Tackling Long Covid

Long-COVID-19 (LC) is a complex and often debilitating condition that affects millions of people worldwide. With over 200 different symptoms impacting multiple organ systems, Long-COVID-19 presents a significant challenge to patients and health practitioners alike.

Recent estimates suggest that approximately 10% of all COVID cases transition to Long-COVID-19, equating to over 65 million people globally, with an estimated 260,000 cases in New Zealand and 1.2 million in Australia. The impact on sufferers’ lives can be profound, with 3–18% of people with Long-COVID-19 reporting an inability to return to work at 12-month follow-up, leading to a substantial burden on families, healthcare systems and the workforce. In terms of numbers in New Zealand, this may be as low as 7,800 people, and as high as 46,800 being unable to return to work.

In the quest to understand Long-COVID-19, the focus has shifted from angiotensin-converting enzyme 2 (ACE2) inhibitors to a more comprehensive approach targeting core pathologies. One key aspect of monitoring Long-COVID-19 is the D-dimer test, which measures protein fragments released when blood clots dissolve. This test was historically used to monitor specific blood clotting conditions and is undetectable, or at extremely low levels, when in normal range. Long-COVID-19 symptom resolution can occur when the creating and breaking down of clots happen at an equal rate, but clot formation may still be far above normal blood clotting rates.

Beyond just resolving symptoms, monitoring D-dimer levels offers us insight into excess clot formation. Similar to how high blood sugars in diabetes may not manifest symptoms but are crucial to address and monitor through blood tests, the absence of symptoms in Long-COVID-19 does not diminish the importance of treating excessive clotting and potential endothelial damage until D-dimer levels normalise in blood tests.

Recent research has led to the selection of specific supplements for managing Long-COVID-19.

These five areas of focus are:

  1. Enzymes for protein debris and folded and misfolded proteins/amyloids
  2. Antioxidants, offsetting the specific and excess reactive oxygen species (ROS) produced with the inflammatory reactions
  3. Supporting inflammatory pathways through down regulation
  4. Addressing nutritional deficiencies both pre-Long-COVID-19 and those induced by Long-COVID-19
  5. Supporting the innate immune system to minimise re-occurrence


Enzymes

Enzyme support is a promising starting point, as endothelial damage from acute COVID can be sufficient to create many of the Long-COVID-19 symptoms. If Long-COVID-19 persists beyond 3 months, the pathology may be due to the generation of damaged-cell debris and folded or misfolded proteins, similar to the pathology seen in cognitive and blood dyscrasia conditions like Alzheimer’s, dementia, Parkinson’s and concussion syndrome.

Proteolytic enzymes such as Nattokinase, Serrapeptidase and Lumbrokinase (Boluoke) have shown promise in reducing folded proteins and inflammatory debris. Lumbrokinase in particular has been found to be the most active proteolytic enzyme, functioning at 10+ times (an order of magnitude) the enzymatic power of Nattokinase and Serrapeptidase. As each of these enzymes acts on a variation of proteins, and with the folded protein and debris field presenting as diverse and extensive, a blend of multiple enzymes appears to be the most likely approach, at least until we know more.

Antioxidants

Again, a mix of antioxidants, just like a broad approach for enzymes, appears to produce the greatest support. A few key antioxidants stand out as particularly targeted for the oxidative stress generated with Long-COVID-19. Liposomal glutathione has been shown to be particularly beneficial for supporting many Long-COVID-19 symptoms. Its ability to cross the blood-brain barrier supports neural inflammation (seen corresponding with the brain fog and cognitive impact of Long-COVID-19) but also inflammation seen along the enteric nerve tissue and debris-caused capillary inflammation. Glutathione has a very strong sulphur taste, which many finde very unpleasant. An alternative is to take N-Acetyl Cysteine (NAC), a precusrsor to Glutathione instead; this avoids the tatse. Lutein, another key antioxidant, has an affinity for retinal, optic nerve, cardiometabolic and central nerve tissue support. The combination of these two antioxidants, along with a blend of other antioxidants, appears to offer the strongest support for downgrading ROS and overall oxidative stress seen in Long-COVID-19. Nrf-2 is also a potent antioxidant, supporting the glutathione detoxification pathways.

Anti-inflammatories

Addressing inflammation and cytokine storms is another key aspect of Long-COVID-19 management. Broad-spectrum approaches found in fish oils (EPA/DHA/SPMs) and liposomal vitamin C are trending as the most utilised options. Curcumin, especially Nano-Curcumin, Boswellia and PEA have replaced NSAIDS and show promise in supporting the modulation of chronic inflammation associated with Long-COVID-19.

Nutritional deficiencies

Whether pre-existing or depleted from managing Long-COVID-19’s ongoing inflammatory response, nutritional deficiencies are common and may increase the risk of developing the condition or even prevent resolution. B vitamins (particularly B6 and B12), molybdenum, protein, selenium, vitamin D, and zinc are among the most common deficiencies observed. Addressing these deficiencies through targeted supplementation and/or dietary changes may support the body’s healing processes and improve patient outcomes.

Innate immune system

Finally, it is important to address the patient’s innate immune response strength. COVID infections are in part a race to adaptive acquired immune response. The first line of defence is the innate immune response, but COVID inhibits macrophages, among other mechanisms, to protect itself from the immune system. If COVID exceeds the innate system before the acquired system kicks in, then illness and cellular damage occur. It is a large component of the risk factors observed: nutritional deficiencies, diabetes, hypertension and advanced age are all areas where we commonly see reductions in innate immunity. Supporting patients with known nutritional deficiencies, as well as lifestyle interventions that support healthy stress management, good sleep and optimal gut health may bolster the innate immune response.