, it could do more harm than good. That explains why the medical authorities still strongly recommend against using these drugs to treat COVID patients. Except in the emergency room, in the critical phase.  

This is another illustration of the complexity of the immune system, and the difficulty of finding a universal drug! 

Cet article a initialement été publié sur le site de l’Agence Science-Presse.


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