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Metformin for long COVID
METFORMIN
What is metformin?
Metformin is a first-line agent used in the treatment of Type II diabetes. It helps lower blood sugar by decreasing the amount of blood sugar made in the liver and decreasing the amount of blood sugar absorbed by the gastrointestinal tract.
How can metformin impact long-COVID?
Although used for diabetes, there has been some research conducted to look at its effects on those with long-COVID. A recent long-COVID study showed that 6.2% of patients using metformin received a long-COVID diagnosis compared to 10.3% of patients not using metformin [1]. This study included pregnant and lactating patients and people between the ages of 30-85. The mechanism by which this occurs is multifold. It is thought metformin possesses anti-inflammatory and antithrombotic effects in addition to its impact on blood sugar. Additionally, it is theorized that metformin can assist in stopping part of the replication process of the COVID-19 virus, thus leading to its death inside the body [2].
Although current guidelines do not support metformin’s use in the treatment of long-COVID, further clinical studies may warrant its use for those suffering from symptoms of long-COVID.
References:
1https://covid19.nih.gov/news-and-stories/can-diabetes-treatment-reduce-risk-long-covid
Active Clinical Trials: Long COVID, metformin | Card Results | ClinicalTrials.gov
Pyridostigmine for long COVID
PYRIDOSTIGMINE
What is pyridostigmine (Mestinon)?
Pyridostigmine is a medication used to treat myasthenia gravis. Myasthenia gravis causes voluntary muscles to feel weak and tire quickly [1]. Muscles in the body use a substance called acetylcholine to contract. Without acetylcholine to excite the muscle, it stays limp. Pyridostigmine works to inhibit the breakdown of acetylcholine, leaving it available for the muscles to use.
Does pyridostigmine play a role in long-COVID?
Patients diagnosed with long-COVID can experience lightheadedness, postural orthostatic tachycardia syndrome (POTS), chest pain, and a fast heartbeat. To manage symptoms, several clinicians have turned to pyridostigmine as a treatment option. As some patients have fast heartbeats, pyridostigmine can help regulate them by allowing the acetylcholine to stay in the area where the cells can use it. Pyridostigmine has been mentioned to help control POTS in studies and hospital formulary guidelines [2,3].
Additionally, pyridostigmine may affect the chronic fatigue many long-COVID patients experience. According to one researcher, pyridostigmine can trigger the release of norepinephrine, the molecule responsible for mood and alertness. Activating norepinephrine propels blood back to the heart, supplies the muscles with more blood, and increases oxygen supply, leaving a person less fatigued [4].
Pyridostigmine is not a cure for long-COVID and will not eradicate it from the body. However, its use in POTS is well known and may offer symptom management for those suffering from long-COVID effects.
References:
1https://www.mayoclinic.org/diseases-conditions/myasthenia-gravis/symptoms-causes/syc-20352036
3https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146298/
Anti-inflammatory diet for long COVID
ANTI-INFLAMMATORY DIET
What is an anti-inflammatory diet?
An anti-inflammatory diet consists of foods that reduce inflammation and can help with high cholesterol, blood pressure, and blood sugar. Some specific food types with anti-inflammatory or antioxidant properties include omega-3 fatty acids found in fish such as salmon, tuna, and nuts; vitamin C in citrus fruits and vegetables; polyphenols found in berries, dark chocolate, and coffee; and fiber-rich foods such as asparagus and bananas.1
Two commonly considered anti-inflammatory diets are the Mediterranean diet and the DASH (Dietary Approaches to Stop Hypertension) diet. Both aim to reduce the amount of processed foods in your diet. The Mediterranean diet is primarily plant-based and consists of vegetables, fruits, fish, whole grains, beans, nuts and seeds, eggs, and olive oil. Moderate portions of dairy are included with options such as skim or 1% milk and low-fat Greek or plain yogurt. Red meat or processed meat is limited in this diet. The goal is to eat two to three servings of fruit and four or more servings of vegetables daily.2
The DASH diet is specifically designed to help prevent or lower blood pressure and cholesterol. It consists of foods rich in potassium, calcium, and magnesium, such as vegetables, fruits, whole grains, fish, low-fat dairy products, beans, and nuts, like the Mediterranean diet. The DASH diet focuses on limiting salt intake to 2,300 mg a day or even 1,500 mg a day.3 This diet also reduces alcohol and caffeine intake to lower blood pressure.
