Long COVID, Thromboinflammation and Immune Dysregulation

Functional Medicine Research with Dr. Nikolas Hedberg, DC

A new paper published in the journal Science entitled, “Persistent complement dysregulation with signs of thromboinflammation in active Long Covid” sheds light on the causes of Long COVID.

The authors begin by pointing out the current hypotheses about the causes of Long COVID, including persistent inflammation, autoimmunity, tissue damage, and viral reservoirs.

In this study, researchers followed 39 healthy individuals and 113 COVID-19 patients for up to a year to identify biomarkers associated with Long COVID. At the 6-month follow-up, 40 patients still experienced Long COVID symptoms. They collected blood samples and measured over 6500 proteins to identify potential biomarkers using computational tools and experimental evaluation.

In patients with Long COVID, there was an increased activation of the complement system, which is a part of the immune system that helps fight pathogens and damaged cells. This activation persists even after the acute phase of the disease. The complement system can cause damage to cell membranes, and in Long COVID patients, there is an imbalance in the formation of a complex called the terminal complement complex (TCC), also known as the membrane attack complex (MAC), which contributes to tissue damage.

Long COVID patients experienced increased markers of tissue injury in their blood, along with a thromboinflammatory signature. This means that there are signs of damage to tissues and an abnormal immune response involving the activation of endothelial cells and the breakdown of red blood cells. These findings suggest that Long COVID is associated with ongoing inflammation and potential blood clotting issues.

In patients with Long COVID, there are lower levels of antithrombin III, a protein that helps regulate blood clotting. This leads to increased cleavage by thrombin, which is a key factor in the formation of terminal complement complexes (TCCs).

Additionally, Long COVID patients show elevated markers of platelet activation and the presence of monocyte-platelet aggregates, particularly in cases where Long COVID symptoms persist for 12 months or more.

These patients also exhibit signs of antibody-mediated activation of the classical complement pathway, which is associated with increased levels of antibodies against cytomegalovirus (CMV) and Epstein-Barr virus (EBV).

In this study, the researchers also used a sensitive test to measure antinuclear antibodies (ANA) in patients with Long COVID. They found that patients with Long COVID had a higher prevalence of positive ANA results compared to those without Long COVID. Positive ANA tests can indicate autoimmunity.

Based on the data presented, it is suggested that Long COVID patients should undergo early cardiovascular assessment due to potential cardiovascular complications. Additionally, antiviral medications targeting SARS-CoV-2 or herpesviruses may help reduce inflammation and blood clotting in Long COVID patients. Therapies that target the terminal complement pathway could also be explored as potential treatment strategies for Long COVID and other post-infection syndromes.

Long COVID Clinical Applications

This paper confirms that inflammation of the blood vessels is common in Long COVID. Supporting microcirculation with herbs like ginkgo biloba, grape seed extract, and mango fruit powder can help reduce this inflammation and repair damaged blood vessels. These three herbs also are effective anti-viral agents against viruses like Epstein-Barr Virus (EBV) and Cytomegalovirus (CMV).

Ginkgo biloba has been shown to help improve the symptoms of Long COVID.

I use VascuSelect from Moss Nutrition which contains standardized forms of ginkgo biloba, grape seed extract, and mango fruit powder.

I also use palmitoylethanolamide (PEA) combined with luteolin to reduce inflammation and fight chronic viruses. Both of these are found in PEA Luteolin Select from Moss Nutrition. PEA and luteolin have been shown to work synergistically to help improve Long COVID symptoms.

Additional supportive compounds to reduce inflammation and balance the immune system in Long COVID patients include black cumin seed oil, curcumin, quercetin, resveratrol, fish oil, and vitamin D to name a few.

Hedberg Institute Members can download my latest Long COVID protocol by logging in.

Click here to learn more about the Hedberg Institute Membership.