How Covid-19 kills and why it matters.
The human body is attacked by viruses every second of every day. There are over 380 trillion viruses in the human body and we inhale over 100 million every day. So how do any of us stay alive? It is a bit complicated.
Viruses themselves are not technically alive. In fact, outside of an infected cell, a virus is technically known as a virion and does nothing, but virus will do for this discussion. The virus is a collection of nucleic acids (RNA or DNA), surrounded by a protein coat, waiting to enter a host cell. Once inside the cell the virus becomes “alive” and those nucleic acids act a new set of instructions, directing the cell to make more viruses. When enough viruses are produced, the host cell ruptures, releasing the viruses to spread to next cell.
How do viruses enter the cell and how do they know which cell to enter? The virus really doesn’t know anything. The protein shell contains the nucleic acids, but also acts as a “key”, allowing entry to some cells, but not others. Sometimes this occurs through the fusion of the viral protein coat with the cell membrane, but more often viruses enter through cell membrane receptors. Receptors are doorways through the cell membrane, allowing signals to be received by the cell and desired substances to move in and out.
In Covid-19 disease, the SARS-CoV-2 virus enters epithelial cells of the lungs through the ACE-2 membrane receptor. Once inside, viral replication occurs, creating many more viruses and killing the epithelial cell. Left unchecked the virus kills millions of epithelial cells, damaging the lungs and causing shortness of breath.
However, the body does not take this attack lying down. The innate immune system (the immediate, non-specific immune system) has a number of infection fighting components that respond to an infection, even if the infecting virus has never been seen before. Damage-associated pattern recognition receptors recognize patterns associated with damage to infected cells and pathogen associated molecular pattern receptors recognize viruses (looks like a duck, quacks like a duck = some new kind of duck). Both receptors induce inflammatory cytokine release, activating an immune response.
In response, non-specific immune cells move to areas of cellular damage and inflammation. Natural killer cells destroy infected cells, slowing viral reproduction. Macrophages ingest and destroy viruses. Importantly, the macrophages present antigens, portions of the virus with a recognizable pattern, to T and B-lymphocytes. These lymphocytes learn to recognize the virus and are key components of the adaptive immune system. They antigen specific cells are the basis of targeted the acquired immune system (is supposed) to take over the immune response after the first 3-4 days of infection.
T lymphocytes recognize and bind to the virally infected cells. This is more specific than natural killer cells and continues after natural killer cells are exhausted. B-lymphocytes learn to recognize the virus and then replicate, with their offspring becoming plasma cells, which produce antibodies to the virus. The antibody binds to virus and marks it for destruction by a chemical cascade or ingestion by macrophages.
Vaccines target these same T and B-lymphocytes, “priming” the adaptive immune system by presenting antigens so that a vigorous, pathogen specific response is ready when exposure occurs.
So how does this process fail and why does it matter?
SARS-CoV-2 appears able to evade the innate immune system, delaying an immune response. Preventing the immune system from sounding the alarm has devastating consequences. The innate immune system, when finally activated, over responds. The activation of the more targeted adaptive immune system is delayed. The virus is allowed to reproduce nearly unchecked. Once the innate immune system “catches up”, the response is overwhelming, disproportionate and ultimately damaging to the patient.
In many or most infected patients, the immune system responds sufficiently quickly and effectively, so that patients are minimally or even asymptomatic. When the immune system does not respond appropriately, we see classic symptoms of severe Covid-19.
Late and overwhelming innate immune response induces the “cytokine storm”. So what is it and why does it matter? When the cytokine storm occurs, all manner of bad things happen. This is why so many Covid-19 patients present will bizarre and often unexpected symptoms.
The human body operates in is kept alive in a narrow range of conditions. Temperature 95-100. Too cold, the patient becomes confused, bleeds spontaneously, suffers cardiac arrhythmias and dies. Too hot and proteins denature, the brain cooks, the patient dies. The same limits exist for pH, oxygen level, fluid balance, electrolyte levels and so forth.
The same is true of the immune system. Too little activity, viruses, bacteria and fungi kill. Too much immune activity and the body attacks itself (lupus, rheumatoid arthritis, Sjogren’s and presumably Parkinson’s, Alzheimer’s, etc). A malfunctioning immune system affects other systems, most importantly the blood clotting system.
