Nasal Saline Irrigation for long COVID
NASAL SALINE IRRIGATION
What is nasal saline irrigation?
Nasal saline irrigation, often done with a neti pot, is a non-medicated alternative that can be used as an additional treatment to relieve nasal congestion from allergies or upper respiratory tract infections. To perform nasal saline irrigation, wash and completely dry the neti pot or a similar device before use. Prepare the saline rinse with preferably distilled or sterile water. Lean over a sink and tilt your head sideways and downward to keep the saline rinse from flowing into your mouth. Breathe through your mouth while inserting the neti pot into your upper nostril so the saline can drain from the other nostril. Then repeat on the other side.
How can nasal saline help alleviate certain long COVID symptoms?
The primary target of the SARS-CoV-2 virus starts initially in the nasal epithelium and spreads to the throat and airways. It is believed that nasal saline irrigation can help to remove and limit the viral load in the nasal passages and throat. When added to standard-of-care measures, nasal saline irrigation has been shown to clear viral loads faster in more severe or hospitalized COVID patients.1 In vitro, saline has also been reported to reduce viral replication by 50-98%.1 Also, earlier studies have shown that nasal saline may even help reduce household transmission of COVID.2 Given its ability to clear the nasal passages, nasal saline may help in the reduction of nasal symptoms post-COVID as well as smell or taste dysfunction.
What evidence supports the use of nasal saline for long COVID?
In a study of 140 patients with 68 participants who performed daily nasal saline irrigations for 12 days, there was an average reduction of 24.7% in nasal congestion, a runny nose, and sneezing.3 Smell or taste dysfunction may take 10-40 days to resolve with nasal saline irrigation, and the evidence is somewhat mixed in effectiveness.1 In the previously mentioned study, lack of smell and taste did not vary significantly between the treatment and control groups.3 However, other studies have found significant differences in loss of smell between patients who used nasal saline irrigation and gargling and those who did not.4 Another study found that using nasal saline irrigation in combination with triamcinolone acetonide nasal spray (a topical corticosteroid available over the counter) significantly improved the sense of smell compared to nasal saline irrigation alone.5
What should you be aware of when using nasal saline?
Nasal saline irrigation appears to be safe with no reported serious adverse events with proper administration. Remember to thoroughly wash your neti pot before and after each use. Some may experience nasal irritation and stinging. Reducing the amount of salt in the solution or adjusting the temperature of the water may help. It is important to use distilled or sterile water to prevent potential infection from tap water.
References:
L-Carnitine for long COVID
L-CARNITINE
What is Carnitine?
Carnitine is a generic term for several highly related compounds, such as L-carnitine, acetyl-L-carnitine, and propionyl-L-carnitine. As a nutrient, carnitine is comprised of two essential amino acids, lysine and methionine [[1]]. We get carnitine from foods, especially animal products, and we can also get it from supplements [[2]]. Carnitine deficiency creates fatigue, tiredness, and lethargy [[1]].
Within the cell, L-carnitine and acetyl-l-carnitine are virtually identical, as one can be converted to the other easily. Acetyl-carnitine has better gut absorption than carnitine and can cross the blood-brain barrier, which gives it some advantages from a drug delivery standpoint [[3]].
What does carnitine do in the body?
L-carnitine and a similar compound, acetyl-l-carnitine, both work to improve mitochondrial function [[4]]. Mitochondria are the cell’s powerhouse, generating chemical energy to fuel the cell’s processes. Mitochondrial damage is linked to early aging and neurodegeneration. Carnitine and acetyl-l-carnitine have an important mitochondrial function [[5]].
How can carnitine help alleviate certain Long COVID symptoms and pathophysiology?
Fatigue is a feature of Long COVID, and previous studies of carnitine have shown that it can reduce fatigue in people with chronic diseases such as cancer and multiple sclerosis [[1]]. This leads researchers to believe carnitine can also help relieve fatigue in Long COVID [[6]].
Carnitine’s antioxidant properties are also relevant to Long COVID. Supplementing carnitine, CoQ10, and lipoic acid can lower inflammatory markers, which can be elevated in Long COVID. Lastly, carnitine can boost anti-inflammatory and antioxidant mechanisms along with its anti-fatigue characteristics. Potentially, carnitine can also regulate the formation of acetylcholine, a substance in the brain that is involved in memory [[1]].
