Fluticasone Nasal Spray for long COVID
FLUTICASONE NASAL SPRAY
What is fluticasone?
Fluticasone is a nasal corticosteroid used for symptoms of seasonal allergies such as sneezing, nasal congestion, a runny nose, and inflamed sinuses. There are two formulations of fluticasone that you can find over the counter: fluticasone propionate (Flonase Allergy Relief) and fluticasone furoate (Flonase Sensimist). Fluticasone propionate can be used twice daily, while fluticasone furoate should be used once daily because of its longer duration of action. The recommended maximum dose can be given as two sprays in each nostril once daily. Fluticasone furoate may be preferred for some because of its aftertaste compared to fluticasone propionate.1
How can fluticasone help alleviate certain long COVID symptoms?
The SARS-CoV-2 virus is known to enter ACE2 receptors in the nasal mucosa, which activates an inflammatory response that can lead to olfactory dysfunction. An estimated 19-68% of COVID patients may present with olfactory dysfunction that can linger after the infection has passed.2 Nasal corticosteroids like fluticasone may help improve loss of smell and taste from COVID. The mechanism behind this is not fully known, but it may be due to reduced inflammatory swelling of the nasal passage to allow for the increased penetration of odors.3
What evidence supports fluticasone’s use for long COVID?
Several reports have recommended an intranasal corticosteroid such as fluticasone for patients with post-COVID olfactory dysfunction symptoms lasting longer than two weeks.2 In a study done with 120 patients that looked at the use of fluticasone propionate nasal spray with a triamcinolone paste for loss of smell, they found significant improvement in the ability to smell five tested odors and taste four different flavors within a week of use.4 However, there are some concerns with the study methods used in the trial, such as an unstandardized test of assessing odors and tastes and using the nasal spray at the onset of olfactory symptoms rather than after two weeks of symptoms.5
A systematic review of 21 studies found that an intranasal corticosteroid such as triamcinolone or fluticasone helped COVID patients regain their sense of smell 23 days earlier than with an oral corticosteroid or another intranasal corticosteroid called mometasone furoate.6 It is also recommended that this be done with olfactory or smell training, which exposes patients to four different odors twice a day for at least 24 weeks.
What should you be aware of when taking fluticasone?
Some side effects of fluticasone include headache, nose bleeds, and throat irritation. When using fluticasone, consider applying it contralaterally by spraying your right hand in your left nostril and vice versa. This directs the medication away from your nasal septum to prevent nasal septal perforations or ulcerations. This product should be avoided after recent nose ulcers, nasal trauma, or nose surgery until the nostril is healed. Because fluticasone is a steroid nasal spray, it should not be used chronically. It should also be used with caution in people with cataracts and glaucoma.
For children 11 years old or younger, fluticasone should not be used more than one spray per nostril daily, as it may suppress their growth if used chronically. Flonase Allergy Relief (fluticasone propionate) should not be used in children under four, and Flonase Sensimist (fluticasone furoate) should not be used in children under two.
References:
Triamcinolone Acetonide Nasal Spray (Nasacort) for long COVID
TRIAMCINOLONE ACETONIDE NASAL SPRAY
What is triamcinolone?
Triamcinolone is available as an over-the-counter nasal corticosteroid spray (Nasacort) used to relieve symptoms of seasonal and year-long allergies such as sneezing, nasal congestion, and a runny nose. It can be applied as two sprays (or 110 mcg) in each nostril once daily and then one spray once daily in each nostril once symptoms are more controlled. Triamcinolone should not be used if there is no relief after three weeks.
How can triamcinolone nasal spray help alleviate certain long COVID symptoms?
The SARS-CoV-2 virus is known to enter ACE2 receptors in the nasal mucosa, activating an inflammatory response that can lead to olfactory dysfunction. An estimated 19-68% of COVID patients may present with olfactory dysfunction that can linger after the infection has passed.1 Nasal corticosteroids like triamcinolone may be used to improve loss of smell post-COVID. The mechanism behind this is not fully known, but it may be due to reduced inflammatory swelling of the nasal passage that allows for the increased penetration of odors.2
What evidence supports the use of triamcinolone nasal spray for long COVID?
