Advanced and Experimental Treatments for Taming Long COVID
There is no specific medication for the complex post-infectious condition termed Long COVID. But researchers are not idle. Neither are clinicians completely helpless in finding ways to treat and manage Long COVID. In Chapter 6, I outlined natural therapies that promote healing and speed recovery for this persistent condition. You can try most of those on your own. In this chapter, I discuss additional therapies useful in managing Long COVID, including:
- Mitochondrial Support: NAD+ IV and Coenzyme Q10
- Low-Dose Hormone Therapy: Cortisol, DHEA, and testosterone
- Combination Therapies: Nutritional supplement combinations and supplement-with-drug combinations, as well as drug-with-drug combinations
- Medical Devices: TENS
- Hyperbaric Oxygen and Inhaling Nitrogen
- Blood Irradiation: Ozone and ultraviolet light
- Immunological Therapies: SOT for chronic Epstein-Barr Virus
Most of these therapies require management by a physician and performed in a clinical setting. Let’s look at each of them to see what might be helpful for your case.
Mitochondrial Support: Intravenous NAD+ and Coenzyme Q10
NAD+ is the oxidized form of nicotinamide adenine dinucleotide. It is essential for energy production and regulating gene expression, DNA repair, and immune function. SARS-CoV-2 infection alters key metabolic and immunological processes. In a 2022 paper, researchers found that highly complicated immunometabolic processes deplete NAD+ levels in cells. NAD+ deficiency plays a role in several diseases, including an inadequate response to viral infection. Lower mitochondrial activity is also associated with ME/CFS and Long COVID.
NAD+ supplements improve mitochondrial function and response to viral infection. Though oral supplements of NAD help, the most effective way to increase your NAD+ level is by intravenous (IV) infusion. The standard dose is 750 mg, administered over 6 hours. One session per week for two months can replenish NAD deficiency.
Oral NAD as nicotinamide mononucleotide (NNM) is a safe, but only moderately effective way to boost your NAD+ level compared to IVs. NAD IVs plus supplements work best. I recommend InfiniWell’s NMN supplement. Take one 200 mg capsule daily.
Since NAD+ plays an essential role in cellular metabolism, knowing your blood level of NAD+ provides insight into your mitochondria’s health and biological age. However, standard clinical laboratories don’t test for NAD+ because it’s unstable in blood, so it’s difficult to measure accurately.
The custom laboratory, NADMED, measures four types of NAD and glutathione: NAD+, NADH, NADP+, NADPH, plus GSSG and GSH. You can do this NAD+ testing at home with a single drop of your blood. The lab facilities are in Finland. They don’t provide direct-to-consumer service, so your doctor must order the test.
Coenzyme Q10: CoQ10 is taken orally but can also be given as an intramuscular injection or by intravenous (IV) infusion. A 2016 paper established that IV CoQ10 crosses the blood-brain barrier and is the preferred route for Long COVID patients.
Oral CoQ10 has low bioavailability, requiring higher doses to be effective. A 2022 study found that 500 mg of CoQ10 daily for six weeks didn’t reduce Long COVID symptoms. However, higher doses are required because of its poor bioavailability when taken orally. I prescribe 400-800 mg twice daily.
Mitoquinol mesylate is another compound for mitochondrial health. A 2022 study described MitoQ as a “mitochondrial-targeted antioxidant” used to protect the mitochondria within cells. According to the authors, it can restore mitochondrial homeostasis. I recommend MitoQ 10 or 20 mg twice daily.
Hormone Replacement Therapies
Most Long COVID patients are adults. But a 2024 JAMA article states about 6 million children in the US live with symptoms of Long COVID. This section applies to adolescents and adults who require adequate levels of adrenal and sex steroid hormones for optimal wellness.
