Cytokine Storm - Acute Respiratory Distress Syndrome (ARDS):

The biggest fear surrounding the COVID-19 pandemic is developing pneumonia and what is sometimes called severe acute respiratory syndrome (SARS) or acute respiratory distress syndrome (ARDS). It is not the coronavirus which is actually killing people, it is the acute respiratory syndrome resulting from a cytokine storm, leading to sepsis, hypoxia, the inability to breathe and organ failure that can follow it. Most people that get coronavirus will have a mild case; some will have the virus and not have any symptoms at all and for many others it will feel like the flu. We don't have an accurate figure of how many people are infected because so many have mild or no symptoms and are not getting tested. The people most at risk of developing ARDS and dying tend to be the elderly and those that are immune-compromised.

Deepak Chopra does the best job I’ve found outlining the disease process and what makes COVID-19 so debilitating. A link to his webpage is here. He says that it is not just the virus that harms the infected, but their own immune systems.

• “The pneumonia which accompanies COVID-19 is not directly caused by the virus but rather through fibrosis caused by runaway cytokine storms within the respiratory system. The virus sabotages the infected person’s normal immune response with a scorched earth strategy, destroying antibody cells while it is being destroyed itself. The resulting chaos elicits an ever-increasing intensity of inflammatory immune reactions, which eventually begin damaging the person in addition to the virus.
  
  
• The cyclical nature of the infection/inflammation feedback loop means that recovery from the virus can take many weeks until the immune system succeeds at clearing the viral load, and during that time the inflammatory response can spiral out of control at any time. Recovery from COVID-19 is not necessarily gradual progress, especially in the most severe cases. A cytokine storm resulting in respiratory damage can occur at the end of the infection as easily as the beginning.
  
  
• Acute respiratory distress syndrome (ARDS) and septic shock ensue. These potentially fatal conditions are not caused by the virus itself, but rather the immune system’s inflammatory response to the virus, with older groups possessing more chronic conditions that increase inflammatory load, thus more rapidly spiraling into complications that require hospitalization.
  
  
• Critical condition rates are also spread among demographic groups, with a significant increase in older groups and those with preexisting conditions. This is likely because higher rates of inflammation accelerate the progression to cytokine storms that damage the respiratory system and require critical care.
  
  
• Mortality rates are dramatically skewed toward the elderly and those with preexisting conditions, which is in keeping with the premise that a heightened inflammatory load is the deciding factor in whether the patient’s immune system is able to rebalance and clear the virus without fatally damaging the patient. Those with systemic inflammation are the most likely to die because their systems are already out of homeostasis.
  

It has been shown that lymphocytes dramatically decrease in advanced cases of infection. Natural killer (NK) cells and lymphocytes become exhausted and can’t keep up. We know that this is worse in the elderly and immunocompromised. One goal should be to increase NK cell function in the early stages of disease to help prevent this exhaustion from occurring. The key to induction of ARDS is something called NLRP3 inflammasomes. Once these are activated, they cause production of IL-1B, a very potent cytokine. This event initiates the cytokine storm and ensuing hypoxia – this signaling is what sets the dominoes falling.

Melatonin  has a protective effect and has been shown to prevent NLRP3 from being activated. Melatonin peaks in childhood and declines as we get older, especially over age 50. Children under age of 9 seldom exhibit severe symptoms. Young children have about 10 times the amount of peak melatonin then older individuals. NLRP3 is a direct target of melatonin. In animal models, melatonin reduces sepsis by decreasing pro-inflammatory cytokines, reduce reactive oxygen species (free radicals), and maintain mitochondrial homeostasis. Acute administration can short circuit the cytokine storm. None of the pregnant mothers in Wuhan China developed severe pneumonia or died. This is speculated to have been due to third semester of pregnancy, more than double the amount of melatonin is secretion than the first trimester. Melatonin had protective effect.

The spike protein on the Covid-19 virus can interact with the cell surface receptor ACE2, angiotensin I converting enzyme 2. The spike protein, which contains the receptor binding domain, makes contact with ACE2 which is facilitated by furin cleavage.

Recent studies have found that the Spike protein of SARS-CoV-2 is between 10 and 20 times more likely to bind to human ACE2 than the Spike protein of the early 2000s SARS-CoV strain and allows the virus to be activated anywhere in host tissues and organs, bind effectively to ACE2 recepters causing more damage and destruction in vital organs of the cardiovascular system and other pathways involving ACE2. This may be one important aspect in the progression to ARDS.

Research is looking into targeting ACE2 receptors, blocking the virus from attaching to these sites. Research is looking into the herbs  andrographis, urtica (stinging nettles), Sambucus (elderberry), Astragalus and butyric acid.
Vitamin C can also inhibit NLRP3 inflammasomes, explaining why IV vitamin C has been helpful in treating infections. IV vitamin C is being used in Chinese and New York Hospitals right now and all over the country. Vitamin C works on a number of levels. Supports production of Nitric oxide, reducing oxidative stress, regulating hypoxia signaling, helping mitochondrial membrane potential, altering furine expression and modulation of immune defenses to defend against progression of cytokine storm.