Rhexical Plus Tablet
- Rhexical Plus Tablet replenishes nutritional deficiency.
- Elemental Calcium is used to prevent or cure low blood calcium levels in patients who do not ingest enough calcium.
- Vitamin D3 (Cholecalciferol) regulates calcium and phosphate levels in the body.
- L-5-Methyltetrahydrofolate aids in the treatment or prevention of low folate levels.
- Methylcobalamin helps to enhance the nervous system and is essential for DNA synthesis and maturation.
- Pyridoxine-5-Phosphate is responsible for various functions such as energy production and amino acid metabolism.
- Vitamin K2-7 is essential for calcium metabolism (the main mineral found in the bones and teeth).
Neurofeedback for long COVID
NEUROFEEDBACK
What is neurofeedback?
Neurofeedback is a brain training process that allows people to self-control their brain functions by measuring their brain waves and then providing a feedback signal to encourage or discourage a certain brain activity.1 This is done by placing electrodes on a particular part of the patient’s head to obtain their electroencephalographic (EEG) or brain wave activity. When the detected EEG activity is in an optimal range, the patient receives a visual or auditory cue that is perceived as “good” and is considered a reward. When the EEG activity is abnormal, the patient receives feedback that it is “bad” to encourage the patient to change their brain activity.
Consistent sessions are needed to reinforce positive changes in brain function. Typically, patients will notice a difference of about ten sessions; however, 20 sessions are generally required to retrain the brain.
How can neurofeedback help alleviate certain long COVID symptoms?
Neurological symptoms of long COVID can include headache, insomnia, anxiety, depression, dizziness, seizures, and fatigue.2 There are several proposed mechanisms for why COVID can cause these symptoms. Damage to neural tissue can be caused by direct and indirect interaction of the SARS-CoV-2 virus with the brain. The SARS-CoV-2 virus is believed to reach the brain through the blood and infect neurons and astrocytes, which make up a large portion of the central nervous system. COVID can also indirectly impact the brain with respiratory symptoms that prevent sufficient oxygen from reaching the brain and a heightened pro-inflammatory response that can damage neural tissue.2
Various studies have also noted EEG abnormalities in COVID patients.3 Retraining the brain to allow a patient to correct these EEG abnormalities is believed to be able to make micro-structural changes of white and gray matter in the brain and improve plasticity with improvement in the trained brain areas.2 Neurofeedback has been studied for headaches, insomnia, depression, and fatigue and has been used in multiple sclerosis patients who can experience symptoms similar to those of neurological long COVID symptoms.
What evidence supports the use of neurofeedback for long COVID?
A pilot study looking at the use of neurofeedback therapy on post-COVID fatigue, anxiety, and depression included 10 participants experiencing these symptoms for at least three months. Electrodes were placed on the right and temporal lobes, and the participants underwent five sessions, each 25-45 minutes, completed within two weeks. The study found a significant reduction in anxiety and depression persisting for at least one month but an insignificant effect on fatigue.4
A review of 12 studies assessing the effect of EEG-based neurofeedback on depression found significant cognitive, clinical, and neural improvements in patients’ depressive symptoms.5 Thus, it appears that neurofeedback therapy can be an effective non-pharmacologic treatment method for new-onset anxiety and depression in post-COVID individuals; however, more studies are needed to assess its efficacy in long COVID.
What should you be aware of with neurofeedback?
Neurofeedback therapy has a relatively low risk of side effects, but side effects can include anxiety, agitation, emotional lability, headaches, and fatigue.6 These side effects are often transient. Severe side effects are rare but include seizures, depression, manic attacks, and memory problems.
References:
Vitamin E for long COVID
VITAMIN E
What is vitamin E?
Vitamin E is an antioxidant known for its free radical scavenging properties [[1]]. It is a fat-soluble vitamin [[2]]. We get vitamin E entirely from dietary sources [[3]].
What does vitamin E do in the body?
Vitamin E is potent against cancer, aging, arthritis, and cataracts. It is also vital for the health of our visual and reproductive systems. It also prevents platelet aggregation and can combat atherosclerosis [[3]].
