Long COVID and LDN

Are you struggling with long COVID and looking for new ways to manage its lingering symptoms? You’re not alone. Millions of people are experiencing long COVID, a condition where symptoms like fatigue, brain fog, and muscle pain persist long after the initial infection. One promising treatment gaining attention is low-dose naltrexone (LDN). In this blog post, we dive into how LDN works, its potential to reduce inflammation, and its role in regulating the immune system to help alleviate long COVID symptoms.

We’ll explore the science behind LDN, its success in treating conditions like chronic fatigue syndrome and fibromyalgia, and why it’s becoming a popular option for long COVID treatment. Read on to discover if LDN could be the breakthrough you’ve been waiting for in your journey to recovery.

Long COVID

Many people who recover from COVID-19 still experience lingering symptoms long after the infection is gone [1]. This condition, known as long COVID, lasts for at least 3 months after the initial illness and can show up as ongoing, recurring, or even worsening symptoms that affect the whole body  [1] . Common issues include fatigue, brain fog, shortness of breath, and other health problems  [1].

How many people have long COVID?

Long COVID affects about 10% to 30% of those infected. It can happen to anyone—even those who had mild or no symptoms at first—but is more common in people who were seriously ill [2]. The condition can also make existing health problems worse and significantly disrupt daily life, putting extra pressure on healthcare systems worldwide.

Long COVID and brain fog

One major aspect of Long COVID is neuro-long COVID, which involves cognitive problems and fatigue, often called “brain fog” [3]. Up to 30% of patients have trouble with thinking, and nearly 46% report memory issues [3]. These cognitive difficulties can last for months or even years, making long-term care and specialized treatments essential.

What causes long COVID?

Long COVID seems to be caused by many factors working together. Scientists think that issues like an overactive immune system, problems with the cell’s power plants (mitochondria), blood vessel damage, ongoing inflammation, autoimmunity, lingering virus, nervous system issues, and imbalances in the body’s microbes all play a role [3].

Persistent immune system activation

One key problem is that the immune system stays activated for months after the infection, which might prevent the body from returning to normal. This means that certain components of the immune system remain in a prolonged “on” state, such as the innate immune system, this is part of the immune system that behaves as the first responders.

While, other elements of the immune system become exhausted due to the prolonged activation, such as the T cells of the more specialised adaptive immune system. Then there are the lingering chemical messengers, interferons, which keep the immune system on high alert [4].

Mitochondrial dysfunction and long COVID

Problems with mitochondria—possibly triggered by dormant viruses like Epstein-Barr—can lead to low energy, chronic fatigue, and difficulty with exercise [5].

Damaged blood vessels and long COVID

Additionally, damage to blood vessels can cause small clots and poor oxygen delivery, which might increase the risk of heart and blood vessel issues, such as deep vein clots and lung clots [6].

Low-dose naltrexone and long COVID

Numerous studies have reported that low-dose naltrexone or LDN have improved long COVID symptoms, especially fatigue, post-exertional malaise and pain [7].

For example, one study of 38 long COVID patients found that over two months, many experienced less pain, better mood, and reduced joint pain and chest tightness [8].

In another study, 59 patients, those who took LDN reported fewer symptoms, especially improvements in fatigue, post-exertional malaise, unrefreshing sleep, and abnormal sleep patterns. Importantly, the length of time someone had symptoms (whether more or less than a year) did not seem to affect how well LDN worked [7].

What is low-dose naltrexone?

Naltrexone is a well-known drugs that block opioids. When given in doses much lower than the usual 50mg, it works in different ways. For example, low-dose naltrexone (LDN), usually 1 to 4.5 mg per day, can reduce inflammation in the brain by affecting certain immune signals and also temporarily boosts the body’s natural opioid system.

Some reports suggest LDN may help with conditions like fibromyalgia, Crohn’s disease, multiple sclerosis, complex regional pain syndrome, long COVID and even cancer [9].

The right and left hands of naltrexone

Just like with have two hands which are identical but cannot be superimposed on one another, certain drugs also possess the properties of  “handiness”. This ability of a drug molecule to exist either as a left hand (levo) or right hand (dextro) version is known as chirality.

The name of many drugs gives this phenomena away, for example, levothyroxine and levocetirizine. Usually either the levo or dextro form of the drug is active, with the other version causing unwanted side effects [10].

However, with naltrexone both the left hand (levo) and the right hand (dextro) versions have positive effects on the body.

Dextro-naltrexone effects

The dextro naltrexone form targets toll-like receptors (TLRs), which are found on immune cells like microglia, mast cells, and macrophages. By blocking these receptors, dextro naltrexone reduces the production of substances that cause inflammation and stops the inflammatory chain reaction.

Levo-naltrexone effects

On the other hand, the levo form affects opiate receptors—the ones that natural endorphins use. It temporarily blocks these receptors, which then triggers the body to produce more anti-inflammatory endorphins and increases the number of opiate receptors. This form also directly influences how some cells grow.

How does low-dose naltrexone work?

Low-dose naltrexone (LDN) has been used for years to treat a variety of conditions. It works by directly affecting the disease and by changing how the immune system functions.

Because many illnesses are linked to immune system problems, LDN has become a popular treatment option. It’s even being considered to help with long COVID symptoms, and there’s good scientific reason for this.

LDN as an anti-inflammatory

LDN is known for its strong anti-inflammatory effects—it helps lower inflammation in the body. Lab studies have shown that LDN can change the way certain immune cells work, reducing the release of inflammatory chemicals called cytokines, which act as messengers to activate the immune system.

Low-dose naltrexone reduces cytokine levels

In patients taking LDN, levels of key cytokines (like G-CSF, IL-4, IL-6, IL-10, IFN-alpha, and TNF-beta) dropped significantly after eight weeks. This ability to reduce inflammation supports the growing view that low-dose naltrexone or LDN helps regulate the immune system.

