Simvastatin for long COVID
SIMVASTATIN
What is simvastatin (Zocor)?
Simvastatin is part of a class of drugs commonly referred to as statins. Its role is to reduce the amount of cholesterol the liver makes. Cholesterol comprises HDL, the “good” cholesterol, and LDL, the “bad” cholesterol. The body uses cholesterol to make various hormones and other substances. However, if a person has too much LDL, it can cause a buildup in the arteries, leading to stroke, heart attack, or other health problems.
How does simvastatin relate to long-COVID?
Simvastatin possesses anti-inflammatory and modifying effects on the immune system (1). A recent study conducted in vitro (in test tubes) showed that simvastatin reduced levels of pro-inflammatory proteins and inhibited human cells from being infected with COVID-19 (2). However, statins can also upregulate or increase an enzyme called ACE2. ACE2 is how COVID-19 makes its way into the cells, leading to an influx of disease ( 3).
For those who suffer from long-COVID, the effects of statins may prolong illness even further. Highlights of long-COVID include chronic fatigue, exercise intolerance, and muscle weakness. Muscle weakness or muscle pain (myalgia) is also a primary side effect associated with the use of statins. Therefore, many believe that statins are exaggerating long-COVID in patients. Additionally, statins can decrease the amount of CoQ10 available for use by the body. CoQ10 is an antioxidant that has a role in the cells’ energy production (4). For those suffering from long-COVID and already with a decreased energy reserve, statin use could only exacerbate this problem further.
Although currently, there is no definitive answer regarding the role of simvastatin use in patients with long-COVID, the consensus is to aid on the side of caution. A benefit versus risk scenario for every patient should be warranted for providers to assess whether the cardio-protective use of statins outweighs the prolonged effects of long-COVID in patients.
References:
1https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9520195/
2https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1011050
3https://jamanetwork.com/journals/jama/fullarticle/2780872
4 https://www.mdpi.com/2077-0383/12/14/4659
Chlorpheniramine for long COVID
CHLORPHENIRAMINE
What is chlorpheniramine?
Chlorpheniramine is an antihistamine that relieves symptoms of allergies, hay fever, or a cold, such as red, itchy, or watery eyes, sneezing, and runny nose. Compared to other antihistamines, chlorpheniramine is more sedating and can help you fall asleep. It is typically taken as a 4 mg tablet every 4-6 hours for adults and children ages 12 years and older.
How can chlorpheniramine help alleviate certain long COVID symptoms?
Histamine is a chemical our immune system releases that causes our 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. Long COVID is believed to be a state of prolonged hyper-inflammation that follows the infection. Chlorpheniramine can block histamine type 1 receptors and help alleviate nasal congestion and inflammatory symptoms of long COVID.
What evidence supports chlorpheniramine’s use for long COVID?
In vitro, chlorpheniramine has been found to have antiviral properties by blocking viral replication and directly inactivating the COVID virus and other respiratory viruses such as influenza.1 While a chlorpheniramine nasal spray is not currently available over-the-counter in the US, it has been studied in patients treated outpatient with mild to moderate COVID and was found to reduce symptoms by day seven and specifically improve nasal congestion.2 In this study, 136 patients were randomized to chlorpheniramine nasal spray for ten days or placebo. It is important to note that chlorpheniramine nasal spray results may differ from oral chlorphenamine tablets because the medications are absorbed differently and applied at different sites of action.
Antihistamines are effective in managing long COVID symptoms.3 Other H1-antihistamines such as fexofenadine, loratadine, and cetirizine have beneficial effects on long COVID symptoms, and chlorpheniramine would likely show similar effects.4,5 However, more studies that look specifically at chlorpheniramine for long COVID are needed.
What are some things to watch out for with chlorpheniramine?
Because chlorpheniramine can cause drowsiness, it should not be taken during the day, while driving, or while operating heavy machinery. Depending on what other medications you take, chlorpheniramine can worsen some side effects, such as constipation, dry mouth, and dry eyes. While chlorpheniramine has sedating effects, it should not be routinely used for insomnia.
References:
Hydroxyzine
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Modafinil for long COVID
MODAFANIL
What is modafinil (Provigil) used for?
Modafinil is commonly prescribed for narcolepsy and shift-work sleep disorder. It is a central nervous system (CNS) stimulant in that its effects are within the brain and spinal cord; however, it has a low potential for abuse, unlike Adderall or Vyvanse, due to its pharmacokinetic properties [1].
How can modafinil help patients dealing with long-COVID?
Researchers’ theory in long-COVID says that pathways in the brain become distorted. The initial infection caused by COVID-19 increases inflammation in the brain, leaving the cells vulnerable to other organisms or substances that may also cause inflammation. This cycle continues and destroys the signaling pathways between the cells in the brain. Over time, this results in the death of brain cells, leading to “brain fog.” Since those with long-COVID suffer from inflammation, armodafinil may assist in rebuilding the destroyed pathways, leading to increased concentration and memory [1].
