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COVID HEART: HIDDEN DANGER IN ATHLETES

October 06, 2020 - Admin
category: Energy, Fat Burning, Health, Muscle Growth, Performance, Recovery, Sleep, Strength, Thermo Heat, Thermo Heat Multi, Thermo Heat Nighttime, Thermo Heat Protein, Thermo Heat™ Weight Loss Revolution

By Steve Blechman

 

This week, the Centers for Disease Control and Prevention (CDC) revised its coronavirus guidelines stating that the virus is spread through close contact with a person (respiratory droplets) who has COVID-19 then by airborne transmission. However, the CDC still recognizes that there is evidence that transmission of tiny airborne particles (aerosols) can occur greater than 6 feet away in people who are exercising heavily, especially indoors, and without proper ventilation or wearing a mask.

New England Patriots star quarterback Cam Newton tested positive for COVID-19 this past weekend. After three weeks of the start of the NFL season more players, coaches and staff members have tested positive for COVID-19. Without social distancing between themselves and the public, it’s no surprise!

It was reported on September 11, 2020 in Science News that, “More than two dozen male and female competitive athletes underwent magnetic resonance imaging of their hearts in the weeks to months after a positive test for SARS-CoV-2, the virus that causes COVID-19. The images indicated swelling in the heart muscle and possible injury to cells in four of the athletes, or 15 percent, researchers report online September 11 in JAMA Cardiology. That could mean the athletes had myocarditis, an inflammation of the heart muscle most frequently caused by viral infections.” Myocarditis has caused heart failure and is a leading cause of death in young, otherwise healthy adults.

Science News further reported that, “It will take more research to confirm the study’s findings and understand what they could mean for these young hearts. For now, the results suggest the heart may be at risk of injury, and serve as a reminder that after having COVID-19 – even with mild or no symptoms – young people need to pay close attention to how they are feeling when they return to exercise, says Dr. Saurabh Rajpal, an assistant professor of cardiology at Ohio State University and lead researcher of the JAMA Cardiology study. “If they have symptoms like chest pain, shortness of breath or an abnormal heartbeat,” he says, “they should see a doctor.”

In another recent study in JAMA Cardiology, researchers did magnetic resonance imaging (MRI) of the hearts of 100 middle-aged adults recovering with COVID-19. Seventy-eight percent had “cardiac involvement” and inflammation of the heart! This is very concerning. The researchers concluded that, “these findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.”

The cytokine storm is the major cause of death from the coronavirus! The cytokine storm is a severely dangerous hyperimmune reaction to infection of the coronavirus in the lungs, in which the immune system overproduces inflammatory cytokines, which can damage lungs and cause inflammation of the air sacs of the lung, which can inhibit oxygen in the body – causing pneumonia, respiratory failure and the requirement of a ventilator. Recent research has shown that the cytokine storm can also cause inflammation and cell damage to the heart, liver, brain, kidneys, intestines, as well as cause abnormal blood clots, which are causing lower body amputations and sudden cardiac thrombosis and death.

In those people infected with the COVID-19 virus, the coronavirus particles enter your body through your nose, mouth or eyes, into your lungs. The immune system recognizes the virus and sends immune-signaling molecules called cytokines such as interleukin-6 (IL-6) and tumor necrosis factor (TNF). Normally these cytokines play a beneficial role by activating our innate immune response and certain white blood cells called macrophages, neutrophils and natural killer cells that destroy and kill certain dangerous pathogens, bacteria and viruses. These white blood cells are like “killer, phagocytic Pac-Men” that release reactive oxygen species (ROS) free radicals and kill these bacteria and viruses. At the same time, these ROS free radical species damage normal tissues and cause inflammation and cell death. So these white blood cells in fact are a two-edged sword – they kill dangerous viruses and bacteria or they can go haywire, causing severe inflammation, cell damage and organ failure!

The anti-inflammatory drugs approved for treating rheumatoid arthritis such as tocilizumab (Actemra) has great potential in treating COVID-19 patients with the deadly cytokine storm. Also, the inexpensive generic steroid drug dexamethasone reduces death rates by one-third with the most severe cases of infections. It is a major breakthrough treatment. These anti-inflammatory drugs reduce inflammation and tame down the cytokine storm and hyperactive immune response in some very ill patients. These drugs also have many side effects, but the benefits far outweigh the risks and can potentially save many lives!