Cortisol and Adrenal Extract: In the previous chapter, I discussed the role of cortisol deficiency in developing Long COVID. However, taking too much hydrocortisone is counterproductive. High doses used to treat acute SARS and MERS caused more harm than benefit. Chinese studies in early 2020 found methylprednisolone effective in reducing deaths among hospitalized acute COVID patients due to its anti-inflammatory effect. However, subsequent negative experiences with these steroid drugs resulted in guidelines against the routine use of glucocorticoids. Contradicting the Chinese experience, in late 2020, the WHO recommended glucocorticoids for 7-10 days in critically ill patients.
Did the risks of Long COVID outweigh the benefits? A 2023 study found that hospitalized patients treated with a short course of corticosteroids had a significant protective effect on the development of Long COVID. However, further research is required to validate these results and find improved preventative and management strategies for post-COVID-19 syndrome.
Synthetic glucocorticoids can cause long-lasting disruption of the HPA axis. Adrenal function shuts down, so less cortisol is produced. The main symptom is severe persistent fatigue, much like patients with Long COVID. Some cases return to normal in time, but many need ongoing adrenal support.
Naturopathic doctors (ND) have long used low-dose natural cortisol to treat fatigue syndromes and promote recovery after prolonged illnesses, including chronic infections. I discussed this treatment in Chapter 6.
Low-Dose Hydrocortisone: Physicians (MD and DO) practicing integrative medicine may prescribe low-dose synthetic hydrocortisone like Cortef as an alternative to natural adrenal support. Even though low-dose hydrocortisone is a safe form of hormone replacement therapy, it can suppress the adrenal glands’ ability to make cortisol if taken for more than a few weeks. The standard dosage is 5 or 10 mg daily in the morning. When you stop using it, your cortisol level may be lower than before treatment. Short-term symptom improvement is not a good tradeoff at the cost of long-term health. Focus on supporting and restoring adrenal gland function over time.
Testosterone Replacement: A 2022 paper found that men with testosterone deficiency have higher levels of immune chemicals that support inflammation, including Interleukin-1, Interleukin-6, and Tumor Necrosis Factor-alpha. Testosterone deficiency is likely part of an endocrine-immunological signature that makes men’s response to chronic COVID different from women’s. It’s not clear if testosterone deficiency makes Long COVID fatigue worse or if it’s simply a bystander in a subset of male patients. Many older male Long COVID patients have age-related testosterone deficiency and may benefit from low-dose testosterone replacement.
However, there are no standard guidelines for treating testosterone deficiency in male Long COVID patients. Before starting testosterone replacement, test for total and free testosterone in a blood sample. The LabCorp reference range for men is 264-916 ng/dL. Below 250 ng/dL is deficient and needs to be improved. But even 300 ng/dL can indicate deficiency in some men, especially if they have symptoms of low testosterone. In my practice, I aim for 400-450 ng/dL for men over 65 years, and 750-900 ng/dL in younger men.
Symptoms of Testosterone Deficiency:
- Low or absent sex drive.
- Erectile dysfunction.
- Loss or thinning of body hair and beard.
- Loss of lean muscle mass or difficulty building stronger muscles.
- Constant fatigue without being overworked or overexercised.
- Easy to gain weight or difficulty losing weight.
- Low mood and lack of motivation.
Treating testosterone deficiency requires a topical gel, cream, or injections. An average dosage for testosterone cypionate intramuscular injection is 50-100 mg once a week. Topicals are applied daily. An average starting dose is 5 mg once daily. During the first year, check your testosterone level with a blood test every three months. Adjust your dosage according to your doctor’s recommendation based on the test results and as your symptoms improve.
Combination Therapies
Combining one or more treatments can have synergistic effects and improve outcomes. Combinations of nutritional supplements and hormones, supplements with drugs, and drugs with other drugs may work better than individual medications alone.
Examples of Supplement Combinations:
- Oral NAC and Glutathione
- Intravenous Glutathione and NAC Nebulizer
Supplement and Drug Combinations:
- Antiviral drugs and NAC—A 2023 paper found that N-acetylcysteine (NAC) reduced the severity of symptoms in acute COVID patients. Antivirals can lower viral load, and NAC improves respiratory function.
