CNCAV presents Romanians with a brief introduction to what pathogenesis means, the science that studies the mechanisms of illness, and this is because during the Coronavirus pandemic there was a lot of talk about the pathogenicity of the various viral variants that circulated, and are circulating throughout the world.
"IT'S READ! TIME OF PATHOGENESIS (BRIEFLY, ABOUT DISEASES)
Pathogenesis is the field of medical sciences that deals with the study of disease mechanisms. Understanding the pathogenesis means knowing exactly what is happening there and understanding where to intervene so that a disease, or its harmful effects, can be prevented/mitigated. Which means that, being a pathogenist, I have an applied knowledge of the entire universe of disease and all that it contains. And we know that each person is a universe in itself.
Why is it important not to ignore the pathogenesis of a disease? Because it allows us to see beyond some numbers and understand certain unexpected manifestations.
For example, in HIV infection, the essential question of pathogenesis has long been "why do we get AIDS?" As paradoxical as it may seem, the answer: "Because the virus destroys our CD4 cells" is not enough. The virus destroys CD4 cells in three weeks, and we progress to AIDS in 10 years.
How is it possible? The simplest answer to this question could be obtained if we ask ourselves a few correct questions: where are the CD4 cells? If you are quick to say: "in the blood", you are wrong. Only 2% of the body's CD4 cells are located in the blood. Where are the rest? Obviously, in the immune system. But the immune system is extremely diffuse. And the question "where is the immune system located in the body?" has some answers that might surprise and disappoint you in equal measure. The first: the secondary lymphoid organs, including the ganglia. The most handy answer. But in general, the cells in the lymph nodes are only destroyed relatively little and very, very late in HIV infection. Where then? At the level of the mucous membranes. Which? Well, what is the largest mucous membrane in the body? Digestive tract. The lamina propria contains the most immune cells in the entire body.
A second question follows: which CD4 T cells are depleted? Because, just like in Animal Farm, there are many CD4 cells, but some of them are more equal than others: naive CD4 cells are the ones just waiting to be trained. It is the central memory cells that begin to learn and prepare to respond to stimuli; memory transition cells are ready for action. Effector cells are those that directly interact with pathogens. All memory cells (central, transitional and effector) express the HIV coreceptor CCR5 and are direct targets of the virus.
Further. CD4 cells with different functions are located differently in the body. In immunology, the school is called "situs inducer". The service is referred to as the "effector site." Naïve cells stay at school in ganglia; Effector cells are at work at the interface with microbes, at the level of mucous membranes. There they are found by HIV and decimated (>90% of them) in 3 weeks. The most susceptible: precisely the cells that ensure the defense of the mucous membranes against microbes, called Th17 cells. Did I make your hair curly? We're just getting started.
But after learning all this, you're probably thinking "why does it take 10 years to get AIDS if the target cells are short-circuited?"
Because their simple elimination does not lead to AIDS. We experimentally eliminated CD4 cells from African green monkeys for a year and a half, and they did well and had a good time.
And then? Now an interesting and rather horrifying part begins: in the process of destroying CD4 cells, the human immunodeficiency virus induces a great firework in the digestive mucosa. From the inside (submucosa) to the surface. Destroyed cells release inflammatory markers. Other inflammatory cells also reach this level, being multiple cytokine products, and this whole process leads to the destruction of the epithelial cells of the digestive mucosa. From a continuous barrier, the mucosa is pierced more or less extensively.
Is it a problem? Sure.
Which? Because the intestine is full of bacteria involved in digestion. Normally, these bacteria are located in the lumen, where they find their way around. It constitutes the microbiome. Intestinal flora. Of better or worse quality, as we eat at fast food or at mom's, healthy, with plenty of fruits and vegetables. A flora maintained on a Western-type diet (ie, high in fat and sugar) is inflammatory per se. A Mediterranean diet (ie, high in fiber, vitamins, and minerals, associating consumption of fish rich in omega 3) can reverse this inflammation. Switching from a poor-quality diet to a healthy one high in cruciferous vegetables and lower in red meat can substantially alter the gut microbiome in just three weeks. But I digress.