The principal symptoms of severe Covid-19 disease are due to dysregulation of the innate immune system and a malfunctioning clotting system.
The excess immune activation and cell trafficking fills the lungs a cesspool of excess immune cells and dying epithelial cells. Not good for pulmonary function.
The clotting system is delicate balance of pro-clotting and anti-clotting mechanisms. Too much clotting, we have strokes, heart attacks, pulmonary embolisms and we die. Too little clotting, we bleed precipitously and we die. The inflammation of the cytokine storm in Covid-19 impairs production of anticoagulant factors that keep the clotting system in balance, leading to “sticky” blood and microthrombosis (multiple diffuse blood clots).
So we have blood clots in bad places, an immune system off the rails. and junk in the lungs. This is obviously not good. However, given the opportunity, the body has mechanisms to fix most of what has gone wrong. Autopsies of Covid-19 patients in New York demonstrated wide spread clots in the lungs, but also extensive angiogenesis, the formation of new blood vessels to replace damaged vessels.
What needs to be done?
Stop the cytokine storm, restore the immune system and allow the body to heal itself.
How is that achieved?
Leronlimab
Leronlimab is a monoclonal antibody that binds to and occupies the CCR5 receptor, stopping the response of immune cells to an important cytokine, the chemotaxic cytokine (chemokine) CCL5/RANTES.
As has been discussed widely, blocking RANTES:
Stops the cytokine storm. Macrophages, natural killer and other immune cells stop trafficking to areas of infection, removing additional fuel from the fire and stopping the vicious circle of inflammation.
Macrophages repolarize from a pro-inflammatory state to normal state, so that they ingest and destroy viruses, as well as continuing to teach B and T how to recognize SARS-CoV-2.
Reverse immune exhaustion in existing T lymphocytes so that resume targeting and destroying virally infected cells.
Reverses cytokine-driven hypercoagulation and reduces the risk of new clot formation.
There are many therapeutics under development for Covid-19. Only one, Leronlimab stops the cytokine storm. Not just one cytokine, not just one symptom, the whole inflammatory pathway and resultant syndrome.
The more quickly the medical and regulatory communities recognize this, the sooner we will stop the unnecessary deaths and disruption of lives and livelihoods worldwide. Let’s get on it.
The human body is attacked by viruses every second of every day. There are over 380 trillion viruses in the human body and we inhale over 100 million every day. So how do any of us stay alive? It is a bit complicated.
Viruses themselves are not technically alive. In fact, outside of an infected cell, a virus is technically known as a virion and does nothing, but virus will do for this discussion. The virus is a collection of nucleic acids (RNA or DNA), surrounded by a protein coat, waiting to enter a host cell. Once inside the cell the virus becomes “alive” and those nucleic acids act a new set of instructions, directing the cell to make more viruses. When enough viruses are produced, the host cell ruptures, releasing the viruses to spread to next cell.
How do viruses enter the cell and how do they know which cell to enter? The virus really doesn’t know anything. The protein shell contains the nucleic acids, but also acts as a “key”, allowing entry to some cells, but not others. Sometimes this occurs through the fusion of the viral protein coat with the cell membrane, but more often viruses enter through cell membrane receptors. Receptors are doorways through the cell membrane, allowing signals to be received by the cell and desired substances to move in and out.
In Covid-19 disease, the SARS-CoV-2 virus enters epithelial cells of the lungs through the ACE-2 membrane receptor. Once inside, viral replication occurs, creating many more viruses and killing the epithelial cell. Left unchecked the virus kills millions of epithelial cells, damaging the lungs and causing shortness of breath.
However, the body does not take this attack lying down. The innate immune system (the immediate, non-specific immune system) has a number of infection fighting components that respond to an infection, even if the infecting virus has never been seen before. Damage-associated pattern recognition receptors recognize patterns associated with damage to infected cells and pathogen associated molecular pattern receptors recognize viruses (looks like a duck, quacks like a duck = some new kind of duck). Both receptors induce inflammatory cytokine release, activating an immune response.
In response, non-specific immune cells move to areas of cellular damage and inflammation. Natural killer cells destroy infected cells, slowing viral reproduction. Macrophages ingest and destroy viruses. Importantly, the macrophages present antigens, portions of the virus with a recognizable pattern, to T and B-lymphocytes. These lymphocytes learn to recognize the virus and are key components of the adaptive immune system. They antigen specific cells are the basis of targeted the acquired immune system (is supposed) to take over the immune response after the first 3-4 days of infection.