- Guanfacine and NAC—A 2023 study found that combining guanfacine and NAC helped lift brain fog. Guanfacine is a prescription drug used for high blood pressure and has benefits for those with attention-deficient hyperactivity disorder (ADHD).
- NAD+ and Low-Dose Naltrexone—A 2024 study found low-dose naltrexone (LDN) with NAD+ lessened Long-term COVID fatigue.
- Remdesivir and Linoleic Acid (LA)—Nature fatty acids (FAs), including linoleic acid (LA), have broad antiviral activity. FAs exert a wide range of biological activities, including reducing inflammation in lung tissue. Remdesivir has broad-spectrum activity against many viruses, including SARS and MERS, but it was not as effective against SARS-CoV-2. However, the remdesivir-LA combination reduced side effects and improved its inhibition of SARS-CoV-2.
Drug-Drug Combinations: The Patterson Protocol (Maraviroc and Pravastatin)
Bruce Patterson, MD, was a proactive voice in the early months of the COVID-19 Pandemic. He’s now working on a solution to Long COVID. In overly simplified terms, Patterson contends that the persistence of the S1 spike protein in monocytes causes immune dysregulation, which drives symptoms of the post-viral condition. He came up with the 2-drug combination, maraviroc and pravastatin, as a form of precision medicine targeting S1.
Maraviroc is an anti-HIV drug that blocks HIV from entering cells by selectively binding to a chemokine receptor on the cell membrane. Pravastatin is a drug used to treat high LDL cholesterol. It works by inhibiting an enzyme in the liver, HMG-CoA reductase, that makes cholesterol. The combination of maraviroc and pravastatin interrupts the monocyte-endothelial-platelet axis, helping restore immune function in post-COVID illness.
Dr. Patterson’s lab company, IncellDx, will provide testing for Long Haulers in Europe in the fall of 2024. Listen to Dr. Patterson explain his research to Dr. Syed in 2024.
Medical Devices
Repositioning commonly used medical devices may have a role in managing COVID. However, they don’t address the fundamental causes of Long COVID. The advantage is that you can do them independently at home, avoiding the stress of getting to a medical center for treatments.
- Red-Light Therapy
Red light therapy (RLT), or photobiomodulation therapy, uses low-wavelength red light to reduce inflammation and promote tissue healing. Red light may be applied to large body areas, like over the lungs for respiratory symptoms, the whole body while sitting in a cabinet, or to specific body areas or acupuncture points using a low-level, red-light laser.
Natural photobiomodulation is as simple as getting out in the sunshine. It may lift mood and improve energy. To learn more, listen to Dr. Roger Seheult on YouTube.
- TENS Machine
A 2023 study found that muscle stimulation and TENS can improve lung function, improving SpO2. TENS therapy is used for chronic pain. It is a small, battery-operated device about the size of a cell phone that delivers electrical stimulation to muscles and nerves.
- Vagal Tone Stimulation
The vagus nerve carries crucial bioelectrical signals from the brain to the body’s organs. Yoga, meditation, and slow breathing practices have a positive influence on the vagus nerve, soothing an overly active adrenal response and resulting in feeling calmer, centered, and rested.
In an examination of autopsies on some patients who died from COVID, researchers found viral RNA and inflamed cells in vagal tissue. This suggests that SARS-CoV-2 can damage the vagus nerve, dampening vagal tone, a fundamental action of the parasympathetic nervous system. In a 2023 study, researchers found vagus nerve inflammation common in acute COVID. An inflamed vagus nerve leads to dysautonomia – the abnormal function of the autonomic nervous system. Symptoms of dysautonomia are like those experienced by Long COVID patients, including fatigue, brain fog, palpitations, shortness of breath, and lightheadedness without fainting.
Acupuncture and auricular acupuncture regulate the vagus nerve. I discussed acupuncture’s benefits in a previous chapter. Researchers believe improvement in ME/CFS and Long COVID patients receiving acupuncture is due to restoring vagal nerve tone.