How can an anti-inflammatory diet help alleviate certain long COVID symptoms?
It is believed that long COVID symptoms may be due to a continuously hyperactive immune system even after the infection has passed, leading to a high inflammatory state. An anti-inflammatory diet can lessen the effects of the elevated inflammatory mediators in the body to help mitigate some long COVID symptoms. Foods in the Mediterranean and DASH diet have anti-inflammatory, antioxidant, and anti-thrombotic (or anti-clot forming) properties that help against cardiovascular disease and can address long COVID symptoms such as muscle and joint pains, sleep quality, and mood disorders such as depression.4
What evidence supports the use of an anti-inflammatory diet for long COVID?
There is growing evidence that COVID alters the gut microbiome and can result in more significant colonization of inflammation-associated bacteria. As a result, anti-inflammatory diets can aid in relieving symptoms caused by changes in the gut microbiome.5 Adherence to an anti-inflammatory diet has been negatively associated with COVID infections and may also reduce the length of hospital stays for COVID patients over 65 years old.6 Polyphenols and antioxidants in plant-based diets are associated with beneficial impacts on cognitive and mental health. In addition, a plant-based diet has demonstrated improved musculoskeletal pain and pain from osteoarthritis, rheumatoid arthritis, and chronic fibromyalgia.4 Omega-3 fatty acids and unsaturated fats may be beneficial in post-COVID depression; however, trial results are inconclusive.7
What are some things to watch out for with an anti-inflammatory diet?
Certain components of an anti-inflammatory diet, such as nuts, fish, and shellfish, can be allergens for certain people. Thus, these individuals may have challenges adhering to this diet. Because the anti-inflammatory diet reduces dairy intake, it is important to supplement calcium and vitamin D in other ways to prevent a deficiency.
References:
1) Snead L. Anti Inflammatory Diet. Johns Hopkins Medicine. Accessed November 2, 2023. https://www.hopkinsmedicine.org/health/wellness-and-prevention/anti-inflammatory-diet
2) Mayo Clinic Staff. Mediterranean diet for heart health. Mayo Clinic. Accessed November 2, 2023. https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/in-depth/mediterranean-diet/art-20047801#:~:text=Plant%20based%2C%20not%20meat%20based&text=That%20means%20meals%20are%20built,only%20once%20in%20a%20while
3) Mayo Clinic Staff. DASH diet: healthy eating to lower your blood pressure. Mayo Clinic. Accessed November 2, 2023. https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/in-depth/dash-diet/art-20048456
Active CVID Trials: Long COVID, inflammatory diet | Card Results | ClinicalTrials.gov
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Methylphenidate for long COVID
METHYLPHENIDATE
What is methylphenidate, and how does it work?
Methylphenidate is a stimulant medication that belongs to the drug class amphetamines. This medication acts on the central nervous system (CNS) by increasing levels of two chemicals, dopamine and norepinephrine, in the brain. Norepinephrine is thought to play a role in the body’s stress response and helps to regulate sleep, alertness, and blood pressure. Dopamine plays a crucial role in movement and affects motivation, perception of reality, and the ability to experience pleasure [1]. By increasing these levels of chemicals, it leads to an increase in focus and attention. Methylphenidate is a controlled substance and does have the potential for abuse if used in a manner inconsistent with how it is prescribed.
How can methylphenidate be used in long-COVID?
Sufferers of long-COVID often deal with “brain fog,” a persistent cognitive defect resulting in memory problems, poor focus, and decreased ability to concentrate. Although the reasoning is still unclear, researchers think COVID-19 may linger in the brain for months afterward. Even though it does not cause an active infection, it is a foreign substance in the body. This leads to constant attack by the immune system, causing inflammation. Over time, the continuous inflammation manifests as “brain fog” symptoms [2].
