Paxlovid (Nirmatrelvir/Ritonavir) for long COVID
PAXLOVID(NIRMATRELVIR/RITONAVIR)
What is Paxlovid?
The FDA approved Paxlovid in December 2021 for the acute treatment of COVID-19. According to current guidelines, it is most efficacious if used within the first five days of infection. Paxlovid is a combination of two antiviral medications, nirmatrelvir, and ritonavir, which inhibit the virus’s replication in cells.
What can Paxlovid do for those with long-COVID?
Recently, there has been evidence that Paxlovid may be beneficial in reducing the possibility of developing symptoms associated with long COVID [1] Researchers found it did not matter whether the patient had a recurrence of COVID-19 or whether they were vaccinated. By taking Paxlovid within the first five days of a COVID-19 diagnosis, the potential to develop long-COVID diminished [2].
Additionally, for those already diagnosed with long-COVID, it is possible that Paxlovid, taken for a duration longer than five days, may help to reduce long-COVID symptoms further. The notion behind this theory points to COVID-19 viral shedding. In long-COVID, although a person does not have an active infection, the virus may still be shedding in the body, leading to an upregulation by the immune system [3]. This upregulation leads to an immune response characterized by fatigue, lightheadedness, trouble breathing, and exercise intolerance. Although more research needs to be conducted regarding the extension of Paxlovid past its recommended duration of use, current results are mixed. A recent study showed that a 15-day course of Paxlovid did not improve long COVID symptoms it does show promise in alleviating the symptoms of long-COVID for patients.
References:
3https://www.ucsf.edu/news/2022/05/422771/covid-drug-may-also-ease-symptoms-long-covid
Active Clinical Trials: Long COVID, nirmatrelvir | Card Results | ClinicalTrials.gov
Aspirin for long COVID
ASPIRIN
What is aspirin?
Aspirin is an antiplatelet agent that is commonly used for the prevention of blood clots and secondary prevention of cardiovascular disease after patients have a stroke or heart attack. It is often taken indefinitely in these cases at a low dose of 81 mg, also known as baby aspirin. Aspirin has many strengths, and its drug properties vary depending on the dosage. At higher doses greater than 325 mg every 4-6 hours, it serves as a non-steroidal anti-inflammatory drug (NSAID) that can be used to relieve pain and reduce fever.
How can aspirin help alleviate certain long COVID symptoms?
An acute COVID infection can lead to hyperactivated platelets and damaged red blood cells, making it more likely for the body to form a clot. Patients from South Africa with long COVID have been found to have amyloid deposits in their blood samples called microclots.1 It is believed that these microclots can prevent oxygen from adequately reaching all of our tissues, which may cause long COVID symptoms. Aspirin works by irreversibly inhibiting enzymes called COX-1 and COX-2 that are needed for platelets (cells in our blood that form clots) to aggregate and activate. Thus, agents that prevent clots may play a role in helping people experiencing long COVID symptoms such as fatigue, brain fog, loss of concentration, shortness of breath, and joint and muscle pains.
What evidence supports aspirin’s use for long COVID?
The use of aspirin within the first day of hospitalization for moderate COVID was associated with lower odds of in-hospital mortality within 28 days. However, the absolute difference in mortality rates for the treatment vs placebo group was slight.2
A study done in South Africa treated 24 patients with a combination of clopidogrel 75 mg (an antiplatelet agent), aspirin 75 mg daily, and a direct oral anticoagulant apixaban (Eliquis) 5 mg twice a day. A proton pump inhibitor, pantoprazole, was also added to prevent gastrointestinal ulcers or bleeding. All patients reported that their main fatigue symptoms were resolved, as well as their other long-term COVID symptoms.3 It is important to note, however, that this study was not placebo-controlled and has not yet been peer-reviewed for publication. This treatment combination also puts patients at high risk of bleeding and is not recommended for certain patients and demographics.
While aspirin does have beneficial effects in preventing blood clots, aspirin alone may not be sufficient for the breakdown of microclots. Increased risks of bleeding with aspirin should also be taken into consideration when asking your doctor about treatments for long COVID.
What should you be aware of when taking aspirin?
Aspirin is associated with a 2- to 4-fold increase in upper gastrointestinal (GI) events ranging from indigestion to GI ulcers or bleeding. The use of enteric-coated aspirin does not necessarily decrease this risk. Some people can have immediate or delayed allergic reactions to aspirin, leading to anaphylaxis, which can be serious in some rare cases. Because of its antiplatelet effects, it can cause you to bleed more easily, especially if you are taking other blood thinners or medications/supplements that can increase your risk of bleeding.
Large doses of aspirin (greater than 325 mg daily) should be avoided for long-term use, especially in people with chronic kidney disease, heart failure, cirrhosis, older adults, or those taking diuretics (also known as water pills). Even if you are taking baby aspirin, it is important to let your doctor know you are on this medication.
References:
Naproxen
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Indomethacin for long COVID
INDOMETHACIN
What is indomethacin (Indocin)?