Several reports have recommended an intranasal corticosteroid such as fluticasone for patients with post-COVID olfactory dysfunction symptoms lasting longer than two weeks.1 In a study of 120 patients that looked at the use of fluticasone propionate nasal spray with a triamcinolone paste for loss of smell, there was significant improvement in the ability to smell five tested odors and taste four different flavors within a week of use.3 However, the effects of triamcinolone paste may not be the same as those of a triamcinolone nasal spray due to differences in how the drug is absorbed through different routes of administration.
A systematic review of 21 studies found that the use of an intranasal corticosteroid such as triamcinolone or fluticasone was able to help COVID patients regain their sense of smell 23 days earlier than with an oral corticosteroid or another intranasal corticosteroid called mometasone furoate.4 It is also recommended to be combined with olfactory or smell training, which exposes patients to four different odors twice a day for at least 24 weeks.
What should you be aware of when using triamcinolone nasal spray?
Triamcinolone can have some local effects, such as a burning or stinging sensation in the nose. It can also cause nosebleeds and may have a bitter aftertaste for some people. If you are experiencing mucous crusting around your nostrils, you can consider rinsing with a nasal saline spray before applying triamcinolone.
When using triamcinolone, consider applying it contralaterally by spraying it in your left nostril with your right hand and vice versa. This directs the medication away from your nasal septum to prevent nasal septal perforations or ulcerations. This product should be avoided after recent nose ulcers, nasal trauma, or nose surgery until the nostril is healed. Because triamcinolone is a steroid nasal spray, it should not be used chronically. It should also be used with caution in people with cataracts and/or glaucoma.
References:
Tollovid for long COVID
TOLLOVID
What is Tollovid?
Tollovid is a blend of plant extracts. It is in clinical studies to treat both COVID-19 and Long COVID. Having shown promising data in acute COVID-19, studies are underway to assess its use for Long COVID [[1]].
What does Tollovid do in the body?
Tollovid works by inhibiting the activity of an enzyme known as the 3CL protease. This enzyme is involved in the replication of coronaviruses inside our cells. Once the virus synthesizes its RNA into a long polyprotein, the protease breaks down the proteins, helping form the coronavirus molecules [[2]]. By inhibiting the 3CL protease, Tollovid stops coronaviruses’ ability to replicate. Tollovid may also have anti-cytokine properties [[3]].
How can Tollovid help alleviate certain Long COVID symptoms?
Evidence suggests that, in some patients with Long COVID, the SARS-CoV-2 virus that causes COVID-19 persists in their bodies even after their bout with COVID-19. Therefore, Tollovid may help neutralize the effects of the lingering virus in these patients. The virus may persist, especially in the gut, leading to persistent inflammatory responses. In a non-peer-reviewed study conducted by the manufacturers of Tollovid, the supplement decreased symptoms, including fatigue and congestion, in both acute COVID and Long COVID. 46.2% of Long COVID patients reported reduced symptoms in the study [[4]]. The company also recently published a non-peer-reviewed case study in which one Long COVID patient with microclots benefitted after taking Tollovid [[5]].