Stimulants, such as methylphenidate, can improve focus, attention span, and even fatigue. A case study completed in 2022 showed benefits when methylphenidate and other agents were used to help reduce “brain fog” [3]. Although no formal studies have been conducted on using methylphenidate for “brain fog,” one provider stated he has been using it, in conjunction with behavioral exercises, as a treatment option. He saw improved memory, attention, and concentration difficulties [4].
The chronic fatigue many patients face may be mitigated using methylphenidate as well. A study found that treatment with methylphenidate was significantly better than placebo in 17% of patients regarding their fatigue symptoms [5]. Although current recommendations do not advocate for the use of stimulants to treat long-COVID or symptoms of long-COVID, for those suffering from “brain fog” or fatigue, it may be an attractive option to those looking for symptom management.
References:
1https://americanaddictioncenters.org/antidepressants-guide/ndris#
3https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10102822/
4https://www.ohsu.edu/sites/default/files/2023-02/PCR23-Mon-18-AndersonWM.pdf
5https://pubmed.ncbi.nlm.nih.gov/16443425/
Remdesivir for long COVID
REMDESIVIR
What is remdesivir (Veklury)?
Remdesivir is an intravenous (IV) medication used to treat COVID-19. It was approved in 2020 and can be used in adults and children (over 28 days old and weighing at least 3 kilograms) [1]. Remdesivir is a nucleotide analog that works by inhibiting the process COVID-19 uses to replicate. This helps keep viral levels low so the body’s immune system has a chance to fight it off. It is best used within seven days of the start of symptoms [2].
Can remdesivir help with long-COVID?
Currently, remdesivir is only indicated for the treatment of COVID-19. However, research has been dedicated to exploring whether the use of remdesivir decreases the risk of contracting long-COVID. The results of these studies have been mixed. One study looked at patients two years after using remdesivir and found no effect on long-term recovery, quality of life, or long-COVID symptoms. Roughly one in four patients reported fatigue, and one in six felt their recovery from COVID-19 was incomplete. There were downfalls to this study; specifically, their sample population was small, leading to a large amount of uncertainty regarding the results [3]. A second study of remdesivir found treatment reduced long-COVID symptoms for at least six months [4]. Further, additional research showed patients receiving antiviral drugs (such as remdesivir) were less likely to develop long COVID than untreated participants [5].
There are mixed reviews concerning the use of remdesivir in preventing long-COVID, so it is difficult to determine whether it has a true benefit. For those already diagnosed with long-COVID, there has been no evidence to date that it could be a viable treatment option for eradication or symptom management of COVID-19.
References:
1https://www.gilead.com/-/media/files/pdfs/medicines/covid-19/veklury/veklury_pi.pdf
2https://www.nhs.uk/medicines/remdesivir-veklury/common-questions-about-remdesivir/
3https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9579198/
4https://pubmed.ncbi.nlm.nih.gov/34850210/
5https://www.contagionlive.com/view/can-early-outpatient-treatment-reduce-the-risk-of-long-covid-
Active Clinical Trials: Long COVID, remdesivir | Card Results | ClinicalTrials.gov
Cannabidiol (CBD) for long COVID
CANNABIDIOL (CBD)
What is cannabidiol?
CBD is an active ingredient found in the cannabis plant that does not contain THC (the component of marijuana that produces a high). According to the 2018 Farm Bill, hemp-derived products that are less than 0.3% THC are federally legal; therefore, CBD is considered legal at the federal level, but individual states may have different regulations. The FDA has currently approved one CBD product (Epidiolex), which is an oral solution that can be prescribed for certain types of epilepsy, such as Lennox-Gastaut syndrome and Dravet syndrome. CBD products can come in many forms and strengths, such as capsules, oil solutions, sublingual formulations, and sprays.
How can cannabidiol help alleviate certain long COVID symptoms?