A randomized, crossover study published January 7, 2019 in the Journal of the American College of Nutrition found a short-term Mediterranean diet can improve endurance exercise performance in as little as four days in men and women. The Mediterranean diet, an anti-inflammatory diet, has great potential to naturally help tame down the uncontrolled hyperimmune response, which causes the potentially deadly cytokine storm and severe inflammation. The Mediterranean diet is the healthiest diet based on the latest scientific research. A healthy diet and lifestyle changes, such as following the anti-inflammatory Mediterranean diet along with exercise, has been shown to lower the risk of obesity, metabolic syndrome and high-risk ailments such as cardiovascular disease and diabetes. For the past two years, U.S. News & World Report ranked the Mediterranean diet as the best overall diet for healthy eating, tied with the Dash Diet. The Mediterranean diet was also ranked #1 for the easiest diet to follow; best diet for diabetes; best heart-healthy diet, and best plant-based diet too.

The Mediterranean diet is high in fish containing omega-3 fatty acids, in addition to antioxidant-rich vegetables, red wine and berries rich in polyphenols, beans, lentils, nuts, legumes and extra-virgin-olive oil that are rich in healthy monounsaturated polyunsaturated fats and low in saturated fats. A recent study by Harvard researchers and reported by the American Heart Association (March 5, 2020) and published in the Journal of the American College of Cardiology (March 2020) found that as little as half a tablespoon of olive oil a day was linked to significant decrease in cardiovascular disease. Research has shown that omega-3 fatty acids (primarily EPA and DHA) found in fatty fish such as salmon have potent anti-inflammatory properties and reduced inflammation and protect against heart disease. It was reported recently in The Wall Street Journal (June 3, 2020) that, “Amarin Corporation plans to test its fish oil-derived drug Vascepa, whicih can prevent and treat COVID-19 infection and reduce the risk of cardiovascular problems in patients who sustain heart damage during their illness.” This story added: “Amarin says Vascepa may help prevent or treat inflammation.”

Omega-3 fatty acids (EPA and DHA) both lower inflammation. Some research has shown that DHA is a more anti-inflammatory than EPA. These omega-3 fatty acids can lower inflammatory compounds called leukotrienes in the body. These leukotrienes are produced naturally from arachidonic acid, a polyunsaturated fat found in animal fats present in meat, poultry, eggs and cheese. High arachidonic acid levels in the body can increase inflammation and the inflammatory cascade, which can lead to the cytokine storm in susceptible individuals. That’s why it’s very important to limit animal fats and arachidonic acid in the anti-inflammatory Mediterranean diet and eat more omega-3 rich fish such as salmon.

Research has shown that inflammation is a major risk factor for cardiovascular disease. Research has also shown that the traditional Mediterranean diet can reduce inflammation and improve cardiovascular health (Nutrients, August 9, 2020). Sixteen years ago the ATTICA Study (J Am Coll Cardiol, July 2004) found that the Mediterranean diet was associated with a 20 percent lower c-reactive protein (CRP) and 17 perdent lower levels of interleukin-6 (IL-6). CRP and IL-6 are elevated in systemic inflammation in the body. This was an observational study and demonstrated an association but not proof of cause and effect like a randomized, double-blind clinical trial; also, a similar study a year later called the Nurses’ Cohort in the USA (Am J Clin Nut, July 2005) was associated to a 24 percent lower c-reactive protein and 16 percent lower levels of interleukin-6 (IL-6). These very well-conducted observational studies were later confirmed by a randomized clinical trial (PREDIMED pilot study). The Mediterranean diet supplemented with extra-virgin olive oil for three months that human adults followed reduced c-reactive protein. The Mediterranean diet, as I mentioned, was supplemented with extra-virgin oil containing monounsaturated fats and polyphenols and lowered low-grade inflammation implicated in the mechanism leading to atherosclerotic disease (Nutr Metab, September 2014). The PREDIMED trial later involving 1,139 high-risk cardiovascular adults further confirmed a dose-dependent anti-inflammatory of the Mediterranean diet rich in polyphenols based on measuring inflammatory biomarkers such as c-reactive protein and interleukin-6 (Br J Clin Pharmaca, January 2017). A later study (CANTOS trial) found that a monoclonal antibody that reduces c-reactive protein, interleukin-6 and inflammation, further confirmed the inflammatory hypothesis in atherosclerosis and cardiovascular disease without lowering blood lipids (N Engel J Med, Jan. 1999, Endocrinol Diabet Nutr, Nov. 2017). The Mediterranean diet containing extra-virgin olive oil, fruits, and red wine is rich in polyphenols with potent anti-inflammatory properties.

