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Methylprednisolone for long COVID
METHYLPREDNISOLONE
What is methylprednisolone (Medrol)?
Corticosteroids, often called steroids, are a class of medication used to decrease inflammation. Steroids, like methylprednisolone, reduce the production of chemicals that cause inflammation [1]. They are used in a variety of disease states when inflammation is abundant. Steroids should be used for the shortest duration and lowest dose possible and should not be stopped abruptly. Doing so could lead to withdrawal symptoms or a flare-up if used for an autoimmune condition such as rheumatoid arthritis.
Can methylprednisolone treat long-COVID?
Patients dealing with symptoms of long-COVID may see some beneficial results with the use of methylprednisolone. In long-COVID, it is theorized that the body is under constant inflammation via a cytokine storm, an overresponse of the immune system. Although a person is not actively infected with COVID-19, the body still sheds the virus. Since COVID-19 is a foreign material, the immune response is invoked, resulting in inflammation [2]. Since methylprednisolone decreases inflammation, it could alleviate some of the symptoms of long-COVID, such as “brain fog, chronic fatigue, and exercise intolerance.
Although few studies have tested methylprednisolone’s effectiveness in treating long-COVID, the limited results show promise. In one study on 14 patients, researchers looked at the immune response before and after four-day treatment with steroids. Results showed the immune response decreased and was maintained for at least four months following therapy [2]. A second study found that treatment with tapering steroids improved breathing, increased oxygen levels, and decreased inflammation on chest X-rays [3].
Methylprednisolone may offer symptom improvement for patients suffering from side effects of long-COVID. However, there has been no evidence it treats the disease state itself. It may be an attractive option to patients as it is relatively affordable and, for a short duration, may help with lung capacity and oxygen levels. A conversation with a healthcare provider can offer additional insight as to whether methylprednisolone would be a potential therapy option for long-COVID.
References:
1https://my.clevelandclinic.org/health/drugs/4812-corticosteroids
3https://pubmed.ncbi.nlm.nih.gov/34730322/
Active Clinical Trials: Long COVID, Methylprednisolone | Card Results | ClinicalTrials.gov
Rosuvastatin for long COVID
ROSUVASTATIN
What is rosuvastatin (Crestor)?
Rosuvastatin is part of a class of drugs commonly referred to as “statins,” whose role is to reduce the amount of cholesterol the liver makes. Cholesterol comprises HDL, the “good” cholesterol, and LDL, the “bad” cholesterol. It is used by the body to produce 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 rosuvastatin relate to long-COVID?
Rosuvastatin 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 rosuvastatin 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
Cannabidivarin (CBDV) for long COVID
CANNABIDIVARIN
What is cannabidivarin?
Cannabidivarin, or CBDV, is a cannabinoid product derived from the cannabis plant that is closely related to CBD but has a slight difference in its chemical structure. This change in chemical structure allows CBDV to have unique effects on the body that are not found with CBD. CBDV can be used for similar indications as CBD, such as epilepsy and nausea; however, it should not be expected to have the same effects as CBD.
How can cannabidivarin help alleviate certain long COVID symptoms?
Interestingly, out of the cannabinoids, only cannabidiol is a potent inhibitor of the SARS-CoV-2 virus. Despite its structural similarity, CBDV has not been found to inhibit COVID infection as potently as CBD.1 In addition, while researchers at the University of Chicago conducted an analysis demonstrating that patients taking CBD tested positive for COVID at significantly lower rates, this finding did not extend to CBDV or other closely related cannabinoids of CBD.2 Thus, the use of CBDV for long COVID symptoms is uncertain.
CBDV also does not activate cannabinoid receptors, making it less effective in pain relief compared to CBD. On the other hand, CBDV blocks a receptor called toll-like receptor 4 (TLR4), which regulates the activation of immune cells and is a target for treating inflammation.3 The SARS-CoV-2 virus can directly infect the brain and cause inflammation in the central nervous system. Thus, CBDV may have beneficial effects on reducing neuroinflammation caused by long COVID with potential downstream impacts on cognitive symptoms of long COVID.
What evidence supports the use of cannabidivarin for long COVID?
CBDV is currently being studied to determine its potential use for various conditions. A study in children with autism spectrum disorder is looking to assess the effects of CBDV on mood, social, and cognitive functions.4 CBDV has also been studied for neuropathic pain in HIV patients and was not found to have beneficial effects on pain relief when given at 400 mg per day for four weeks.5 Other studies have also not found significant reductions in pain with CBDV.6
However, an in vitro and in vivo study found that CBDV can block pro-inflammatory factors activated by downstream effects of TLR4 signaling and specifically improves pain relief in the setting of morphine use.3 This suggests that CBDV may reduce neuroinflammation in long COVID, but further human studies are needed to assess its efficacy.
What are some things to watch out for with cannabidivarin?