Recent studies show that LDN affects the TLR-9 pathway, which can lower levels of IL-6—a key chemical that drives inflammation, especially in COVID.

Opioids and the immune system

Even though we don’t fully understand how naltrexone—a drug that blocks opioids—changes immune chemicals (cytokines), we do know that opioids like morphine can weaken the immune system.

This is because immune cells have opioid receptors that help control immunity.

Long COVID and similarities with chronic fatigue syndrome

LDN is already accepted as a useful treatment for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and fibromyalgia, both of which share some symptoms with long COVID.

There is a significant overlap between ME/CFS and PASC symptoms [11]. In a cohort of 140 patients with PASC, 46 % also met the diagnostic criteria for ME/CFS [12].

Who can benefit from LDN?

Because long COVID can vary a lot from person to person, it might be most helpful for those with symptoms similar to chronic fatigue syndrome (ME/CFS)—such as severe fatigue, unrefreshing sleep, cognitive issues, and difficulty standing.

About half of long COVID patients show these symptoms, and studies in non-COVID ME/CFS patients have shown that LDN can help nearly 74% of them [13]. In that study, most patients reported feeling more alert and showed improvements in both physical and mental performance. Some even experienced less pain and fever, with no serious side effects or long-term issues [13].

Summary of long COVID and LDN

 The use of LDN was associated with a fewer number of symptoms, improved clinical symptoms (fatigue, post-exertional malaise, unrefreshing sleep, and abnormal sleep pattern), and a better functional status. 

LDN FAQs

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If you have long COVID and are unsure what steps to take, book a FREE consultation with one of our prescribers. They will guide you to the best evidence-based treatments and can even recommend bespoke compounded solutions.

To get in touch, email info@medicalmojo.co.uk or call 023 8157 5111

Disclaimer: This article is for informational purposes only and is not a substitute for professional medical advice.

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References:

1. Ely, E.W., Brown, L.M. and Fineberg, H.V., 2024. Long covid defined. New England Journal of Medicine, 391(18), pp.1746-1753.
2. Fesharaki-Zadeh, A., Lowe, N. and Arnsten, A.F., 2023. Clinical experience with the ?2A-adrenoceptor agonist, guanfacine, and N-acetylcysteine for the treatment of cognitive deficits in “Long-COVID19”. Neuroimmunology Reports, 3, p.100154.
3. Dietz, T.K. and Brondstater, K.N., 2024. Long COVID management: a mini review of current recommendations and underutilized modalities. Frontiers in Medicine, 11, p.1430444.
4. Phetsouphanh, C., Darley, D.R., Wilson, D.B., Howe, A., Munier, C., Patel, S.K., Juno, J.A., Burrell, L.M., Kent, S.J., Dore, G.J. and Kelleher, A.D., 2022. Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection. Nature immunology, 23(2), pp.210-216.https://www.nature.com/articles/s41590-021-01113-x
5. Guntur, V.P., Nemkov, T., de Boer, E., Mohning, M.P., Baraghoshi, D., Cendali, F.I., San-Millán, I., Petrache, I. and D’Alessandro, A., 2022. Signatures of mitochondrial dysfunction and impaired fatty acid metabolism in plasma of patients with post-acute sequelae of COVID-19 (PASC). Metabolites, 12(11), p.1026.
6. Charfeddine, S., Ibn Hadj Amor, H., Jdidi, J., Torjmen, S., Kraiem, S., Hammami, R., Bahloul, A., Kallel, N., Moussa, N., Touil, I. and Ghrab, A., 2021. Long COVID 19 syndrome: is it related to microcirculation and endothelial dysfunction? Insights from TUN-EndCOV study. Frontiers in cardiovascular medicine, 8, p.745758.
7. Bonilla, H., Tian, L., Marconi, V.C., Shafer, R., McComsey, G.A., Miglis, M., Yang, P., Bonilla, A., Eggert, L. and Geng, L.N., 2023. Low-dose Naltrexone use for the management of post-acute sequelae of COVID-19. International immunopharmacology, 124, p.110966.
8. O’Kelly, B., Vidal, L., McHugh, T., Woo, J., Avramovic, G. and Lambert, J.S., 2022. Safety and efficacy of low dose naltrexone in a long covid cohort; an interventional pre-post study. Brain, Behavior, & Immunity-Health, 24, p.100485.
9. Toljan, K. and Vrooman, B., 2018. Low-dose naltrexone (LDN)—review of therapeutic utilization. Medical Sciences, 6(4), p.82.
10. Nguyen LA, He H, Pham-Huy C. Chiral drugs: an overview. Int J Biomed Sci. 2006 Jun;2(2):85-100.
11. Chen, C., Haupert, S.R., Zimmermann, L., Shi, X., Fritsche, L.G. and Mukherjee, B., 2022. Global prevalence of post-coronavirus disease 2019 (COVID-19) condition or long COVID: a meta-analysis and systematic review. The Journal of infectious diseases, 226(9), pp.1593-1607.
12. Bonilla, H., Quach, T.C., Tiwari, A., Bonilla, A.E., Miglis, M., Yang, P.C., Eggert, L.E., Sharifi, H., Horomanski, A., Subramanian, A. and Smirnoff, L., 2023. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome is common in post-acute sequelae of SARS-CoV-2 infection (PASC): Results from a post-COVID-19 multidisciplinary clinic. Frontiers in neurology, 14, p.1090747.
13. Polo, O., Pesonen, P. and Tuominen, E., 2019. Low-dose naltrexone in the treatment of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Fatigue: Biomedicine, health & behavior, 7(4), pp.207-217.