Indomethacin belongs to the class of medications called non-steroidal anti-inflammatory drugs (NSAIDs). Other drugs found within this class are diclofenac (Voltaren), meloxicam (Mobic), ibuprofen (Advil), and naproxen (Naprosyn). Indomethacin and other NSAIDs work by inhibiting the compounds responsible for inducing inflammation [1].
What is the link between indomethacin and long-COVID?
Many patients diagnosed with long-COVID are plagued by moderate to severe, frequent headaches. The cause is thought to be massive inflammation accompanied by a cytokine storm (overexaggeration of the immune system) [2]. These headaches can worsen a preexisting primary headache or, more specifically, present as a new (intermittent or daily) headache starting during the acute infection or after a delay [2].
To treat these headaches, providers have begun using indomethacin. A study was conducted in 37 patients, and 36 of those patients’ use of indomethacin reduced headaches by more than 50% on day 3 with complete resolution on day 5 [3]. In another study comparing paracetamol (acetaminophen/Tylenol) to indomethacin, the indomethacin group experienced quicker symptom relief and complained only of tiredness as a side effect [4].
Although indomethacin will not cure long-COVID, it may offer symptom management in headache sufferers. Indomethacin is relatively safe and has shown effectiveness in patients where other therapies have failed, making it an attractive option for those dealing with headaches from long-COVID.
References:
2https://thejournalofheadacheandpain.biomedcentral.com/articles/10.1186/s10194-022-01450-8
3https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8453033/
4https://www.nature.com/articles/s41598-022-10370-1
Paroxetine for long COVID
Paroxetine (Paxil)
What is paroxetine (Paxil)?
Most used for anxiety and depression, paroxetine belongs to a class of medication called selective serotonin reuptake inhibitors (SSRIs). 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. In conditions like depression and anxiety, the brain is dealing with an imbalance of chemicals such as serotonin. SSRIs, like paroxetine, work by keeping serotonin in the space where it can readily be available for bodily processes.
What is the connection between paroxetine and long-COVID?
Serotonin has been shown to have an effect against viral inflammation by blocking certain viruses (like HIV-1) into the cells. In addition, it can decrease cytokine production, promoting the immune response [2]. 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.
Researchers have begun looking at paroxetine as a potential agent to treat long-COVID and depression associated with long-COVID. A trial conducted on 60 patients showed a decrease in depression when treated with an SSRI, such as paroxetine [2]. In addition, a study looking at 95 patients found the addition of SSRIs, including paroxetine, led to an improvement in well-being in those with long-COVID [3].
More research needs to be conducted as there is currently limited evidence to support the use of SSRIs for inflammation-related long-COVID; however, for symptoms of depression associated with long-COVID, paroxetine may be a viable option [4]. Paroxetine is currently listed on long-COVID clinical guidelines for the treatment of depression. With further clinical studies, its indication could potentially expand to include the eradication of long-COVID [5].
References:
1 https://my.clevelandclinic.org/health/articles/22572-serotonin
3https://www.nature.com/articles/s41598-023-45072-9
4https://link.springer.com/article/10.1007/s40267-022-00975-x
Active Clinical Trials: Long COVID, SSRI | Card Results | ClinicalTrials.gov
Azelastine Nasal Spray for long COVID
AZELASTINE NASAL SPRAY
What is azelastine?
Azelastine is an over-the-counter antihistamine nasal spray for seasonal or year-long allergy symptoms such as nasal congestion, a runny nose, sneezing, itching, and post-nasal drip. It can be given as one or two sprays in each nostril twice a day and is a suitable antihistamine option with fewer side effects compared to oral antihistamines.
How can azelastine 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. Two types of drugs can block histamine in the body, which we call our H1- and H2-antihistamines. Azelastine is an example of an H1-antihistamine that has also been found to bind to the ACE-2 and sigma-1 receptors in the nasal epithelium.1,2 This may inhibit the SARS-CoV-2 virus from binding to ACE-2 and replicating intracellularly. As an antihistamine, azelastine’s anti-inflammatory properties can also aid in relieving nasal symptoms of long COVID.
What evidence supports azelastine’s use for long COVID?
In several studies, Azelastine has shown antiviral activity against COVID in vitro and a more significant reduction in viral load compared to placebo.2 Intranasal azelastine has also demonstrated a faster decline in symptom severity compared to placebo in COVID patients.3 While antihistamines as a whole have been extensively studied for long COVID symptoms, there is a lack of studies specifically evaluating the use of azelastine post-COVID. Therefore, azelastine may not be as effective for long COVID symptoms compared to oral H1-antihistamines such as fexofenadine.
What should you be aware of when taking azelastine?
Azelastine nasal spray may cause nasal irritation, sore throat, headache, or drowsiness. Some may also complain that it has a bitter aftertaste.
References:
Fluticasone Nasal
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Leronlimab for long COVID
LERONLIMAB
What is leronlimab?
Leronlimab is a medication used to treat the human immunodeficient virus (HIV). It works by blocking the entry of HIV into cells, halting the virus’s replication [1]. The FDA does not approve Leronlimab, which is currently an investigational product. The timing of FDA approval is currently unknown.
