Why Can COVID-19 Be Deadly? The 4 Keys That Explain It

COVID-19: In some people, the virus can bypass the immune system so that it reproduces freely, quickly enters and damages cells, causes an exaggerated inflammatory storm, and causes thrombosis.

These four reasons explain why COVID can be fatal. Why can some people experience Covid-19 with hardly any symptoms, and it can cause death in others?

The key is in the immune system. Instead, how SARS-CoV-2, the virus that causes Covid-19, manages to elude it, avoid it. And this not only happens in ancient people or with previous pathologies but also occurs in younger people.

Knowing in-depth how that happens, what mechanisms the virus uses to circumvent the immune system is key to curbing it. The more we know about it, the more tools we will have to prevent it from getting complicated.

Sant Pau researchers have taken a big step in this direction and have identified the “four horsemen of the viral apocalypse,” that is, the four mechanisms by which Covid-19 harms.

The work led by the coordinator of the HIV and AIDS Research Group and the COVID hospitalization of the Institut de Rercerca de Sant Pau-IIB Sant Pau and member of the Infectious Diseases Unit of the Hospital de la Santa Creu I Sant Pau has been published in EBioMedicine.

1. The Four Horsemen of the Viral Apocalypse

The study led by and entitled “The four horsemen of a viral Apocalypse: The pathogenesis of SARS-CoV2 infection (COVID-19)” identifies the four mechanisms by which the virus can end up causing severe acute respiratory syndrome ( SARS) due to coronavirus (CoV).

And the four horsemen of the apocalypse are as follows:

a. The Viral Circle

  • The virus manages to evade the innate response of the immune system.
  • This causes it to replicate in an uncontrolled way.
  • Faced with this situation, the immune system activates a hyperactive adaptive response, making the virus multiply without impediment, that is, to roam freely.

b. The Hyperinflammatory Circle

A disproportionate inflammatory response is generated that feeds back until it unleashes a veritable cytokine storm that affects various organs, especially the lung.

c. The Renin-angiotensin System Circle

The researchers call it “the circle of the non-canonical axis of the renin-angiotensin system.”
The renin-angiotensin axis is a hormonal system that mainly regulates blood pressure and which, among other things, also blocks the entry of the virus into cells.

But if this axis is reduced, and this is what happens in severe COVID, the lung is left without this defence mechanism, and the virus can easily invade its cells. This further favours the inflammatory damage caused by the disease.

d. The Circle of Coagulation

Inflammation and coagulation cause an infinite and very harmful circle in COVID.

The cytokine storm, that is, the surge of inflammatory substances, activates coagulation, generating a lot of thrombin, which triggers a thrombotic event (pulmonary thromboembolism).

This situation can lead to multi-organ failure that is associated with a very high mortality rate.

2. A Cocktail That Can Be Deadly

These four factors cause a state of hyper inflammation and hypercoagulability, and the consequences of this are foreseeable:

It can lead to severe lung injury, and the patient requires mechanical ventilation and intensive care. This situation can lead to the death of the patient.

3. Know the Virus to Defeat It

The Sant Pau study is one more step in the fight against Covid-19. “Knowing the pathophysiology is the first step to address the management of a disease adequately.”

“Knowing the mechanism that the virus uses to elude the host’s immune defence mechanisms or the mechanisms it uses to damage, will allow the design of adequate strategies to neutralize the dysfunctions or imbalances generated by the virus or by the consequences of the infection.”

The virus generates imbalances in different aspects that it is essential to know.

The study results show that the damage that occurs in organs by COVID-19, not only in the lung but also in many others, is generated through these immune mediation mechanisms, although logically, SARS-CoV-2 is the trigger.

It is logical to think that not all patients will evolve in the same way; therefore, knowing how to identify early those most likely to develop towards a life-threatening disease is very important.

For example, those at higher risk of thrombosis can be treated with anticoagulants and avoid thrombotic events.

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