[1] https://www.biospace.com/article/releases/todos-medical-announces-positive-biomarker-data-from-phase-2-trial-of-tollovir-in-hospitalized-covid-19-patients/
[3] https://www.researchgate.net/profile/Andrew-Blumenthal/publication/362791461_VALUE_OF_3CL_PROTEASE_INHIBITOR_SUPPLEMENTATION_1_The_Value_of_3CL_Protease_Inhibitor_Supplementation_in_Long_Haul_Syndrome_Patients_The_Value_of_3CL_Protease_Inhibitor_Supplementation_in_Long_Haul_Sy/links/62ff607daa4b1206fabfa146/VALUE-OF-3CL-PROTEASE-INHIBITOR-SUPPLEMENTATION-1-The-Value-of-3CL-Protease-Inhibitor-Supplementation-in-Long-Haul-Syndrome-Patients-The-Value-of-3CL-Protease-Inhibitor-Supplementation-in-Long-Haul-Sy.pdf
[4] https://www.researchgate.net/profile/Andrew-Blumenthal/publication/362791461_VALUE_OF_3CL_PROTEASE_INHIBITOR_SUPPLEMENTATION_1_The_Value_of_3CL_Protease_Inhibitor_Supplementation_in_Long_Haul_Syndrome_Patients_The_Value_of_3CL_Protease_Inhibitor_Supplementation_in_Long_Haul_Sy/links/62ff607daa4b1206fabfa146/VALUE-OF-3CL-PROTEASE-INHIBITOR-SUPPLEMENTATION-1-The-Value-of-3CL-Protease-Inhibitor-Supplementation-in-Long-Haul-Syndrome-Patients-The-Value-of-3CL-Protease-Inhibitor-Supplementation-in-Long-Haul-Sy.pdf
Heart Rate Variability (HRV) Biofeedback for long COVID
HEART RATE VARIABILITY (HRV) BIOFEEDBACK
What is HRV biofeedback?
Heart Rate Variability (HRV) biofeedback is a non-invasive method of matching your breathing to heart rate patterns. Your heart rate speeds up as you inhale and slows down as you exhale. During HRV biofeedback, patients can visually see their beat-by-beat heart rate data and try to slow down their breathing to match their heart rate patterns.1 The patient receives immediate feedback from the device throughout this process. Patients are trained to breathe from their diaphragm to reduce their respiration rate to about six breaths per minute. Slowing down the heart rate activates the parasympathetic nervous system, which conserves our energy and allows our body to rest and relax.
HRV biofeedback has been used for asthma, depression, anxiety, stress, and muscle relaxation. For individuals looking for non-pharmacological ways of alleviating these symptoms, HRV biofeedback is a reasonable therapy to try first before other methods, such as neurofeedback.
How can HRV biofeedback help alleviate certain long COVID symptoms?
The SARS-CoV-2 virus can lead to heart damage through multiple mechanisms. The binding of the virus to ACE2 receptors can have negative downstream impacts on the cardiovascular system. Direct myocardial damage from vascular inflammation and indirect damage from lack of oxygen, stress-induced heart abnormalities, and increased risk of clotting can all result in cardiovascular dysfunction.
Patients with long COVID have persistent dysfunction of the autonomic nervous system, which is the component of our peripheral nervous system that regulates our heart rate, respiration, and other functions.2 This persistent autonomic dysfunction can lead to long COVID symptoms such as fatigue, breathlessness, palpitations, dizziness, and brain fog. As a result, HRV biofeedback can help activate the parasympathetic nervous system and increase cardiac homeostasis, which can reduce the release of inflammatory markers.
What evidence supports the use of HRV biofeedback for long COVID?
Investigations conducted by the European Society of Cardiology evaluated 434 COVID survivors three months after hospital discharge and found alterations in heart rate variability likely explained by autonomic dysfunction.3 HRV biofeedback training improved autonomic functioning and generated better cardiovascular regulation.
There is an ongoing trial in the UK assessing the use of a four-week HRV biofeedback training intervention for long COVID symptoms.4 Overall, HRV biofeedback has been utilized since the 1990s and is a reasonable treatment alternative for long COVID symptoms triggered by autonomic dysfunction.
What should you be aware of with HRV biofeedback?
HRV biofeedback is a safe training method with no serious adverse events reported. Individuals may experience stress when given negative feedback in a session, but there are no other known side effects of HRV biofeedback. HRV biofeedback can also serve as an option for pregnant women who would like a non-pharmacological treatment option for certain long COVID symptoms. Results from a randomized controlled trial indicated a statistically significant beneficial effect on psychological well-being and anxiety for both pregnant and non-pregnant women.5
References:
Alkaline Serine Protease for long COVID
ALKALINE SERINE PROTEASE
What is alkaline serine protease?