Vitamin E is an antioxidant, which means that it protects the body’s cells from free radicals. Free radicals are a form of oxidative stress that causes cell and tissue damage. Vitamin E also supports immune health, enabling the body to fight off viruses. Its functions include widening blood vessels, preventing blood clots, and improving communication between cells [[2]].
How can vitamin E help alleviate certain Long COVID symptoms and pathophysiology?
Because of its role as a scavenger of harmful free radicals, vitamin E can protect against oxidative damage caused by COVID-19, both in the acute and post-acute phases. Research suggests that vitamin E may have anticlotting effects, which can be useful for acute COVID-19, given that blood thickening is a common symptom associated with severe COVID-19 and is also a feature of Long COVID [[4]].
Vitamin E may also have anti-platelet and anti-clotting effects, which can promote vasculature health. Given that clotting abnormalities can be a feature in severe COVID-19 and Long COVID, vitamin E can potentially reduce blood clot risks for both patient populations [[4]].
Vitamin E may lower levels of an inflammatory substance known as C-reactive protein or CRP [[5]], which can be elevated in patients with Long COVID [[6]].
Dimenhydrinate for long COVID
DIMENHYDRINATE
What is dimenhydrinate?
Dimenhydrinate is a first-generation antihistamine commonly used for motion sickness, nausea, vomiting, and vertigo (a sensation that you or your surroundings are spinning). It is similar to meclizine (another over-the-counter antihistamine used for motion sickness and vertigo), but dimenhydrinate is considered to be more sedating. Compared to meclizine, which takes an hour to take effect but lasts 24 hours, dimenhydrinate has a faster onset of action of about 15 to 30 minutes but takes about an hour. Dimenhydrinate can be taken as 50-100 mg every four to six hours as needed for a maximum of 400 mg daily.
How can dimenhydrinate help alleviate certain long COVID symptoms?
Some patients have reported neurological symptoms of long COVID, such as vertigo and persistent dizziness. While rare, there have been reports of new-onset vertigo associated with a COVID infection.1 It is known that the SARS-CoV-2 virus can infiltrate the central nervous system and directly invade the brain. The mechanism of its association with vertigo is still unclear. Still, it is thought to be due to the effect of the virus on neural networks impacting our hearing and balance or cytokine storm that occurs when immune cells become hyperactivated and trigger an excess release of inflammatory mediators.2 Dizziness can also be due to multiple factors such as dehydration, headache, and lightheadedness due to stress from the infection.
Dimenhydrinate can block certain receptors in the chemoreceptor trigger zone in our brain, which is responsible for causing feelings of nausea and dizziness. This allows for relief of vertigo and dizziness from neurological long COVID symptoms.
What evidence supports dimenhydrinate’s use for long COVID?
More studies are currently needed to explore the use of dimenhydrinate specifically for new-onset vertigo or dizziness after a COVID infection. In addition, patient case reports and anecdotal reports are mixed, with some reporting beneficial effects and others stating partial or no improvement in their vertigo. A case report of a patient treated with dimenhydrinate and beta-histamine (a prescription antiemetic not available in the US) led to partial improvement in vertigo.3 For patients with gastrointestinal effects from COVID, such as nausea and diarrhea, dimenhydrinate can help with oral intake and rehydration.4
Overall, dimenhydrinate is a reasonable option to consider for post-COVID vertigo or dizziness and can be trialed with other prescription medications. However, it should not be used chronically if these symptoms persist.
What should you be aware of when taking dimenhydrinate?
Due to its sedating effects, dimenhydrinate should not be taken while driving or operating heavy machinery. Other side effects of the medication include a fast heartbeat or palpitations, dizziness, headache, restlessness, blurred vision, difficulty urinating, or constipation. Some of these side effects can be worsened with other medications and older age. If used more frequently, it should be used with caution in patients with cardiovascular disease, angle-closure glaucoma, and urinary obstruction.
References:
Olfactory Training for longCOVID
OLFACTORY TRAINING
What is olfactory training?
