Example of Systemic Dysfunction

ME/CFS and Long COVID

THE CARCO STRESS MODEL: Carbon Monoxide Exposure → Peroxynitrite Formation in Capillaries → Fibrin Amyloid Formation → Microvascular Obstruction → Reduced Mitochondrial Oxygen Availability → Aerobic Energy Production Failure → Systemic Dysfunctions

ME/CFS and Long COVID share many of the same symptoms, including severe fatigue, post-exertional worsening, unrefreshing sleep, brain fog, pain and poor recovery.

Research has found fibrin amyloid microclots in both conditions.[1–3] These abnormal fibrin structures can resist normal breakdown and accumulate in the smallest blood vessels, restricting the passage of red blood cells and reducing oxygen delivery to tissues.

The Carco Stress Model connects this directly to the energy failure seen in ME/CFS and Long COVID:

Carbon monoxide exposure
→ fibrin amyloid formation
→ microvascular accumulation
→ reduced tissue oxygen delivery
→ impaired aerobic energy production and recovery
→ ME/CFS and Long COVID symptoms

Fibrin Amyloid Microclots Obstruct the Microcirculation

Fibrin amyloid microclots have been found in Long COVID and ME/CFS.[1–3] Unlike normal fibrin, these abnormal structures are resistant to normal breakdown and can remain in the circulation.

As they accumulate in the smallest blood vessels, they reduce the space available for red blood cells to pass. Increasing numbers of microvessels therefore become partially or completely unavailable for normal oxygen delivery.

Microvascular Obstruction Reduces Tissue Oxygen Delivery

Red blood cells carry oxygen to tissues through the smallest blood vessels. When fibrin amyloid microclots obstruct these vessels, oxygen-carrying red blood cells cannot reach all parts of the tissue normally.

Blood oxygen saturation can still appear normal because it measures the oxygen carried in the blood, not whether that blood can reach every tissue through the microcirculation.

Reduced oxygen extraction and vascular abnormalities have been found in both ME/CFS and Long COVID.[4–6]

Fibrin amyloid microclots → blocked microcirculation → reduced red-blood-cell passage → reduced tissue oxygen availability

Reduced Oxygen Causes Energy Production Failure

Cells require oxygen for normal aerobic energy production. When microvascular obstruction reduces oxygen delivery, mitochondrial ATP production cannot keep pace with cellular energy demand.

Research has found abnormalities in cellular energy metabolism in both ME/CFS and Long COVID.[7,8]

Ordinary activity therefore consumes available energy faster than it can be restored. Recovery becomes slower, repeated activity creates an accumulating energy deficit, and even small demands can eventually produce severe exhaustion and prolonged worsening.

Reduced oxygen delivery → impaired aerobic ATP production → incomplete energy recovery → accumulating energy deficit

Infection and Extensive Fibrin Amyloid Formation

THE CARCO STRESS MODEL: Carbon Monoxide Exposure → Infection →  Extensive Peroxynitrite Formation in Capillaries → Extensive Fibrin Amyloid Formation → Microvascular Obstruction → Reduced Mitochondrial Oxygen Availability → Aerobic Energy Production Failure → Rapid Systemic Dysfunctions

ME/CFS may develop gradually, but in many cases its onset is associated with an infection or another major physiological event. Long COVID, by definition, develops following SARS-CoV-2 infection.

The Impact of Increased Neutrophils

During period of Infection there occurs strongly increased platelet-neutrophil production. This massive cellular production occurs during severe infection, major injury, surgery, or tissue damage. Because severe physical stress creates a extensive supply of platelet-neutrophils, carbon monoxide exposure during this period greatly accelerates amyloid formation. This provides a mechanism by which a fibrin amyloid burden that might otherwise develop gradually could form much more rapidly.

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