Additionally, modafinil is a CNS stimulant that can promote wakefulness and decrease fatigue, something long-COVID sufferers are all too familiar with [2]. Although more research needs to be completed regarding the use of modafinil for long-COVID, it does show promise in helping patients struggling with concentration, memory, and fatigue problems.
References:
1https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp-rj.2022.170402
2https://journals.sagepub.com/doi/pdf/10.1177/10398562211003598
Umeclidinium/vilanterol for long COVID
UMECLIDINIUM/VILANTEROL
What is umeclidinium/vilanterol (Anoro Ellipta)?
Umeclidinium/vilanterol is part of a class of medications used to treat the inflammatory respiratory condition of chronic obstructive pulmonary disease (COPD). It contains an anticholinergic, umeclidinium, and a bronchodilator, vilanterol. Both medications are used to help open and relax the airways, making it easier to breathe.
How can umeclidinium/vilanterol be used to treat long-COVID?
Patients with long-COVID have symptoms such as chronic fatigue, pulmonary problems, and exercise intolerance. Due to umeclidinium/vilanterol’s mechanism of action in opening the airways, those suffering with breathing issues from long-COVID may be positively impacted. Although no formal studies have been conducted to determine how effective this treatment is, patients have reported positive results [1]. Umeclidinium/vilanterol is not indicated for the treatment for long-COVID but could provide symptom management by increasing lung capacity, exercise intolerance, and decreasing inflammation in the lungs.
References:
1 https://healthunlocked.com/asthmalunguk-lung/posts/147776793/anoro-ellipta-have-you-had-side-effects /
Pitavastatin
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Molnupiravir for long COVID
MOLNUPIRAVIR
What is molnupiravir (Lagevrio)?
Molnupiravir, a medication authorized by the FDA in 2021 for Emergency Use, is used to treat COVID-19 infections [1]. It is an antiviral that changes the genetic makeup of COVID-19, so it cannot replicate. For the best outcome, molnupiravir should be used within five days of symptom onset.
How can molnupiravir help with long-COVID?
Currently, there is some evidence supporting the use of molnupiravir to decrease the risk of long-COVID. In a clinical study completed in 2021, patients treated with molnupiravir had faster tissue oxygen saturation times and a reduced demand for respiratory aid [2]. Long-COVID is often characterized by symptoms such as fatigue, shortness of breath, and exercise intolerance; these findings indicate molnupiravir decreases respiratory symptoms, allowing patients to return to pre-COVID baselines quicker [3]. A second study completed by the Veterans Affairs (VA) found that those who received molnupiravir within five days of having symptoms had a reduced risk of adverse outcomes after six months. It did not matter if a person was unvaccinated, partially vaccinated, or unvaccinated; the outcomes were positive regardless of vaccination status [4].
Molnupiravir as a treatment for COVID-19 has been established; however, for prevention of long-COVID, the status remains unknown. It shows promise in decreasing symptoms early on in COVID-19. However, further research can help to solidify its use for patients with long-COVID.
References:
2https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10029330/
4https://www.bmj.com/content/381/bmj-2022-074572
Venlafaxine for long COVID
VENLAFAXINE
What is venlafaxine (Effexor)?
Most used for anxiety and depression, venlafaxine belongs to a class of medication called serotonin-norepinephrine reuptake inhibitors (SNRIs). 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]. In conditions like depression and anxiety, the brain is dealing with an imbalance of chemicals such as serotonin and norepinephrine. SNRIs, like venlafaxine, keep serotonin and norepinephrine in a space where they can readily be used for bodily processes.
How can venlafaxine help with long-COVID?
In those diagnosed with long-COVID, many suffer from “brain fog”; decreased cognitive acuity, memory deficits, poor focus, reduced ability to multitask, and reduced concentration [2]. The proposed reason is that during a COVID-19 infection, the body’s immune response becomes activated, causing heavy amounts of inflammation. This inflammation affects the central nervous system (CNS), brain, and spinal cord. To combat this problem, researchers have turned to already existing medication therapies in the hopes they may be able to help decrease “brain fog” symptoms. Although studies have been completed in humans regarding venlafaxine’s effect in long-COVID, lab data has shown promise.
Serotonin and norepinephrine have been shown to have an effect against viral inflammation by blocking certain viruses (like HIV-1) into the cells. In addition, they can decrease cytokine production, promoting the immune response [3]. Since serotonin and norepinephrine possess anti-inflammatory properties and may inhibit viral activity, venlafaxine could be an option for treating long-COVID. Venlafaxine keeps these chemicals around longer in the body to perform their functions; therefore, if they are active longer, the immune response and symptoms of depression may decrease.
Further research needs to be conducted in clinical trials to assess the effectiveness of venlafaxine for treating long-COVID; however, for symptom management of depression, venlafaxine may be an option for patients.
References
1https://my.clevelandclinic.org/health/articles/22572-serotonin
2https://americanaddictioncenters.org/antidepressants-guide/ndris
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