Maraviroc for long COVID
MARAVIROC
What is maraviroc (Selzentry)?
Maraviroc is a medication used to treat human immunodeficiency virus (HIV) in both children and adults. It works by binding to a receptor on HIV, prohibiting it from entering the cells [1]. Maraviroc is not a stand-alone treatment and must be used in combination with other HIV medications.
How does the use of maraviroc relate to long-COVID?
For patients with long-COVID, treatment options are limited and undefined. Researchers have turned to existing medication therapies in hopes they prove useful. Maraviroc is one option that may be beneficial. In long-COVID, it is theorized that a person is not actively infected but is still shedding the virus in the body. By using maraviroc, the virus will be inhibited from entering the cells, leading to viral death and remission for the patient.
Few studies have determined whether Maraviroc shows benefits. The few that have been completed did show some promise. One study looked at 18 patients prescribed maraviroc and pravastatin, a medication used to lower cholesterol. These patients displayed clinical improvement in symptoms after 12 weeks of treatment. Unfortunately, before this study, these patients used other potential long-COVID treatments, thus confounding whether these results were due to maraviroc, pravastatin, or other therapies [2].
Maraviroc may be a potential option to treat long-term COVID; however, further research needs to be completed to examine its effects on the virus itself. At this time, two additional clinical studies aiming to examine the use of maraviroc in COVID-19 patients have been completed; however, results from these studies are not yet available [3].
References:
1http://www.antimicrobe.org/drugpopup/Maraviroc.htm
2https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9944830/
3https://clinicaltrials.gov/study/NCT04435522?term=COVID&cond=Maraviroc&city=&rank=1
Active Clinical Trials: Long COVID, maraviroc | Card Results | ClinicalTrials.gov
Propranolol for long COVID
PROPRANOLOL
What is propranolol?
Propranolol, a medication in the class called beta blockers, is used to treat heart conditions in patients. Beta-blockers work by acting on the beta receptors in the heart, blocking its action and resulting in a decrease in blood pressure.
How can propranolol be used for those with long-COVID?
Recent research has shown that this class of medications may be helpful for those suffering with symptoms of long-COVID. Patients diagnosed with long-COVID often experience symptoms such as lightheadedness, postural orthostatic tachycardia syndrome (POTS), chest pain, and a fast heartbeat. Cardiologists at Cedars-Sinai Hospital have found that treatment with beta-blockers, combined with a low salt intake and adequate hydration, can improve long-COVID symptoms [1].
There is also evidence to suggest that beta blockers have some anti-inflammatory effects. In addition to increasing the heartbeat, beta receptors are pro-inflammatory. They release certain signals that aid in activating the immune response. By blocking these signals, the immune system response decreases, leading to a decrease in clinical symptoms in patients [2]. Additional research is needed to fully understand the scope of propranolol and long-COVID; however, the positive evidence recently discovered provides hope that it may be useful for patients.
References:
2https://www.frontiersin.org/articles/10.3389/fimmu.2021.749291/full
IV Hydration for long COVID
IV HYDRATION/VITAMIN THERAPY
What are IV hydration and vitamin therapy?
Many products on the market are labeled IV hydration or vitamin therapy for long COVID and contain various combinations of intravenous vitamins, antioxidants, and amino acids such as vitamin C, vitamin B12, vitamin D, and glutathione. For hydration, they can also contain added electrolytes and fluids. IV infusions are directly absorbed into the bloodstream, whereas oral supplements must be absorbed from the gastrointestinal system before they can reach the bloodstream. Thus, IV infusions can be more effective in supplementation than oral vitamins.
How can IV hydration/vitamin therapy help alleviate certain long COVID symptoms?
An excess release of inflammatory mediators and oxidative stress are believed to be contributing factors in long COVID that lead to a hyperinflammatory state. This oxidative stress and inflammation can lead to the progression of fatigue and neuropsychiatric symptoms, as well as disruptions in blood flow.1 Vitamins such as vitamin C have antioxidant and anti-inflammatory properties that are believed to relieve some of these symptoms. During acute infections, the demand for vitamin C may be high due to an elevated inflammatory response and high metabolic demand; thus, COVID patients can show severe deficiencies in vitamin C. As a result, IV vitamin therapies may help with these deficiencies and reduce inflammation in the body.
What evidence supports the use of IV hydration/vitamin therapy for long COVID?
The use of IV hydration/vitamin therapy for long COVID is controversial. For commercial IV products and IV vitamin clinics marketed online, there have been no studies to demonstrate their effectiveness other than anecdotal patient stories.
The primary intravenous vitamin studied in clinical trials for fatigue is vitamin C. In a systematic review of 9 studies with 720 participants, 3 out of 4 controlled trials showed significantly decreased fatigue after IV vitamin C therapy. All except one of the observational studies also noted a decrease in fatigue scores. Other symptoms that were alleviated include sleep disturbances, difficulty concentrating, depression, and pain. However, these studies mainly focused on fatigue in cancer patients rather than long COVID patients.2
High-dose IV vitamin C has been studied for use in an acute COVID infection with mixed results. One clinical trial of 60 patients randomized to high-dose IV vitamin C or standard COVID antiviral therapy did not find significantly better outcomes in the group treated with IV vitamin C regarding the amount of oxygen saturation at discharge, length of ICU stay, or mortality.3 Another trial of 54 patients with COVID pneumonia randomized to IV vitamin C 2 grams every 6 hours for five days vs. standard treatment found a significant increase in oxygen saturation and a decrease in respiratory rate.4
Overall, there are proposed associations between IV vitamin therapy (specifically vitamin C) and improvement in fatigue. Still, more evidence from clinical trials needs to support its use in long-term COVID patients. In addition, patients with sufficient vitamin levels in their diet should not require additional supplementation.
What should you be aware of when using IV hydration/vitamin therapy?
Given that some IV hydration/vitamin therapies are offered in various settings, such as spas and salons that may not have medical providers administering the infusion, it is important to consult your doctor before considering one. Patients with congestive heart failure or end-stage renal disease must use caution when receiving IV fluids, as it can exacerbate their conditions. These IV therapies are also not regulated by the FDA. They could carry a risk of infection, damage to the injection site, irritation or inflammation of a vein, or air embolism from air entering the IV.5 In addition, these IV therapies can be fairly expensive.
References:
5) Talk with your provider before undergoing IV vitamin therapy. UCLA Health. November 19, 2018. Accessed November 5, 2023. https://www.uclahealth.org/news/talk-with-your-provider-before-undergoing-iv-vitamin-therapy
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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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