Calm a Cytokine Storm During COVID
DISCLAIMER: CONSULT WITH A DOCTOR BEFORE DECIDING ON A TREATMENT PLAN FOR ANY DISEASE OR INJURY.
Scientists have been studying cytokine storms for a while in relation to the way that they lead influenza patients into dangerous territory just as the most active phase of infection gets under control. If you are doing at-home COVID treatment or if you are treating any type of major infection that can involve a cytokine storm, you need to hold off on giving the patient immunomodulating or immunosuppressive treatments until the acute phase of the illness ends. The acute phase of illness may vary depending on the type of infection, but with respiratory illnesses like COVID-19, the onset of coughing, approximately 2 to 3 days after the first sign of illness signals that it’s time to start giving the patient Vitamin B3 (Nicotinic Acid) supplementation.
NOTE: Reactive Oxygen Species medicines could theoretically worsen the disease progression after the first 2 to 3 days of the illness. Read more HERE.
Phase 1 COVID Treatment At Home
Phase 1 is the acute phase of the illness that is generally less severe. It lasts approximately 2 to 3 days. During this time, it can be valuable to administer anti-viral medications such as Reactive Oxygen Species Medicines that can help the immune system attack the virus.
Phase 2 COVID Cytokine Storm Treatment At Home
When coughing begins, it’s time to switch to anti-cytokine medicines such as Carica papaya or Selank. There are a number of anti-cytokine medicines listed below. Don’t double up on these anti-cytokine medicines unless you’ve scientifically verified that they will NOT cancel each other out.
When coughing begins, administer daily doses of vitamin B3 (also known as Nicotinic Acid) at 500 mg twice per day to protect the lung tissues and stimulate blood flow.
Cytokine Storm Treatments That Work
In the case that a person still has a primary infection, but is also experiencing a cytokine storm, they may pursue therapies that specifically work to repress the action of cytokines such as TNF-alpha or IFN-gamma. This will help reduce the intensity of the cytokine storm while also allowing other cytokines and immune cells to do their jobs in fighting the infection. Some of the medicines listed below, such as luteolin, also have an antiviral effect, making them a particularly good choice for people struggling with both a primary infection and cytokine storm. For people who are certain that they have recovered from COVID-19, the goal is to calm the immune system in a very general way (though specifically targeting the cytokines noted in the above section is recommended).
Some of the most valuable treatments for calming cytokine storm include:
- Fumaric acid – This is a popular psoriasis treatment, is known for its ability to repress the production of TNF-alpha, as well as interleukin-12 and interleukin-23, two other inflammatory agents. Fumaric acid can also help reduce the amount of glutathione in immune cells, which then spurs the creation of heme-oxygenase 1 (HO-1), an anti-inflammatory protein. 2
- Curcumin (intravenous) – This turmeric-derived compound stops the production pathways of especially damaging inflammatory cytokines involved in cytokine storms. It specifically works to inhibit the production of TNF-alpha, IL-12, and other inflammatory proteins. Curcumin also modulates the production of IL-10, an anti-inflammatory protein that decreases the production of TNF-alpha and other inflammatory cytokines. It has been used in the treatment of COVID-19 and cytokine storms in patients in Iran.
- Luteolin – Stops the production pathways of especially damaging inflammatory cytokines involved in cytokine storms. This flavonoid can prevent the production of TNF-alpha, IFN-gamma, and other inflammatory agents. We talk about luteolin later in this book as a treatment for the COVID-19 infection itself, and it can also work to defeat cytokine storms, making it a particularly valuable treatment for people struggling with both issues.
- Piperine – A flavonoid that stops the production pathways of especially damaging inflammatory cytokines involved in cytokine storms. It is an extract that comes from black peppercorns. This is another effective remedy for not only cytokine storms, but also for COVID-19 itself. Piperine can bind with the spike glycoprotein surrounding the COVID-19 virus, inhibiting its ability to bind to other healthy cells in the body, and it can also prevent the production of TNF-alpha and other inflammatory cytokines.
- Resveratrol – This polyphenolic compound stops the production pathways of especially damaging inflammatory cytokines involved in cytokine storms. Resveratrol works to inhibit the production of both TNF-alpha and IFN-gamma, the two most problematic cytokines in cytokine storms.
- Eugenol – This aromatic oil extracted from cloves has an effect on reducing the production of TNF-alpha and IL-6 in particular. It is an antioxidant, antiviral, and anti-inflammatory agent and can be used safely in many cases as an adjuvant therapy to treat both COVID-19 as well as any excess inflammation that may occur.
