Long Covid: Research updates & clinical Strategies

There are so many misconceptions about long COVID. The first is that it only happens to people who were sick before. The second is that you had to have a symptomatic infection to develop long COVID (post-acute COVID-19 syndrome or PACS). Approximately 20%. of PACS patients had asymptomatic COVID infections.

My predominant PACS cohort is made up of previously highly active and successful type-A mega achievers in their twenties and thirties. Many have experienced mental health concerns, severe stress, underlying immune challenges, silent autoimmune issues, poor blood sugar regulation, nutrient status or gut health. Some had previously lived in water-damaged buildings.

The most common persistent symptoms I am seeing in PACS patients suffering post-viral manifestations include fatigue, breathlessness, joint pain, chest pain, vision problems, shooting nerve pains, burning sensations, digestive issues, headaches, poor sleep, POTS, hair loss, hypoglycaemia, joint pain, anosmia & ageusia. Depression, brain fog and anxiety are extremely common. Most of these symptoms correlate with chronic fatigue, and chronic Lyme. Many of these patients experience a reactivation of Epstein-Barr virus, I see Lyme results coming back positive. Dysautonomia, mast cell activation and histamine-related symptoms and vagus nerve dysfunction are present in almost all patients but may express differently depending on the patient. Most of what I see in clinic correlates with all the studies which have been published in the last year. A pilot study that hasn’t even been released yet and is due to be presented at a conference later this year (ECCMID), suggests that most PACS symptoms are due to the virus’s action on the vagus nerve which drive POTS symptoms.

Another study published this year saw microbiome differences in PACS patients, with higher levels of Ruminococcus gnavus, Bacteroides vulgatus, and lower levels of Faecalibacterium prausnitzii,  the latter is associated with good gut diversity. Butyrate producers tend to be lower in PACS patients. Very low levels of butyrate producers and butyrate levels are associated with hair loss. Persistent respiratory symptoms correlated with opportunistic and pathogenic gut bacteria while neuropsychiatric symptoms and fatigue were linked with nosocomial gut pathogens such as Clostridia species and Actinomyces naeslundii. It’s worth also noting that Actinomyces is often found in water damaged buildings and may drive respiratory symptoms.  The gut also plays a role in modulating regulation of viral infections through interferon signalling.

Bloodwork often looks “normal”, until you look at subsets of natural killer cells and cytokine markers. GPs are not routinely checking for clotting markers so microclot formation is often missed in routine blood tests. Exercise intolerance is common. Muscle endurance is dramatically lower with markedly reduced aerobic capacity (VO2 max drops by around 20%), high blood oxygen levels at peak exertion which does not get taken up by the muscles as it should be, higher levels of oxygen in venous blood due to inefficient mitochondrial function, rapid and inefficient breathing removing too much co2 driving symptoms like fatigue and cognitive issues. We see the reactivation of viruses and stealth infections due to low levels of CD4 and CD89 cells which fight intracellular organisms. High levels of inflammatory cytokines drive other symptoms like joint and muscle pain, fatigue, and peripheral neuropathy. Autoimmune processes get triggered.

And what about long-term risk? COVID 19 has created significant neurological and neuropsychiatric complications both during acute illness and afterwards. Tau proteins and neurofilament levels, neuroinflammation increases. It is hypothesized that anosmia can be a sign of the virus reaching the brain via the olfactory nerve. A paper in Nature that came out two weeks ago discusses a long-term substantial rise in cardiovascular disease risk even after a mild case of COVID.  Many patients who experienced breathlessness during acute infection without needing hospitalisation will potentially have lung abnormalities.

And the mental health implications? COVID itself triggered severe and resistant depression for many of my patients and friends. The Guardian warned just yesterday of the increased risk of developing a mental health disorder post-COVID infection.

Strategies for Post-Acute COVID-19 Syndrome

I’m also seeing patients who have been to see other practitioners and been put on really aggressive treatment protocols. How can a depleted immune system cope with strong antimicrobial herbs or long courses antibiotics? Or ozone therapy? This is where things go horribly wrong and patients hit an impasse. Most PACS patients have digestive symptoms and poor mitochondrial function, immune dysregulation and high levels of oxidative stress. Basic foundational digestion and assimilation optimisation gets overlooked. This is key! How can you run your mitochondria properly without ensuring you have enough nutrient co-factors to run the cycle and also dampen down oxidative stress, run your liver pathways, and so on.I often provide a diagram of the Kreb’s cycle to patients so they understand that energy cannot be produced without certain nutrients, and if there are certain compounds blocking these cycles from running effectively. B vitamins are key, as is butyrate supplementation.