T lymphocytes recognize and bind to the virally infected cells. This is more specific than natural killer cells and continues after natural killer cells are exhausted. B-lymphocytes learn to recognize the virus and then replicate, with their offspring becoming plasma cells, which produce antibodies to the virus. The antibody binds to virus and marks it for destruction by a chemical cascade or ingestion by macrophages.
Vaccines target these same T and B-lymphocytes, “priming” the adaptive immune system by presenting antigens so that a vigorous, pathogen specific response is ready when exposure occurs.
So how does this process fail and why does it matter?
SARS-CoV-2 appears able to evade the innate immune system, delaying an immune response. Preventing the immune system from sounding the alarm has devastating consequences. The innate immune system, when finally activated, over responds. The activation of the more targeted adaptive immune system is delayed. The virus is allowed to reproduce nearly unchecked. Once the innate immune system “catches up”, the response is overwhelming, disproportionate and ultimately damaging to the patient.
In many or most infected patients, the immune system responds sufficiently quickly and effectively, so that patients are minimally or even asymptomatic. When the immune system does not respond appropriately, we see classic symptoms of severe Covid-19.
Late and overwhelming innate immune response induces the “cytokine storm”. So what is it and why does it matter? When the cytokine storm occurs, all manner of bad things happen. This is why so many Covid-19 patients present will bizarre and often unexpected symptoms.
The human body operates in is kept alive in a narrow range of conditions. Temperature 95-100. Too cold, the patient becomes confused, bleeds spontaneously, suffers cardiac arrhythmias and dies. Too hot and proteins denature, the brain cooks, the patient dies. The same limits exist for pH, oxygen level, fluid balance, electrolyte levels and so forth.
The same is true of the immune system. Too little activity, viruses, bacteria and fungi kill. Too much immune activity and the body attacks itself (lupus, rheumatoid arthritis, Sjogren’s and presumably Parkinson’s, Alzheimer’s, etc). A malfunctioning immune system affects other systems, most importantly the blood clotting system.
The principal symptoms of severe Covid-19 disease are due to dysregulation of the innate immune system and a malfunctioning clotting system.
The excess immune activation and cell trafficking fills the lungs a cesspool of excess immune cells and dying epithelial cells. Not good for pulmonary function.
The clotting system is delicate balance of pro-clotting and anti-clotting mechanisms. Too much clotting, we have strokes, heart attacks, pulmonary embolisms and we die. Too little clotting, we bleed precipitously and we die. The inflammation of the cytokine storm in Covid-19 impairs production of anticoagulant factors that keep the clotting system in balance, leading to “sticky” blood and microthrombosis (multiple diffuse blood clots).
So we have blood clots in bad places, an immune system off the rails. and junk in the lungs. This is obviously not good. However, given the opportunity, the body has mechanisms to fix most of what has gone wrong. Autopsies of Covid-19 patients in New York demonstrated wide spread clots in the lungs, but also extensive angiogenesis, the formation of new blood vessels to replace damaged vessels.
What needs to be done?
Stop the cytokine storm, restore the immune system and allow the body to heal itself.
How is that achieved?
Leronlimab
Leronlimab is a monoclonal antibody that binds to and occupies the CCR5 receptor, stopping the response of immune cells to an important cytokine, the chemotaxic cytokine (chemokine) CCL5/RANTES.
As has been discussed widely, blocking RANTES:
Stops the cytokine storm. Macrophages, natural killer and other immune cells stop trafficking to areas of infection, removing additional fuel from the fire and stopping the vicious circle of inflammation.
Macrophages repolarize from a pro-inflammatory state to normal state, so that they ingest and destroy viruses, as well as continuing to teach B and T how to recognize SARS-CoV-2.
Reverse immune exhaustion in existing T lymphocytes so that resume targeting and destroying virally infected cells.
Reverses cytokine-driven hypercoagulation and reduces the risk of new clot formation.
There are many therapeutics under development for Covid-19. Only one, Leronlimab stops the cytokine storm. Not just one cytokine, not just one symptom, the whole inflammatory pathway and resultant syndrome.
The more quickly the medical and regulatory communities recognize this, the sooner we will stop the unnecessary deaths and disruption of lives and livelihoods worldwide. Let’s get on it.
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