Improved vagal tone promotes calmness. Support vagal tone with yoga and tai chi, deep breathing practices, and eating regular meals to prevent hypoglycemia and stay hydrated.
Oxygen and Hydrogen Therapies
Hyperbaric Oxygen Chambers: Hyperbaric oxygen therapy (HBOT) involves reclining in a sealed chamber and breathing pure oxygen under three times normal pressure. It has a long history for scuba divers with decompression sickness. HBOT helps speed up wound healing and enhances stroke recovery. But can it improve Long COVID symptoms?
Several studies have found benefits of using HBOT for long haulers. A 2022 study found it induced neuroplasticity, stimulated stem cells, improved mitochondrial activity, and encouraged the growth of new vascular tissue.
Inhaled Hydrogen Therapy: Molecular hydrogen (H2) is an antioxidant with specific free-radical scavenging properties and anti-inflammatory effects. H2 modulates the nuclear factor erythroid-related factor 2 (Nrf2) pathway, considered the master regulator of antioxidant homeostasis. It reduces inflammation and helps maintain cell functional integrity. Natural Nrf2 compounds include plant-based antioxidants, such as green tea extract, oleuropein from olive leaf, and sulforaphane from cabbage family vegetables. Hydrogen therapy is safe to use daily.
Oxygen-Ozone Therapies: Traditional nature cure doctors, like Bernard Jensen, said all diseases originate in the blood. The treatment was absolute rest, fasting, plenty of pure water, and concentrated fresh vegetable juices. Over time, the body self-cleanses. When blood is renewed, tissues heal. Modern ways to clean the blood include:
- Irradiating it with ultraviolet light.
- Exposing it to ozone.
- Using apheresis technology to filter harmful substances, including viruses, from the blood.
Oxygen-Ozone Therapies: Traditional nature cure doctors, like Bernard Jensen, said all diseases originate in the blood. The treatment was absolute rest, fasting, plenty of pure water, and concentrated fresh vegetable juices. Over time, the body self-cleanses. When blood is renewed, tissues heal. Modern ways to clean the blood include:
- Irradiating it with ultraviolet light.
- Exposing it to ozone.
- Using apheresis technology to filter harmful substances, including viruses, from the blood.
Ozone and Ultraviolet Blood Irradiation: These clinical therapies improve quality of life by purifying the entire blood system. They can treat peripheral vascular disease and chronic infections like Lyme disease.
Extracorporeal blood oxygenation and ozonation (EBOO) is a form of dialysis designed to filter and expose blood to ozone. It treats toxicity and chronic illnesses, including chronic Lyme disease. It employs a filter to clean the blood of heavy metals and then exposes it to ozone, which eliminates bacteria and viruses. One EBOO session takes about four hours and can detoxify several liters of blood.
INUSpheresis is an advanced form of photobiomodulation apheresis therapy used to treat autoimmune diseases and ME/CFS patients. A 2023 paper describes the practice and results of lowering specific biomarkers of inflammation, including interleukin-6 and C-reactive protein, in Long COVID patients. The technology is German, and clinics are in Germany and Greece.
Light Therapies and Photobiomodulation: Low-level laser therapy involves projecting concentrated light to stimulate immune activity, promote tissue repair, decrease inflammation, and control pain. Theoretically, mitochondria can absorb red to near-infrared light to increase adenosine triphosphate (ATP), the cell’s energy currency. This stimulates several biochemical pathways that impact protein synthesis, anti-inflammatory activity, and ATP production.
In a 2023 Brazilian study, researchers used laser acupuncture to treat fatigue in COVID patients during the early recovery phase of the disease who experienced severe post-COVID fatigue. All patients noted improvement in their breathing patterns, including the ability to take deeper breaths and less chest pain.