Can leronlimab be used in long-COVID?
Since leronlimab is an antiviral medication, researchers theorize it may play a role in treating long-COVID. Patients with long-COVID often deal with symptoms such as fatigue, shortness of breath, and cognitive dysfunction. These symptoms may occur following initial recovery from a COVID-19 episode or persist from the initial illness [2]. Although not actively infected, patients with long-COVID are thought to shed the virus in the body continuously. This constant shedding leads to an overresponse of the immune system, causing increased inflammation.
Leronlimab is thought to bind to a protein that increases inflammation. This binding helps regulate the immune response to COVID-19, thereby slowing inflammation [3]. One study concluded that the immune response normalized in patients treated with leronlimab [4].
Further research needs to be conducted to prove the use of leronlimab in long-term COVID; however, early studies show promise. Leronlimab, unlike other therapies that only treat symptoms, may help eradicate the virus from the body.
References:
1https://clinicalinfo.hiv.gov/en/drugs/leronlimab/patient
3https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277229/
4https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9659683/
Pitavastatin for long COVID
PITAVASTATIN
What is pitavastatin (Livalo)?
Pitavastatin is part of a class of drugs commonly referred to as statins. Its role is to reduce the amount of cholesterol made by the liver. Cholesterol is comprised of 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 pitavastatin relate to long-COVID?
Pitavastatin 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 cell 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 pitavastatin 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
Active Clinical Trials: Long COVID, statin | Card Results | ClinicalTrials.gov
Brain HQ for long COVID
BRAIN TRAINING PROGRAMS: BRAIN HQ
What are brain training programs like BrainHQ?
BrainHQ is an interactive online program that offers a variety of exercises to help train the brain to improve cognitive tasks such as memory, attention, and speed.1 Tasks adapt to a level of difficulty that is optimal for the user. Each level takes less than five minutes to complete. BrainHQ has 29 online exercises for attention, brain speed, memory, people skills, navigation, and intelligence. Users can customize their exercises to their needs and schedule. BrainHQ is available as a free online resource at various libraries in the US.
How can brain training programs like BrainHQ help alleviate certain long COVID symptoms?
Cognitive symptoms of long COVID include brain fog (trouble thinking clearly or remembering) and difficulty focusing on tasks. The SARS-CoV-2 virus can directly infect the central nervous system and damage brain tissue, which is hypothesized to lead to cognitive impairment. In addition, the virus possesses a spike protein that studies have associated with memory loss after COVID.2 This spike protein can activate neuroinflammation and ultimately lead to memory impairment.
Brain training programs like BrainHQ are intended to promote brain plasticity, which rewires the brain to make physical changes that improve learning. BrainHQ exercises can increase the activation of brain regions for specific cognitive functions and build neural connections over time.3
What evidence supports using brain training programs like BrainHQ for long COVID?
Studies using BrainHQ exercises and assessments have found benefits such as faster visual and auditory processing, better memory, faster neural timing, fewer dangerous driving moves, and better mood. BrainHQ has been used in hundreds of published studies for a wide range of conditions such as ADHD, autism spectrum disorder, bipolar, dementia, depression, diabetes, heart failure, MS, Parkinson’s, schizophrenia, and more.4 For instance, BrainHQ has been studied in breast cancer survivors and showed improvements in immediate and delayed memory and speed of processing.5
The RECOVER-NEURO trial is actively recruiting to investigate BrainHQ as a possible treatment to improve memory, attention, and brain processing speed for long COVID patients. It is also being studied with an online goal management training program or transcranial direct current stimulation to increase activity in specific brain parts.6
In summary, BrainHQ is an extensively studied brain training program that has shown benefits in cognitive function. Ongoing research will help to determine its effectiveness for long COVID patients.
References:
1) Brain Training That Works. BrainHQ. 2023. Accessed November 8, 2023. https://www.brainhq.com/?utm_source=google&utm_medium=cpc&utm_campaign=brand&utm_content=46467711%2B327060831330&utm_term=brainhq&gad=1&gclid=Cj0KCQiAgK2qBhCHARIsAGACuznJ-tHxC4VThBFhINIfiVtv6u6_fD8D7r0ROAIYzFvqR12JHHWXlVoaAumfEALw_wcB&v4=true&fr=y
3) The Proven Benefits of BrainHQ. BrainHQ. 2023. Accessed November 8, 2023. https://www.brainhq.com/world-class-science/the-proven-benefits-of-brainhq/
4) Hundreds of Published Studies. BrainHQ. 2023. Accessed November 8, 2023. https://www.brainhq.com/world-class-science/information-researchers/
5) Evidence-Based Cancer Control Programs (EBCCP). National Cancer Institute. March 29, 2023. Accessed November 8, 2023. https://ebccp.cancercontrol.cancer.gov/programDetails.do?programId=27852796
6) RECOVER-NEURO Clinical Trial. RECOVER: Researching COVID to Enhance Recovery. 2023. Accessed November 8, 2023. https://trials.recovercovid.org/neuro
Active Clinical Trials: Long COVID, brain training | Card Results | ClinicalTrials.gov
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