Alkaline serine protease is a protease whose primary role is to break down proteins. It can be derived from the Neanthes japonica worm [[1]].
What does alkaline serine protease do in the body?
Alkaline serine protease breaks down proteins in the body. These proteins include inflammatory cytokines, the enzyme thrombin, which causes blood clots, and proteins such as the SARS-CoV-2 spike protein. Because of its anti-spike protein activity, alkaline serine protease represents a natural therapeutic against COVID-19 [[2]].
In animal studies, alkaline serine protease was found not toxic to organs, including the liver, the heart, and the kidneys [[3]].
How can alkaline serine protease help alleviate certain Long COVID symptoms and pathophysiology?
Researchers suggest that alkaline serine protease can act as a scavenger in the body, breaking down spike protein throughout the bloodstream due to its role in breaking down spike proteins. This can be helpful for Long COVID patients who still may have the virus in their system after the acute COVID-19 disease phase. An added feature of alkaline serine protease is that it is not toxic to organs such as the liver, heart, and kidneys, though it can reduce stroke risk [[4]]. Researchers hypothesize that alkaline serine protease can be used to prevent and treat heart and vascular inflammation and injuries resulting from the mRNA COVID vaccine in people with Long COVID [[5]].
Zinc for long COVID
ZINC
What is zinc?
The body needs only minimal amounts of zinc. It is a trace mineral, meaning humans do not produce it naturally. Therefore, we must get zinc from dietary sources or supplementation. Zinc deficiency may be a common feature in infectious diseases; a study found it was the most common deficiency in an infectious disease clinic [[1]]. Zinc deficiency, however, is also generally common worldwide, especially in the Global South nations [[2]]. Insufficient zinc intake is associated with an increased risk of respiratory tract infections, especially in older people [[3]].
What does zinc do in the body?
Zinc’s important roles include cell growth and reproduction, immune function, and metabolism. In addition to being an antioxidant and anti-inflammatory compound, zinc may decrease viral replication. In acute COVID-19 patients, zinc supplementation can improve lung function, improve mucus clearance, and reduce lung injury from ventilators in critical patients. Zinc deficiency may also be associated with anosmia (loss of smell) and dysgeusia (loss of taste), which can last for some time after acute COVID infection [[3]].
How can zinc help alleviate certain Long COVID symptoms and pathophysiology?
Researchers believe a potential reason for the persistence of Long COVID symptoms is that zinc deficiency is not adequately addressed in the conventional “standard of care” [[4]]. Zinc deficiency is linked to acute, persistent inflammation, which is a feature of Long COVID [[5]]. It can also affect certain types of lung cells and decrease lung barrier function [[6]]. Therefore, zinc supplementation may help reduce the body’s inflammatory response in Long COVID, particularly in the lungs.
Hyperbaric Oxygen Therapy for long COVID
HYPERBARIC OXYGEN THERAPY
What is hyperbaric oxygen therapy?
Hyperbaric oxygen therapy involves breathing in 100% oxygen under air pressure two to three times higher than normal air pressure. This allows your lungs to take in more oxygen than they can at normal air pressure. Hyperbaric oxygen therapy is typically an outpatient procedure that can be done in an individual unit for one patient within a chamber or a room for multiple people through a mask. This procedure is often used for wound healing or serious infections, as the extra oxygen can release growth factors and stem cells to promote healing and help fight bacteria.1
How can hyperbaric oxygen therapy help alleviate certain long COVID symptoms?
The mechanisms behind long COVID symptoms are not fully understood. Still, they are believed to be partly due to increased activation of proteins that promote clotting and hyperactive inflammatory and autoimmune responses. Hyperbaric oxygen therapy can improve circulation within our smallest blood vessels, inhibit the release of inflammatory mediators, inhibit autoimmune responses, and promote neurological repair.2 Hyperbaric oxygen therapy is proposed to improve the following long COVID symptoms: chronic fatigue; neurocognitive functions such as energy, sleep, pain, and psychiatric symptoms; and cardiac dysfunction such as shortness of breath.