Through the continuity solutions of the mucosa, the microbial flora leaves the lumen and first passes into the submucosa, from where it is taken into the portal circulation, reaches the liver and from there into the circulation. We are not talking about those large amounts that produce sepsis (bacteremia and septicemia), but small and very small amounts. Not only microbes, but fragments resulting from the destruction of microbes in the process. As effective in inducing inflammation as whole microbes. The process by which microbes move from the blood into the circulation is called microbial translocation. And it is the main cause of chronic inflammation in HIV infection. Chronic inflammation produces hypercoagulation and activation of T cells that accelerate the processes of division and aging, and are lost. Overall, markers of coagulation, inflammation, and translocation are the most important predictors of death in the HIV-infected patient. That is, HIV triggers a process by which we kill ourselves (well, it kills our microbes).
You will say: "very nice. Do you have proof?” Yes.
In African monkeys, in which infection with HIV-like viruses does not progress to AIDS, the digestive mucosa is preserved.
Blocking microbes in the gut with an LPS chelator improves the infection profile in pathogenic macaque infections.
Administration of a high-fat diet (hamburgers) produces progressive pathology, including in otherwise nonprogressive African monkeys.
You will say that none of this has anything to do with COVID. Really?
Just as HIV alters the intestinal mucosa from the inside, SARS-CoV-2 alters it from the outside. The highest abundance of ACE-2 and TMPRSS2 receptors is found on the surface of digestive mucosa. And the respiratory tract - and that's a mucosa, and there enter microbes from the air, which can translocate through the alveolar membrane. Once the digestive epithelium is destroyed, we end up in exactly the same pathogenetic scenario. If the body does not immediately eliminate the negative stimulus, the chronic inflammation induced by the translocation is responsible for all the side effects and long-term sequelae.
THAT IS WHY IT IS EXTREMELY DISTURBING TO SEE DOCTORS SAYING THAT THE WORLD HAS BEEN TURNED UPSIDE DUE TO A BASIC FLU. THIS IS NO ORDINARY FLU.
Massive and persistent mucosal damage has severe consequences. People don't realize that persistent poor quality inflammation (such as that induced by translocation) is the source of the conditions responsible for the death of three out of five people on this planet.
Chronic inflammation affects different organs and systems as follows:
- Heart and blood vessels: atherosclerosis and heart disease (the frequency of heart attacks is 5 times higher in HIV-infected patients who control the infection than in the general population);
- Digestive system: inflammatory disease, including Crohn's disease or ulcerative colitis;
- Joints: various forms of arthritis, including rheumatoid arthritis;
- Lungs: Allergies, asthma, COPD, lung cancer;
- Brain and spinal cord: paralysis, multiple sclerosis, etc.;
- Eyes: Macular degeneration, retinal degeneration, uveitis;
- Skin: acne, eczema, psoriatic reactions, etc.;
- Kidneys: chronic kidney disease, renal failure, nephritis;
- Pancreas: type 1 diabetes;
- Thyroid: thyroiditis;
- Liver: chronic hepatitis.
It's not a game. The basis of these chronic inflammatory conditions are exactly what I referred to above. In addition, a prolonged persistence of the virus can be recorded in certain sanctuaries, such as the kidney.
Add to all of this the persistent loss of smell and taste, and you have a pretty complete picture of an illness that is anything but the flu. And whoever says otherwise has no idea what they're talking about.
Not convinced? Read the article below. I am posting a single figure that clearly demonstrates that intestinal mucosal integrity markers are seriously altered by SARS-CoV-2 infection.
Text adapted from the post of Dr. Cristian Apetrei, Romanian professor in the Department of Microbiology and Molecular Genetics, member of the Center for Vaccine Research and the Postgraduate Program in Microbiology and Immunology (PMI) at the University of Pittsburgh, USA."