- Gingerol – This is a naturally occurring ketone that is present in fresh ginger and in some other fresh rhizomes in the ginger family. It has the ability to inhibit the production of certain cytokines, including TNF-alpha and IL-6. When used with other antiviral components or other parts of a cytokine storm treatment protocol, it can be a helpful therapeutic addition.
- Melatonin – Though popularly marketed as a sleep aid, melatonin also has other valuable anti-inflammatory properties that can help stop a cytokine storm. This compound can inhibit the pathways leading to the production of both TNF-alpha and IFN-gamma, as well as the pathways leading to the production of certain other problematic inflammatory cytokines. Melatonin may be taken in supplement form, and/or it may be obtained from certain foods, including celery, barley, turmeric, black pepper, fennel, coriander, flaxseeds, and more.
- Quercetin – Quercetin is an anti-inflammatory flavonoid that has been proven to have positive effects in the treatment of various diseases, such as rheumatic disease, cardiovascular disease, and others. Quercetin works to inhibit the production of TNF-a, and IL-6, and increases the production of the anti-inflammatory cytokine IL-27. However, it has also been found to increase levels of IFN-gamma, which in the case of a severe cytokine storm, may not be positive. Nonetheless, quercetin has valuable applications in the treatment of COVID-19 and cytokine storms.
- Nicotine – Nicotine is a naturally occurring flavonoid not only found in tobacco (although this is the most prolific source of nicotine), it can also be found in smaller quantities in some vegetables, including tomatoes, potatoes, eggplants, and peppers. It successfully can lower the production of both IFN-gamma and TNF-alpha (in addition to some other pro-inflammatory cytokines) and is currently approved as a clinical treatment option for some other inflammatory issues such as ulcerative colitis. (NOTE: Nicotine refers to a naturally occurring flavonoid. This does not mean that smoking is good. Pure tobacco used for medicinal purposes only and plants that naturally contain nicotine, or standardized nicotine extracts, are what we are referring to here)
- Nicotinic Acid, also known as Niacinamide or Vitamin B3, is a vital vitamin that particularly works to protect the lungs. As soon as coughing begins, infection-level doses of vitamin B3 should be administered. Nicotinic acid is chemically the same as nicotine except that it has been oxidized with nitric oxide. The use of vitamin B3 is a better, healthier option than the use of nicotine for the treatment of cytokine storm.
- Tuftsin – Tuftsin is a tetrapeptide that is naturally produced in the human body. It is a natural immunomodulator that is antiviral, antifungal, antibacterial, anti-tumor, and also an anticoagulant (it prevents the development of blood clots). It improves communication among the various elements of the immune system to upregulate or downregulate the immune system response as needed. Scientists have shown that this peptide (Thr-Lys-Pro-Arg) not only can be used to increase red blood cell production in bone marrow, but it also regulates dopamine, serotonin, and norepinephrine while preventing the degradation and death of nerve tissues. As such, it can help relieve withdrawal symptoms in situations involving addiction. Tuftsin has been used to prevent cerebral hemorrhage and it can help heal gastric ulcers too. It can be used to increase the effectiveness of an anti-Candida albicans protocol. But most importantly for our discussion here, Tuftsin has special properties that make it an excellent candidate for use as a remedy for cytokine storm. There are Tuftsin receptors on endothelial cells, and in addition to its general immunomodulator effects on the body, Tuftsin also increases blood pressure. 14
- Selank – Selank is a synthetic analogue of Tuftsin that can be purchased online.
- Carica Papaya Leaf Extract – Carica papaya has been used for years to treat dengue infection, a tropical disease that is also known as “break bone fever” because it can cause extreme bone pain in individuals who develop an active infection. But the most dangerous type of disease progression in patients infected with dengue happens when a cytokine storm leads to the hemorrhagic version of the disease. This hemorrhagic presentation of dengue is comparable to the hemorrhagic presentation of Ebola, but it is related to the vasoplegic effects that occur in certain COVID-19 infections. These vasoplegic effects occur because of a cytokine storm. About 72.5% of COVID patients who were hospitalized developed thrombocytopenia after admission. Carica papaya is extremely effective at treating thrombocytopenia and other symptoms of cytokine storm now matter what the underlying cause.