What evidence supports the use of hyperbaric oxygen therapy for long COVID?
Several randomized control trials have studied the use of hyperbaric oxygen therapy for long COVID. The first evaluation of hyperbaric oxygen therapy for long COVID was a study done with ten patients who each received ten sessions over 12 days, each lasting 105 minutes with three 30-minute exposures to 100% oxygen. The study found a significant improvement in fatigue, cognition, information processing, executive function, attention, and verbal function.3 Another trial with 73 patients randomized to receive hyperbaric oxygen therapy daily for 40 sessions also saw significant improvement in energy, sleep, psychiatric symptoms, and pain.4
Other long-term effects of COVID include cardiac injury, such as inflammation in the heart and increased risk of arrhythmias, heart disease, heart failure, or stroke. One trial looked at the effect of hyperbaric oxygen therapy on cardiac function in long COVID patients in 60 patients randomized to receive 40 daily hyperbaric oxygen therapy sessions or placebo. The outcome of interest was global longitudinal strain (or GLS), which measures how well the heart is pumping blood to the rest of the body. The study found that GLS was significantly increased after hyperbaric oxygen therapy.5
What are some things to watch out for with hyperbaric oxygen therapy?
Hyperbaric oxygen therapy has risks, including middle ear injuries due to the higher air pressure, temporary nearsightedness, lung collapse, seizures (rarely), lowered blood sugar in people treated with insulin for diabetes, and a potential risk of fire.1 It is important to remove any hair or skin products that are petroleum-based, as they can pose a potential fire hazard.
An ongoing trial released interim safety data on 20 patients randomized to receive hyperbaric oxygen therapy or placebo and found that 60% of the participants experienced at least one adverse event.6 The most common adverse events were cough and chest pain or discomfort. All adverse events were temporary. No serious adverse events were reported.
Hyperbaric oxygen therapy cannot be used in patients with a collapsed lung. It should typically not be used in obstructive lung disease or a recent ear or thoracic (chest) surgery.
References:
1) Mayo Clinic Staff. Hyperbaric oxygen therapy. Mayo Clinic. Nov 4, 2022. Accessed November 5, 2023. https://www.mayoclinic.org/tests-procedures/hyperbaric-oxygen-therapy/about/pac-20394380
Active Clinical Trials: Long COVID, Hyperbaric oxygen | Card Results | ClinicalTrials.gov
Alpha-Lipoic Acid for long COVID
ALPHA-LIPOIC ACID
What is alpha-lipoic acid?
Alpha-lipoic acid, or ALA, sometimes called thiotic acid, is a fatty acid used as a supplement for many different health conditions. It is widely distributed in human cells across various cell types and is involved in producing energy [[1]].
What does alpha-lipoic acid do in the body?
ALA helps enzymes control metabolism and energy production and grow and develop new mitochondria [[1]]. It is also an antioxidant and anti-inflammatory substance. It is involved in controlling glucose levels, reducing oxidative stress in the body, and maintaining an antioxidant balance [[2]]. It is also known for its roles in preventing diabetic neuropathy and scavenging and neutralizing free radicals [[3]].
How can alpha-lipoic acid help alleviate certain Long COVID symptoms and pathophysiology?
ALA’s effects can help reduce damage to the body’s cells and tissues that occurs with COVID-19. Evidence shows that SARS-CoV-2, the virus that causes COVID-19, causes dysfunction in the body’s endothelial tissues, such as the lining of blood cells. Endothelial dysfunction includes oxidative stress, leading to endothelial cell injury. Functioning endothelial tissues are needed for cardiovascular health. ALA can reduce oxidative stress in the endothelial system, improving endothelial function. Therefore, it may counteract the endothelial damage in Long COVID [[3]].