Olfactory training is a non-pharmacological and non-surgical treatment option for people experiencing olfactory (or smell) dysfunction that can occur after an infection, trauma event, or Parkinson’s disease. Typically, patients expose themselves to 4 different odors twice daily for at least 24 weeks. Each odor is sniffed for at least 20-30 seconds without a break. Each odor should ideally represent a different category of smells, including a fruity or sweet smell (ex, lemon), flowery smell (ex, rose), spicy smell (ex, clove), and resinous smell (ex, eucalyptus).2 Olfactory training can also be done for up to 12 odors, which may demonstrate better symptom improvement.1 It is more effective in younger individuals and those with more severe olfactory dysfunction.
How can olfactory training help alleviate certain long COVID symptoms?
It is estimated that up to one-third of COVID patients can have post-infection smell dysfunction.3 The loss of smell is likely due to multiple mechanisms such as inflammation of the nasal epithelium, damage of olfactory neurons and microglial cells, early cell death of olfactory cells, changes in the nasal cilia, and changes in odor transmission. Olfactory training is believed to help rebuild neural connections between the nose and the brain to help relearn and identify different types of smells.2
What evidence supports olfactory training’s use for long COVID?
A case series of 8 patients (five female, three male) with post-COVID smell dysfunction lasting over three months followed a 30-day olfactory training protocol using plant-derived essential oils. Participants had one training session in the morning and one in the evening, each lasting approximately 15 minutes. Each patient was asked to smell ten plant-derived essential oils through deep inhalation and rapid sniffing. The order of smells included peppermint, lavender, lemon, red spruce, frankincense (orange-like smell), Hyssop CT pinocamphone (spice and herbaceous scent), cinnamon, cloves, savory, and eucalyptus. Based on their self-reported olfactory functioning, there was a significant improvement from 3.6 at baseline to 5.6 out of 10.3
Olfactory training is typically done over a longer time span of 12-24 weeks. However, additional studies have looked at using an expanded number of smells for a shorter time span. One study enrolled 80 patients assigned to olfactory training with four or eight smells over four weeks.4 Significant improvements were subjectively measured in both groups, and there were no significant differences between groups in identifying smells. This suggests that utilizing four scents for four weeks may be sufficient for olfactory training.
Another study investigated the efficacy of combined visual-olfactory training compared to olfactory training alone in 275 patients with post-COVID olfactory loss.5 Visual-olfactory training included digital images of each scent shown to the participants while smelling it. The study also examined differences between patients choosing scents vs. physicians selecting scents. Results showed no clinically meaningful difference in all groups’ smell identification test scores.
What should you be aware of with olfactory training?
Olfactory training is safe and considered a first-line therapy for olfactory dysfunction. However, certain conditions may benefit from surgery rather than olfactory training, so it is important to ask your doctor before starting it. Smoking tobacco products can worsen olfactory functioning and prevent improvement with olfactory training.
References:
2) Windsor M. Smell training is brain training, parosmia success – and five other insights from a new UAB clinic. The University of Alabama at Birmingham. March 27, 2023. Accessed November 2, 2023. https://www.uab.edu/reporter/patient-care/advances/item/10005-smell-training-is-brain-training-parosmia-success-and-five-other-insights-from-a-new-uab-clinic#:~:text=Treatments%20—%20starting%20with%20olfactory%20training,training%20can%20boost%20cognitio
Specialized Pro-Resolving Mediators for long COVID
SPECIALIZED PRO-RESOLVING MEDIATORS (SPM)
What are specialized pro-resolving mediators?
Specialized pro-resolving mediators, or SPMs, are fatty substances produced within the body that work to reduce inflammation.
What do specialized pro-resolving mediators do in the body?
SPMs have many functions, including ending chronic inflammatory processes, reducing pain, affecting innate and adaptive immune cells, clearing dead cells and debris, breaking down blood clots, and attacking pathogens. SPMs can also help support tissue regeneration [[1]].
SPMs are bioactive lipids (fats) that occur via the breakdown of certain polyunsaturated fatty acids after the inflammatory cascade has started. They may aid in the inflammatory process that helps resolve the inflammation. This is why SPMs could help improve the overall course of heart and lung tissue inflammation events. SPMs also have many other immune functions, such as regulating macrophages, cytokine production, and stimulation of macrophages that resolve inflammatory courses [[2]].