Intravenous Immunoglobulin (IVIG): IVIG is an immunomodulatory therapy consisting of human antibodies from healthy donors. It was highly effective in the early months of the Pandemic. For Long-Term COVID, IVIG targets the inflammatory and autoimmune activity associated with SARS-CoV2 neuropathy, not as an antiviral but as an immune-regulating therapy. It helps upregulate T-cells that defend against viruses and inhibit B-cells related to a worsening condition. A 2023 review paper found that some patients, even in an advanced state of chronic COVID, improved with IVIG infusions.
SOT Antiviral Serums: Antisense therapy, using nucleic acid-based oligonucleotides termed short oligonucleotide therapy (SOT), is used in Europe to treat cancer, viral infections, and genetic disorders. The mechanism of action is through RNA-mediated interference (RNAi), where short double-stranded RNA (dsRNA) molecules cause messenger RNA (mRNA) degradation. RNA interference is a physiological process required for the regulation of gene expression. Positive gene expression supports health.
No SARS-CoV-2 SOT serums are available for clinical use. However, Epstein-Barr SOT is available. One theory of the cause of Long COVID is the reactivation of EBV. Chronic EBV is also associated with ME/CFS. To be clear, it’s not chronic-active Epstein-Barr virus (CAEBV). Symptoms in chronic-active EBV include high fever, tender swollen light nodes, and an enlarged spleen. Although chronic Long COVID patients can feel warm and have a periodic low-grade temperature, they do not have a high fever. And they often don’t have swollen lymph glands. These are physical signs of the body’s aggressive immune response to an active infection.
Quest and Labcorp have EBV profiles that test for active or chronic infection.
| Infection | VCA lgM | VCA lgG | EA | EBNA |
| None | Negative | Negative | Negative | Negative |
| Acute or Primary | Positive | Positive | Positive or Negative | Positive or Negative |
| Recent | Positive or Negative | Positive | Positive or Negative | Positive or Negative |
| Past | Negative | Positive | Negative | Positive |
| Reactivation | Positive or Negative | Positive | Positive | Positive |
Also, test for the EBV viral load by quantitative PCR. Viral load defines actual EBV virions present and estimates the number of viruses in a blood sample. EBV is the abbreviation for Epstein-Barr Virus. VCA is for viral capsid antigen. EA is for early antigen and EBNA is Epstein-Barr nuclear antigen. IgM is immunoglobulin M present in acute infection. IgG is immunoglobulin G present in chronic infection.
| EBV DNA, Quant PCR, Plasma | Results | Flag | Units | Reference Range |
| None Detected | Negative | None | IU/mL | 35-100,000,000 IU/mL |
EBV (Epstein-Barr Virus) is a DNA virus in the Herpes virus family. Its acute form is infectious mononucleosis. The chronic form was once considered benign. It can cause swollen lymph nodes, low-grade fever, sore throat, and persistent fatigue. EBV DNA Quantitative PCR is also called the viral load, an estimate of the number of virions.
Conclusions
In my forty years of clinical practice, I haven’t seen as much scientific interest and clinical activity about a viral disease since the global AIDS epidemic in the early 1980s and chronic hepatitis C (HCV) in 1989. HIV and HCV patients are now well-managed, but not cured, with antiviral drugs. But Long COVID is not AIDS or chronic HCV. As yet, we don’t have an effective, specific antiviral for SARS-CoV-2.
Symptoms of Long COVID are similar, with many overlaps, to ME/CFS. However, chronic fatigue syndrome (CFS) has been an ignored stepchild condition since the first cases in the mid-1980s that emerged in Lake Tahoe, California. For years, it was not even categorized as a real disease with its own ICD diagnostic code. It wasn’t until 2015 that the Institute of Medicine published a report establishing new diagnostic criteria that described ME/CFS as a “serious, chronic, complex systemic disease.”
There is no “cure” for ME/CFS or Long COVID. However, there are effective and safe ways to manage this condition. In many cases, there are ways to reduce symptoms while navigating the course of the disease and, eventually, helping patients return to health.
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