In vitro, cannabidiol is a potent inhibitor of the SARS-CoV-2 virus. It has been suggested that CBD activates the interferon pathway, an antiviral component of the immune response that prevents viral replication, which leads to the degradation of viral RNA and subsequently prevents the release of cytokines (small proteins released by the body that can promote an inflammatory response).1
An analysis done by the University of Chicago on 1,212 patients showed that patients taking a prescribed oral solution of CBD for the treatment of epilepsy tested positive for COVID at significantly lower rates than matched patients who did not take CBD.2 This is believed to be due to the antiviral and anti-inflammatory effects of CBD.
Long COVID is believed to result from a prolonged hyperinflammatory state caused by dysregulation in the immune system. CBD can also cross the blood-brain barrier, downregulating the immune system and lowering neuroinflammation. By reducing the production of pro-inflammatory cytokines and increasing the levels of anti-inflammatory cytokines, CBD is hypothesized to improve long COVID symptoms.3 In addition, CBD improves symptoms common in many long COVID patients, such as anxiety, insomnia, cognitive impairment, and neuropathic pain.
What evidence supports the use of cannabidiol for long COVID?
Cannabidiol has been previously studied as a potential treatment for COVID symptoms in mild to moderate-severity infections. In a randomized placebo-controlled study of 105 patients, participants were randomized to receive 300 mg of CBD or placebo added to standard care for 14 days.4 The study found no differences between CBD and placebo in reducing or preventing worsening of clinical status for a COVID infection. Thus, CBD should not be used in the treatment or prevention of an active COVID infection.
There is currently a lack of studies investigating the use of cannabidiol for long COVID. A randomized controlled trial of 24 participants studied the use of a cannabidiol formulation in post-acute COVID-19 syndrome and found subjectively reported improvement in overall symptoms.5 A study conducted in the UK is currently under peer review in which 30 participants were prescribed CBD-dominant medical cannabis daily for five months. Breathlessness, fatigue, mood, cognition, and pain were assessed to determine the safety and efficacy of CBD for long COVID.6
What are some things to watch out for with cannabidiol?
No serious adverse events have been reported from trials. CBD is often well-tolerated but can cause side effects such as dry mouth, nausea, diarrhea, fever, drowsiness, fatigue, and changes in appetite.4,7 It is important to remember that the FDA does not approve nonprescription CBD products, and the quality and purity of these products may vary. CBD can also have drug interactions with many medications, including blood thinners (such as warfarin), anti-epileptic drugs, antidepressants, opioids, statins, and more. It is important to tell your doctor or pharmacist if you are taking CBD regularly to see if there are any potential drug interactions with your other medications.
References:
2) Reyer M. Researchers recommend clinical trials for CBD to prevent COVID-19 based on promising animal data. UChicagoMedicine. January 20, 2022. Accessed November 10, 2023. https://www.uchicagomedicine.org/forefront/research-and-discoveries-articles/researchers-recommend-clinical-trials-for-cbd
6) Thurgur H, Lynskey M, Schlag A, et al. Feasibility of a cannabidiol (CBD)-dominant cannabis based medicinal product (CBMP) for the treatment of Long COVID symptoms: A single arm open label feasibility trial. Authorea. July 4, 2023. Accessed November 10, 2023. https://www.authorea.com/users/635694/articles/652949-feasibility-of-a-cannabidiol-cbd-dominant-cannabis-based-medicinal-product-cbmp-for-the-treatment-of-long-covid-symptoms-a-single-arm-open-label-feasibility-trial
7) Bauer BA. What are the benefits of CBD – and is it safe to use? Health Lifestyle Consumer Health. Mayo Clinic. December 6, 2022. Accessed November 10, 2023. https://www.mayoclinic.org/healthy-lifestyle/consumer-health/expert-answers/is-cbd-safe-and-effective/faq-20446700#:~:text=Though%20it%27s%20often%20well%2Dtolerated,dosage%20of%20CBD%20in%20products
Active Clinical Trials: Long COVID, cannabidiol | Card Results | ClinicalTrials.gov
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