The list of SPM compounds includes lipids (fats) such as lipoxins, resolvins, protectins, and maresins [[2]]. Lipoxins are anti-inflammatory, pro-inflammation resolution molecules that can reduce chronic inflammation and tissue injury [[3]]. Resolvins and protectins are derived from omega-3 fatty acids and work to resolve inflammation [[4]]. Maresins are analgesic and anti-inflammatory macrophages that mediate the resolution of inflammation [[5]].
How can specialized pro-resolving mediators help alleviate certain Long COVID symptoms and pathophysiology?
Prolonged inflammation after COVID-19’s acute phase is over can damage tissues in the brain, lungs, and kidney [[6]]. SPM’s role in resolving pro-inflammatory processes can help Long COVID survivors with the resolution phase of inflammation, improving the overall course of chronic inflammation.
Guanfacine for long COVID
GUANFACINE
What is guanfacine?
Guanfacine is a medication commonly used for blood pressure and attention-deficit/hyperactivity disorder (ADHD). Immediate-release (IR) tablets are used for blood pressure, whereas extended-release (ER) tablets are used for ADHD, often in combination with other medications. Guanfacine is a centrally acting alpha2A-adrenergic receptor agonist. Guanfacine treats high blood pressure by decreasing heart rate and relaxing the blood vessels so blood can flow more easily. Guanfacine ER tablets may treat ADHD by affecting the part of the brain that controls attention and impulsivity, the prefrontal cortex [1]. Guanfacine is not a stimulant, unlike most medications prescribed for ADHD; therefore, it lacks addictive qualities. Coupled with its relatively affordable nature, it could be a very appealing option to many patients.
How does guanfacine relate to 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. Through its supposed effects on the prefrontal cortex, guanfacine could be helpful in those suffering from “brain fog.”
Although a lengthy clinical trial has yet to be completed, one researcher from Yale found evidence of guanfacine decreasing “brain fog” in long COVID patients. [2]. He completed a small study with 12 patients all experiencing “brain fog” post-COVID. Patients were given guanfacine and N-acetylcysteine (NAC), an antioxidant with anti-inflammatory properties. Of those 12 patients, eight experienced relief from “brain fog.” Two patients were lost to follow-up, and two stopped the treatment due to side effects [2]. Guanfacine is an attractive medication option to help with memory and concentration problems for those suffering from long-COVID. Although no formal recommendations have been made regarding its use, it shows promise to patients.
References:
1https://medlineplus.gov/druginfo/meds/a601059.html
Mirtazapine for long COVID
MIRTAZAPINE
What is mirtazapine (Remeron)?
Used for depression, mirtazapine is a medication belonging to the tetracyclic antidepressant drug class. Mirtazapine is different than other antidepressants in that it works on alpha-2 adrenergic receptors. Inhibition of these receptors results in an increased availability of both serotonin and norepinephrine. Serotonin is a molecule in the body that aids in mood, sexual desire, sleep, digestion, wound healing, bone health, and blood clotting [1]. It is often referred to in psychology as the “happy” chemical. Norepinephrine is thought to play a role in the body’s stress response and helps to regulate sleep, alertness, and blood pressure [2].
How can mirtazapine be used in long-COVID?
Mirtazapine may also benefit the long-COVID patient population. Many of those diagnosed with long-COVID suffer from “brain fog,” memory problems, difficulty concentrating, and forgetfulness. The proposed reason is that during a COVID-19 infection, the body’s immune response becomes activated, causing heavy amounts of inflammation, including in the central nervous system (CNS) [3]. Those with long-COVID live in a state of inflammation, manifesting as the symptoms associated with “brain fog.”
In addition to aiding in several bodily processes, serotonin also protects against viral inflammation by blocking certain viruses (like HIV-1) from entering the cells. It can also decrease cytokine production, promoting the immune response [3]. Currently, its use is limited to depression. There is no evidence to support the use of mirtazapine in treating COVID-19 itself. However, it may be beneficial if more studies are conducted to examine its effects.
References:
1 https://my.clevelandclinic.org/health/articles/22572-serotonin
2https://americanaddictioncenters.org/antidepressants-guide/ndris
![](https://compendirx.com/wp-content/themes/medical-directory-child/assets/img/insta.png")