ALA also improves mitochondrial function, helping new mitochondria develop, which makes energy expenditure more efficient on the cellular level, supporting the health of the body’s tissues. Lastly, by boosting glutathione, ALA can serve as an indirect means to support immune function [[3]].
Serrapeptase for long COVID
SERRAPEPTASE
What is serrapeptase?
While more research is needed to better understand serrapeptase, a few things are known about this compound, which is produced naturally within the intestines of silkworms [[1]]. Serrapeptase is a protease that breaks down proteins into amino acids, the building blocks of proteins. Silkworms use the compound to break down their cocoons when born [[2]]. Serrapeptase is also known as serratiopeptidase, serratiopeptidase, serralysin, and others [[1]].
What does serrapeptase do in the body?
Serrapeptase is known for its robust anti-inflammatory activity. As an analgesic (pain reliever), it can be used by itself or in conjunction with other drugs to treat inflammation, positioning it as an alternative to traditional non-steroidal anti-inflammatory drugs (NSAIDs), boasting fewer side effects. It has been used to treat chronic sinusitis, carpal tunnel syndrome, sprains, torn ligaments, and post-operative inflammation [[2]]. It is also an anti-edemic compound, meaning it prevents the abnormal collection of fluid in body tissues and the circulatory system. It is also fibrinolytic, meaning that it can eliminate fibrous scarring. It is also mucolytic, which breaks up mucus to help the lungs breathe more easily [[3]].
How can serrapeptase help alleviate certain Long COVID symptoms and pathophysiology?
Serrapeptase can be used as an anti-inflammatory, analgesic, and anti-edemic compound for patients with Long COVID. In the respiratory tract of Long COVID patients, serrapeptase’s mucolysis can help improve respiratory tract health by strengthening immune defenses. Lastly, anti-inflammatory effects can be beneficial for Long COVID patients as well. More data is needed to examine safety, tolerability, and mechanism of action [[2]].
Cimetidine for long COVID
CIMETIDINE
What is cimetidine?
Cimetidine is an H2-antihistamine used for heartburn, stomach ulcers, and acid reflux. It blocks histamine-2 receptors in the stomach, preventing the stomach from secreting as much acid. Famotidine (another H2-antihistamine in the same drug class) may be preferred over cimetidine due to its longer duration of action and higher potency.
How can cimetidine help alleviate certain long COVID symptoms?
Histamine is a chemical our immune system releases that causes allergy symptoms. Cells in our body called mast cells release histamine, and in some patients after COVID, they may release too much, leading to some of the symptoms of long COVID. Two types of drugs can block histamine in the body: H1- and H2-antihistamines, like cimetidine. Blocking histamine can lead to anti-inflammatory effects that cimetidine could theoretically be used for to relieve pulmonary and cardiovascular symptoms of long COVID.
What evidence supports cimetidine’s use for long COVID?
Cimetidine has been found to exhibit binding affinity to the SARS-CoV-2 virus that could result in some antiviral activity on a molecular level.1 However, human studies have not shown cimetidine to have protective properties against an active COVID infection; thus, it should not be used to treat it.2
There is a lack of evidence supporting cimetidine’s use for long COVID symptoms. Several studies have instead looked at the use of famotidine for the relief of cardiovascular and neurologic symptoms of long COVID, such as a fast heart rate, brain fog, and chest pain.3 While these two drugs are very similar, it is believed that famotidine has a unique non-histamine receptor-mediated property that cimetidine does not possess that allows it to relieve certain COVID symptoms.2 Therefore, it is likely more efficacious to trial famotidine instead.
What should you be aware of when taking cimetidine?
Although uncommon, cimetidine can cause headaches, dizziness, and drowsiness. It can also have some anti-androgenic effects at high doses, which, in rare cases, may cause enlarged breast tissue in men (also known as gynecomastia). Cimetidine may have more interactions with other drugs you may take compared to famotidine, so you should let your doctor or pharmacist know if you are frequently taking cimetidine.
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