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- Morphine/ Codeine / Laudanum– These two opioid alkaloids require further research before they can be considered as treatments for COVID-19 cytokine storms in a clinical setting, but so far studies have shown that they may be valuable immunosuppressives. Morphine in particular, when administered at the correct time, can reduce levels of both TNF-alpha and IFN-gamma. However, caution must be used because some people can experience respiratory depression when using morphine, which can be detrimental in cases where the person is already struggling with severe respiratory symptoms. 4
Hydroxychloroquine and chloroquine, two frequently and successfully used medications for the treatment of COVID-19, not only have an antiviral effect, but they also help suppress the overproduction of TNF-alpha, IFN-gamma, IL-6, and other inflammatory cytokines. Though these are both pharmaceuticals, they have been used safely for years in the treatment of malaria. In some particularly serious COVID-19 cases, these two medications can be highly effective. They both fight the COVID-19 infection as well as keep the cytokine storm from getting out of control. 4
Anakinra, sometimes sold under the brand name Kineret, is a medication that is currently approved in the US for the treatment of rheumatoid arthritis. It is an interleukin antagonist. According to initial studies into this medication, the risks with treatment are extremely low, and for patients struggling with even the most severe cytokine storms it can produce miraculous results. It has been used in the treatment of HLH (hemophagocytic lymphohistiocytosis) in infants with surprisingly successful results. 5
Anakinra helps selectively inhibit certain cytokines from being produced (specifically, it targets interleukin-1). It is administered as a subcutaneous injection given once a day. The first injection is given at a doctor’s office, but following the first visit, some people may be allowed to perform their injections at home with the help of a caregiver. 5
The authors of this book would advise using anakinra in combination with other healing therapies in this book to holistically treat a COVID-19 infection successfully. Because anakinra does lower the body’s ability to fight infection, it’s important that you’re treating the COVID infection in other ways too, if possible. Talk to your doctor or health specialist to determine a protocol that will work best for your situation.5
NOTE: Beta-glucans help encourage the production of TNF-alpha and IFN-gamma rather than discouraging their production. In situations where a person’s immune response is low, this is a good thing. But with a cytokine storm, an overactive immune response, this medicine would be counterproductive. For individuals with COVID-19 infections who are not experiencing a cytokine storm, beta-glucans have a positive effect on healing the respiratory system. Individuals who have both COVID-19 and are also having a cytokine storm, or people who are trying to calm a cytokine storm in general, should avoid beta-glucans. 3
 Tweedell, Rebecca (2020). How to calm the cytokine storm in COVID-19 and beyond. Retrieved October 12, 2021 from: https://blogs.stjude.org/progress/cytokine-storm-calmed-through-inflammatory-disease-drugs-2.html
 Balak, M.W. Deepak. (2015). Fumaric acid esters in the management of psoriasis. Retrieved May 21, 2021 from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5683116/
 Jockers, D. (2018). How Beta Glucans Boost Immunity & Fight Cancer. Retrieved May 25, 2018 from https://thetruthaboutcancer.com/beta-glucans-immunity-fight-cancer/
 Kalpana, V. Lakshmi; Peter, Angela E.; Rao, B. Ganga; Sandeep, B.V. (2021). Calming the Storm: Natural Immunosuppressants as Adjuvants to Target the Cytokine Storm in COVID-19. Retrieved October 12, 2021 from: https://www.frontiersin.org/articles/10.3389/fphar.2020.583777/full
 University of Alabama at Birmingham (2019). Here’s a playbook for stopping deadly cytokine storm syndrome. Retrieved October 13, 2021 from: https://www.newswise.com/articles/here-s-a-playbook-for-stopping-deadly-cytokine-storm-syndrome
 Siebert, A. et al. (2014). Tuftsin-Properties and Analogs. Retrieved October 27, 2021 from file:///Users/jennifershipp/Downloads/tuftsin-properties-and-analogs_15672.pdf
 Norahmad, N. A. et al. (2019). Effect of freeze-dried Carica papaya leaf juice on inflammatory cytokines production during dengue virus infection in AG129 mice. Retrieved October 27, 2021 from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371484/
 Wikipedia (2021). Selank. Retrieved October 27, 2021 from https://en.wikipedia.org/wiki/Selank
 McW Healthcare (2021). Immunity: The Double Edged Sword in SARS CoV-2Retrieved October 27, 2021 from https://www.mcwhealthcare.com/immunity-the-double-edged-sword-in-sars-cov-2/
 ClinicalTrials.gov (2021). Improvement of the Nutritional Status Regarding Nicotinamide (Vitamin B3) and the Disease Course of COVID-19 (CoVit-2). Retrieved October 17, 2021 from https://clinicaltrials.gov/ct2/show/NCT04751604