No serious adverse events have been reported from trials. CBDV is often well-tolerated but can cause side effects such as diarrhea, dizziness, drowsiness, headache, and nausea.7 It is important to remember that the FDA does not approve CBDV products, and the quality and purity of these products may vary. CBDV can also have drug interactions with many medications, including blood thinners, anti-epileptic drugs, antidepressants, opioids, statins, certain blood pressure medications, and more. It is important to tell your doctor or pharmacist if you are taking CBD regularly to see if there are any potential drug interactions with your other medications.
References:
2) Reyer M. Researchers recommend clinical trials for CBD to prevent COVID-19 based on promising animal data. UChicagoMedicine. January 20, 2022. Accessed November 10, 2023. https://www.uchicagomedicine.org/forefront/research-and-discoveries-articles/researchers-recommend-clinical-trials-for-cbd
4) Hollander E. Cannabidivarin (CBDV) versus placebo in children with autism spectrum disorder. Defense Technical Information Center. August 1, 2020. Accessed November 10, 2023. https://apps.dtic.mil/sti/citations/AD1113593
7) Bauer BA. What are the benefits of CBD – and is it safe to use? Health Lifestyle Consumer Health. Mayo Clinic. December 6, 2022. Accessed November 10, 2023. https://www.mayoclinic.org/healthy-lifestyle/consumer-health/expert-answers/is-cbd-safe-and-effective/faq-20446700#:~:text=Though%20it%27s%20often%20well%2Dtolerated,dosage%20of%20CBD%20in%20products
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Metoprolol for long COVID
METOPROLOL
What is metoprolol?
Metoprolol, a class of medication 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. Metoprolol is referred to as a cardioselective beta blocker; its effects are mostly seen within the heart and not in the other areas of the body.
What is the link between metoprolol and 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 also 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 metoprolol and long-COVID; however, the positive evidence recently discovered provides hope that it may be useful for patients.
References:
2https://doi.org/10.3389/fimmu.2021.749291
Active Clinical Trials: Long COVID, metoprolol | Card Results | ClinicalTrials.gov
Sertraline for long COVID
SERTRALINE
What is sertraline (Zoloft)?
Most used for anxiety and depression, sertraline 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. 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 sertraline, work by keeping serotonin in the space where it can readily be available for bodily processes.
What is the connection between sertraline and 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. Researchers have found some evidence that sertraline may help mitigate symptoms.
Serotonin has also 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]. A trial conducted on 60 patients showed a decrease in depression when treated with an SSRI. Many patients were prescribed sertraline, and 55 showed positive clinical outcomes [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, sertraline may be a viable option [4].
References:
2https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8500775/
3https://link.springer.com/article/10.1007/s40267-022-00975-x
Cetirizine for long COVID
CETIRIZINE
What is cetirizine?
Cetirizine is an over-the-counter antihistamine used to relieve allergy symptoms such as watery or itchy/red eyes, an itchy nose, sneezing, and hives. While it is a non-drowsy antihistamine, it is considered more sedating than fexofenadine (Allegra) or loratadine (Claritin) and is typically taken at 10 mg once a day.
How can cetirizine 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 a prolonged inflammatory response.
Long COVID is believed to be caused by a persistent hyper-inflammatory state that results in symptoms such as fatigue, arthralgia, myalgia, shortness of breath, chest pain, and rash. Two types of drugs can block histamine in the body, which we call our H1- and H2-antihistamines. Cetirizine is an H1-antihistamine believed to reduce inflammatory effects associated with long COVID.
What evidence supports cetirizine’s use for long COVID?
Several studies have shown a benefit in combining an H1- and H2-antihistamine for long COVID symptoms; however, studies need to study cetirizine in long COVID specifically. Loratadine is an H1-antihistamine that works like cetirizine to block histamine in the body. Studies with loratadine in combination with an H2-antihistamine such as famotidine have shown a reduction in long COVID symptoms such as brain fog and headaches, chest pain, and fatigue.1 Given their similarities in mechanism, cetirizine may have similar effects in long COVID patients, but more studies are needed to confirm this.
Cetirizine has been studied in hospitalized patients with an acute COVID infection. A study done with 110 hospitalized COVID-19 patients who received cetirizine 10 mg twice a day plus famotidine (an H2-antihistamine) 20 mg twice a day for at least 48 hours showed a reduction in inpatient mortality and progression of pulmonary symptoms (such as shortness of breath or cough) compared to published reports of COVID-19 patients in 2020.2
What should you be aware of when taking cetirizine?
Cetirizine can be more sedating than fexofenadine and loratadine, so you may feel more drowsiness or fatigue, especially if you are taking other potentially sedating medications. Some side effects of cetirizine may include headaches, dry mouth, and dizziness.
References:
Active Clinical Trials: Long COVID, antihistamines | Card Results | ClinicalTrials.gov
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