Stress Theory, Critical Illness — and COVID-19

Normally the stress mechanism works quietly and unobtrusively to repair tissues and regulate organs, but when it becomes hyperactive it harmfully depletes its substrates, disrupts organ function, and damages tissues. These harmful effects manifest as disease.

Seemingly unrelated stresses activate the stress mechanism via combinations of tissue disruption and nervous activity, including emotional activity. Furthermore, vertebrate organs and tissues are highly specialized, and react to stresses in various ways. For example, tissues that are heavily innervated and/or rich in tissue factor (a specialized protein) react more readily to stresses. Because of these and other variables, the stress mechanism generates a bewildering blizzard of what appears to be distinctly different diseases and syndromes, but in fact all forms of disease are closely related because they all result from stress mechanism hyperactivity. This explains why seemingly unrelated diseases share symptoms and relationships that cannot be explained by conventional medical theory. For example, most diseases cause inflammation, increased immune activity, and fever. Diabetes, hypertension, obesity, cancer, and heart disease are closely-related. The stress mechanism explains these observations.

The lung is the primary “target organ” for all forms of stress because:

1. It is rich in tissue factor, which activates blood enzyme factor VII.
2. It is densely innervated by the autonomic nervous system, which activates blood enzyme factor VIII.
3. Its delicate, highly specialized tissues are easily attacked by inhaled pathogens and toxic substances.

Coronaviruses attack the delicate vascular endothelium in lung tissue. Lung tissues are highly specialized to optimize gas exchange. This disruption incites an inflammatory reaction, which floods the lung with exudates (mucus) that impede gas exchange and cause a fearsome sense of suffocation.

The inflammation releases tissue factor from lung tissues into flowing blood and activates nervous receptors that also release von Willebrand Factor into flowing blood. The fearsome sense of suffocation produced by the mucus exaggerates the nervous activity and releases additional VWF into blood. Tissue factor activates blood enzyme factor VII, and VWF activates blood enzyme factor VIII. The combined elevations of factors VII and VIII enzymatically interact with factors IX and X to generate thrombin, soluble fibrin, and insoluble fibrin in flowing blood, which causes systemic inflammation and increases blood viscosity, blood coagulability, and immune activity.

All these effects undermine tissue perfusion, tissue oxygenation, and organ function, and they exhibit “positive feedback” so that they grow worse with time. Often the first clinical sign of this systemic inflammation is fever and tissue edema. As the systemic inflammation worsens, it progressively disrupts organ function. The brain, like the lung, is rich in tissue factor and autonomic innervation, so that it is quick to manifest delirium and dementia. The afflicted kidneys cease to produce urine. The afflicted bowel ceases digestion and peristalsis. These distant and seemingly unrelated organ disruptions are called “multi-organ failure syndrome” (MOFS). The term “syndrome” reflects the inability of conventional medical theory to explain these observations or provide a means to treat them.

It has been widely noted that elderly patients with pre-existing chronic illnesses and obesity suffer increased risk from COVID. That is because chronic illnesses are caused by subclinical stress mechanism hyperactivity that inexorably damages tissues and exaggerates the harmful effects of COVID. Treatments with corticosteroids and NSAIDs help somewhat to inhibit inflammation, and sedatives inhibit fear and mitigate the release of VWF, but these measures have limited therapeutic value.

From the perspective of stress theory, COVID is a critical illness that is essentially the same as other life-threatening forms of critical illness, including eclampsia, ARDS (adult respiratory distress syndrome), SIRS (systemic inflammatory response syndrome), SARS (severe acute respiratory syndrome), MERS (middle-eastern respiratory syndrome), MOFS (multi-organ failure syndrome), pneumonia, gas gangrene, sepsis, asthma, severe burns, major trauma, and the surgical stress syndrome, all of which are caused by the excessive release of tissue factor into systemic circulation plus harmful nervous activity that induces excessive thrombin generation. Note that the term “syndrome” means “we don’t know” (i.e., conventional medical theory cannot explain these phenomena).

The lung also reacts to systemic stress induced elsewhere in the body, even though lung tissue isn’t directly affected. For example, severe burns, inadequately controlled surgical stress, major trauma, and bacterial infections, all of which induce systemic stress mechanism hyperactivity, can cause pulmonary inflammation that manifests as ARDS (adult respiratory distress syndrome) even though the lung tissue is not directly attacked. This is because the rich concentration of tissue factor and the intense autonomic innervation of the lung make it a “target organ.”

Treatment

Since conventional theory cannot explain critical illness, it cannot offer an effective treatment strategy. Stress theory indicates that the following combination of treatments should inhibit stress mechanism hyperactivity that facilitates the viral attack, restore tissue perfusion, tissue oxygenation, and organ function, and thereby optimize outcome in COVID and other forms of critical illness:

1. Elective endotracheal intubation to isolate the COVID contagion from health care workers and provide respiratory support as needed.
2. “Permissive” hypercarbia by maintaining exhaled CO₂ concentrations in the range of 50-100 torr. Patients should NEVER be hyperventilated for any reason. Hyperventilation harmfully depletes CO₂ tissue reserves that are essential for life. Mild hypercarbia optimizes tissue perfusion, tissue oxygenation, antibiotic penetration, and organ function.
3. Generous narcotic treatment to control subconscious nociception that releases VWF into blood.
4. ½ MAC general anesthesia to inhibit consciousness and control fear and anxiety that harmfully releases VWF into blood.
5. Magnesium sulphate treatment to control thrombin activity.
6. Antibiotic therapy as needed to control any bacterial infestation.

These synergistic treatments should safely enable afflicted COVID patients to rid themselves of the offending infestation. They could be used to control stress in all forms of critical illness. They should be equally effective for treatment of Lyme disease, MRSA (methicillin-resistant staphylococcus aureus) and other stubborn infections caused by “facultative anaerobes.”

At present there is no direct antidote for tissue factor released into blood, but it should be possible for pharmaceutical development to produce such a product, and it should theoretically be safer and more effective than magnesium sulphate.

Unfortunately, these treatments are not likely be readily accepted, regardless of their sound scientific foundation. Stress theory is complex, confusing, counterintuitive and at odds with entrenched dogma, and most physicians are loathe to consider anything other than orthodoxy for fear of collegial criticism. One can only hope that this will change with time.