I find glutathione incredibly helpful, not just for its antioxidant properties, but as an antiviral. Glutathione and its precursor NAC are not something I can start my patients on straight away as most cannot tolerate sulphur compounds until we have started to address sulfidogenic bacteria in the gut and supported sulphur metabolism, methylation and mitigating excessive histamine production and release. The lungs have 120 times more glutathione than any other area of the body, and low levels of glutathione (either due to poor diet, lifestyle and high toxic load, or genetic SNPs) may increase risk of severe disease.

Quercetin is incredible. It interferes with the virus binding to cells so is also useful in acute COVID, and dampens down histamine release. None of my patients seem to find pharmaceutical antihistamines particularly effective and do better on natural anti-histamine compounds like quercetin, luteolin, diamine oxidase, tulsi, and butterbur. Melatonin is a powerful antioxidant and blocks inflammasome activity. Turmeric and St. John’s wort not only modulate the inflammatory response, but also have anti-viral and anti-depressant activity.

I use high doses of vitamin A, vitamin D, omega 3s and bovine immunoglobulins in clinic for their gut-healing, immunomodulatory, anti-inflammatory, antiviral, and antioxidant activity. EBV reactivation has been a factor in all my long COVID patients thus far, so this is also something that has to be addressed, along with any other stealth infections. Different infections cross-react with different foods, but gluten, dairy and egg often come up as problematic. Often medicinal mushrooms (which are amazing for their immunorestorative activity) are sadly problematic to supplement with for patients who have mould issues.

Hyperbaric oxygen helps to modulate immune response, improve oxygenation and dampen down oxidative stress, as well as helping to expedite tissue healing, especially where there is lung damage. Frequency specific microcurrent increases ATP production and can really make a big difference as part of a wider protocol.

We work on the mental health factors. When you suddenly lose the ability to be able to do what you did before, it can have a profound impact on your mental health. Herbal medicine is often not enough, and we need to supplement with targeted amino acids and good sleep support. Every patient is unique so there is no one blueprint.

References

Carfì, A., Bernabei, R., Landi, F., & Gemelli Against COVID-19 Post-Acute Care Study Group (2020). Persistent Symptoms in Patients After Acute COVID-19. JAMA, 324(6), 603–605. https://doi.org/10.1001/jama.2020.12603

Liu, Q., Mak, J., Su, Q., Yeoh, Y. K., Lui, G. C., Ng, S., Zhang, F., Li, A., Lu, W., Hui, D. S., Chan, P. K., Chan, F., & Ng, S. C. (2022). Gut microbiota dynamics in a prospective cohort of patients with post-acute COVID-19 syndrome. Gut, 71(3), 544–552. https://doi.org/10.1136/gutjnl-2021-325989

Nalbandian, A., Sehgal, K., Gupta, A., Madhavan, M. V., McGroder, C., Stevens, J. S., Cook, J. R., Nordvig, A. S., Shalev, D., Sehrawat, T. S., Ahluwalia, N., Bikdeli, B., Dietz, D., Der-Nigoghossian, C., Liyanage-Don, N., Rosner, G. F., Bernstein, E. J., Mohan, S., Beckley, A. A., Seres, D. S., … Wan, E. Y. (2021). Post-acute COVID-19 syndrome. Nature medicine, 27(4), 601–615. https://doi.org/10.1038/s41591-021-01283-z

Park, J. H., Cox-Ganser, J. M., White, S. K., Laney, A. S., Caulfield, S. M., Turner, W. A., Sumner, A. D., & Kreiss, K. (2017). Bacteria in a water-damaged building: associations of actinomycetes and non-tuberculous mycobacteria with respiratory health in occupants. Indoor air, 27(1), 24–33. https://doi.org/10.1111/ina.12278

Sidik S. M. (2022). Heart-disease risk soars after COVID – even with a mild case. Nature, 10.1038/d41586-022-00403-0. Advance online publication. https://doi.org/10.1038/d41586-022-00403-0

Singh, I., Joseph, P., Heerdt, P. M., Cullinan, M., Lutchmansingh, D. D., Gulati, M., Possick, J. D., Systrom, D. M., & Waxman, A. B. (2022). Persistent Exertional Intolerance After COVID-19: Insights From Invasive Cardiopulmonary Exercise Testing. Chest, 161(1), 54–63. https://doi.org/10.1016/j.chest.2021.08.010

Wirusanti, N. I., Baldridge, M. T., & Harris, V. C. (2022). Microbiota regulation of viral infections through interferon signaling. Trends in microbiology, S0966-842X(22)00007-5. Advance online publication. https://doi.org/10.1016/j.tim.2022.01.007