COVID-19 vs the human immune system

Scientists are trying to identify the best strategies to win the war against COVID-19

COVID-19 vs the human immune system, a microscopic war with major health consequences
A medical worker looks at CT scans at the Huoshenshan field hospital in Wuhan – Photo: Wang Yuguo/Xinhua via AP
English 13/06/2020 14:29 Berenice González Durand Mexico City Actualizada 15:11
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The attack begins once the intruder is detected. When the immune system recognizes a strange molecule, it begins preparing the body to defend itself in a natural response that has accompanied humans through their evolution. With over 7 million COVID-19 cases in the world, research on the virus inside the human body has become fundamental to try to understand why some people can recover with just a bit of oxygen while other succumb to the virus once it reaches their lungs, heart, kidneys, intestine, and brain.

Scientists around the world, such as doctor Irani Theraian, an expert on infectious diseases of the Victorian Service of Infectious Diseases in Melbourne, Australia and an Honorary Member of the Nossal Institute for Global Health, confirms that 80% of COVID-19 cases are still mild, but understanding the immune response in all cases (both mild and serious) is highly important for it not only allows a better understanding of the way in which the virus attacks the body but also of the effectiveness of dozens of treatments that are being currently tested and, of course, it adds to the development of the vaccine.

Battlefront
Once the pathogen attacks, the immune system responds in two ways: the innate response and the adaptative response. The first one does not have memory and is in charge of increasing blood flow to the infected areas. Cells and certain substances, like proteins and cytokines, try to stop the infection. The cells involved in the innate response are macrophages, neutrophils, dendritic cells, mast cells, eosinophils, basophils, and NK cells, a powerful battalion that launches a war against the pathogen. The frontline is comprised of macrophages, cells that devour the waste present at almost all body tissues. When the infection is mild, this first squadron will be enough to defeat the enemy.

On the other hand, the adaptative response is in charge of producing antibodies to destruct the pathogen. The cells that partake in this process are a special kind of leucocytes called lymphocytes. B and T cells are their main kinds. It must be stressed that in this kind of response, the body is able to remember the pathogens it has already met and that is why it knows how to fight them in the future, but immune memory is still unknown in the case of this virus.

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That shows the immune system tries to neutralize the pathogen to prevent it from penetrating cells at all costs, however, it is not a simple fight. The battle, literally, leaves the body breathless, for as the immune system combats, the transfer of oxygen to the body is interrupted. White cells release inflammatory molecules that call more cells to attack and kill the cells infected by the virus. The lungs become a battlefront full of dead cells and liquid, an underlying pathology of pneumonia, with its corresponding symptoms.

The virus can win the battle in other ways. SARS-CoV-2 seems to evade the immune system by inhibiting the production of interferon macromolecules produce and that is secreted by host cells as a response to the presence of the pathogen to prevent the virus from entering into them. On the other hand, some immune systems generate the so-called cytokine storms. The immune system is overstimulated and attracts more aggressive cells to fight the virus until its loses controls and causes a rampant inflammation that kills the body since cytokines are proteins that do not only generate local inflammation but that cause it in several organs, such as the brain, the liver, and the bone marrow since molecules travel through the blood and arrive at those organs. It must be said that this does not only happes in the fight against the new coronavirus, according to information from the University of Alabama, but this organic lack of control also happens to at least 15% of those who fight any serious infection.

Experts seem to disagree on the impact of these storms. While to some people these hyperinflammatory conditions provide the opportunity to create clinical trials for drugs directed to specific cytokines in patients infected with COVID-19, to others, convincing data is still missing and there is the risk of these drugs suppressing the immune response required by the body to fight the virus.

The immune system is less effective as time goes by, hence elderly people have a higher risk. The same happens with people with diseases like diabetes, hypertension, or obesity, but researchers are also trying to understand why the virus can seriously damage other younger bodies without health issues. The answer is multifactorial, but the influence of the genetic factors has not been left aside, for even the cytokine storms could be benefited by a kind of mutations, as has been observed in other coronaviruses, such as H1N1.

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Furthermore, experts in respiratory diseases and genetics of the University of Oxford are studying the gene that codes the ACE2, the enzyme linked to the external surface of cells in lungs, vessels, heart, kidney, and intestines, and that has a fundamental role in the access to the pathogen. It is possible that ist genetic variants could make some individuals more susceptible to the virus penetrating their cells.

One of the most ambitious projects to study the relationships between genetics and the new virus is carried out by the head of Molecular Medicine at the University of Helsinki. Bioestadist Andrea Ganna has launched the COVID-19 Host Genetics Initiative with over a hundred studies and an agreement with biobanks all over the world to share DNA information that has been gathered before the pandemic to be able to identify the genetic variants associated to COVID-19.

The heart’s secrets
In the article "How does coronavirus kill?" (Meredith Wadman et al), recently published by Science, the journey of the virus inside the body is tracked. The infection begins when an infected person expels drops with the virus and another person inhales them. SARS-CoV-2 finds a warm reception at the lining of the nose. Scientists from the Wellcome Sanger Institute have found that cells in this part of the body are quite rich in ACE2. The intruder is inside and “kidnaps” the machinery of the cells, making innumerable copies of itself and invading new cells. If the immune system does not counterattack SARS-CoV-2 on its initial phase, the virus goes down the throat to attack the lungs, where, as has been explained, it can become mortal, but that is not the end of it. It is believed that a fraction of the virus exerts a direct attack on other organs, such as the kidneys.

Experts have also found that on its way in the human body, the coronavirus is able to damage blood vessels and the heart, which are highly involved in the fatal end of the disease. Several investigations at Intensive Care Units throughout the world have noticed that around 30% of patients have abnormal coagulation, which could accelerate the mortality of the disease.

Scientists are fighting to understand exactly what causes cardiovascular damage. A hypothesis is that the virus directly attacks the heart’s lining and blood vessels which, as in the nose and lungs, are rich in ACE2 receptors. Anot; however, the cytokine storms could devastate the heart as it does with other organs.

The battle inside and outside the body is still too long to know exactly which are the pieces of the puzzle that will call a truce on the pandemic, but everyday clues cannot be dismissed.

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