Recently, the Cleveland Clinic published a scientific review (June 2, 2020, Cleveland Clinic Journal of Medicine) entitled, What is the role of supplementation with ascorbic acid, zinc, vitamin D, or N-acetylcysteine for prevention or treatment of COVID-19? The review mentioned that zinc, vitamin D, and N-acetylcysteine (NAC) can lower pro-inflammatory cytokines such as interleukin-6 (IL-6), interleukin-1 (IL-1) and tumor necrosis factor (TNF). The authors outline, “the biological plausibility, applicable clinical data and potential role of each of these agents.” The Cleveland Clinic investigators continued to say that, “several agents intended to supplement dietary intake or indigenous molecules may have a theoretical role in preventing or treating COVID-19.” Based on their scientific review, the authors further acknowledge that “ascorbic acid, zinc, vitamin D, and N-acetylcysteine have biologic plausibility for prevention and treatment of COVID-19 and are candidates for clinical trials evaluating patients with these indications.”

In conclusion, as we all know the coronavirus is a very infectious disease. We know that the virus can spread through close contact with an infected person. We also know that airborne transmission can occur greater than 6 feet away in people that are exercising heavily, especially indoors at your local gym. Don’t stop working out at your local gym! Exercise is essential for good health! Don’t be foolish. Protect your heart, lungs and body by wearing a mask indoors when exercising. Better to be safe than sorry! Also, follow a healthy nutritional diet and lifestyle such as the anti-inflammatory Mediterranean diet, as mentioned in my previous articles. Eating healthy, improving our metabolic health and exercising more can help control our weight, lower inflammation and improve our metabolic health and fitness.

©Published by Advanced Research Media, Inc. 2020

©Reprinted with permission from Advanced Research Media, Inc.

 

References:

  1. College athletes show signs of possible heart injury after COVID-19 by Aimee Cunningham. September 11, 2020. Science News https://www.sciencenews.org/article/covid19-coronavirus-heart-injury-college-athletes-sports
  1. Rajpal S, Tong MS, Borchers J, et al. Cardiovascular Magnetic Resonance Findings in Competitive Athletes Recovering From COVID-19 Infection. JAMA Cardiol.Published online September 11, 2020. doi:10.1001/jamacardio.2020.4916 
  1. Puntmann VO, Carerj ML, Wieters I, et al. Outcomes of Cardiovascular Magnetic Resonance Imaging in Patients Recently Recovered From Coronavirus Disease 2019 (COVID-19). JAMA Cardiol.Published online July 27, 2020. doi:10.1001/jamacardio.2020.3557
  1. Baker ME, DeCesare KN, Johnson A, Kress KS, Inman CL, Weiss EP. Short-Term Mediterranean Diet Improves Endurance Exercise Performance: A Randomized-Sequence Crossover Trial. J Am Coll Nutr. 2019 Sep-Oct;38(7):597-605. doi: 10.1080/07315724.2019.1568322. Epub 2019 Feb 13. PMID: 30758261.
  1. Quercetin and Vitamin C: An Experimental, Synergistic Therapy for the Prevention and Treatment of SARS-CoV-2 Related Disease (Covid-19.) Frontiers in Immunology. Colunga Biancatelli Ruben Manuel Luciano, Berrill Max, Catravas John D, et al. June 19, 2020. https://www.frontiersin.org/articles/10.3389/fimmu.2020.01451/full
  1. Wu W, Li R, Li X, et al. Quercetin as an Antiviral Agent Inhibits Influenza A Virus (IAV) Entry. Viruses. 2015;8(1):6. Published 2015 Dec 25. doi:10.3390/v8010006  
  1. Cheng RZ. Can early and high intravenous dose of vitamin C prevent and treat coronavirus disease 2019 (COVID-19)?. Med Drug Discov. 2020;5:100028. doi:10.1016/j.medidd.2020.100028 
  1. Boretti A, Banik BK. Intravenous Vitamin C for reduction of cytokines storm in Acute Respiratory Distress Syndrome [published online ahead of print, 2020 Apr 21]. PharmaNutrition. 2020;12:100190. doi:10.1016/j.phanu.2020.100190  
  1. Carr AC. A new clinical trial to test high-dose vitamin C in patients with COVID-19. Crit Care. 2020;24(1):133. Published 2020 Apr 7. doi:10.1186/s13054-020-02851-4 
  1. Mani JS, Johnson JB, Steel JC, et al. Natural product-derived phytochemicals as potential agents against coronaviruses: A review. Virus Res. 2020;284:197989. doi:10.1016/j.virusres.2020.197989  
  1. Jasso-Miranda C, Herrera-Camacho I, Flores-Mendoza LK, et al. Antiviral and immunomodulatory effects of polyphenols on macrophages infected with dengue virus serotypes 2 and 3 enhanced or not with antibodies. Infect Drug Resist. 2019;12:1833-1852. Published 2019 Jul 1. doi:10.2147/IDR.S210890 
  1. Li Y, Yao J, Han C, et al. Quercetin, Inflammation and Immunity. Nutrients. 2016;8(3):167. Published 2016 Mar 15. doi:10.3390/nu8030167  
  1. Hemilä H, Chalker E. Vitamin C as a Possible Therapy for COVID-19. Infect Chemother. 2020;52(2):222-223. doi:10.3947/ic.2020.52.2.222  
  1. Glinsky GV. Tripartite Combination of Candidate Pandemic Mitigation Agents: Vitamin D, Quercetin, and Estradiol Manifest Properties of Medicinal Agents for Targeted Mitigation of the COVID-19 Pandemic Defined by Genomics-Guided Tracing of SARS-CoV-2 Targets in Human Cells. Biomedicines. 2020;8(5):129. Published 2020 May 21. doi:10.3390/biomedicines8050129
  1. Liu F, Zhu Y, Zhang J, et alIntravenous high-dose vitamin C for the treatment of severe COVID-19: study protocol for a multicentre randomised controlled trialBMJ Open 2020;10:e039519. doi: 10.1136/bmjopen-2020-039519
  1. Boretti A, Banik BK. Intravenous Vitamin C for reduction of cytokines storm in Acute Respiratory Distress Syndrome [published online ahead of print, 2020 Apr 21]. PharmaNutrition. 2020;12:100190. doi:10.1016/j.phanu.2020.100190 
  1. Cheng RZ. Can early and high intravenous dose of vitamin C prevent and treat coronavirus disease 2019 (COVID-19)? Med Drug Discov. 2020;5:100028. doi:10.1016/j.medidd.2020.10002 
  1. Song Y, Zhang M, Yin L, et al. COVID-19 Treatment: Close to a Cure? - A Rapid Review of Pharmacotherapies for the Novel Coronavirus [published online ahead of print, 2020 Jul 4]. Int J Antimicrob Agents. 2020;106080. doi:10.1016/j.ijantimicag.2020.106080 
  1. Ngwa W, Kumar R, Thompson D, et al. Potential of Flavonoid-Inspired Phytomedicines against COVID-19. Molecules. 2020;25(11):2707. Published 2020 Jun 11. doi:10.3390/molecules25112707
  1. Wong G, He S, Siragam V, et al. Antiviral activity of quercetin-3-β-O-D-glucoside against Zika virus infection. Virol Sin. 2017;32(6):545-547. doi:10.1007/s12250-017-4057-9  
  1. Guo Y, Zhang P, Liu Y, Zha L, Ling W, Guo H. A dose-response evaluation of purified anthocyanins on inflammatory and oxidative biomarkers and metabolic risk factors in healthy young adults: A randomized controlled trial. Nutrition. 2020;74:110745. doi:10.1016/j.nut.2020.110745  
  1. Strodel, Birgit & Olubiyi, Olujide & Olagunju, Maryam & Keutmann, Monika & Loschwitz, Jennifer. (2020). High Throughput Virtual Screening to Discover Inhibitors of the Main Protease of the Coronavirus SARS-CoV-2. 10.20944/preprints202004.0161.v1. 
  1. Coppola M, Mondola R. Phytotherapeutics and SARS-CoV-2 infection: Potential role of bioflavonoids [published online ahead of print, 2020 Apr 22]. Med Hypotheses. 2020;140:109766. doi:10.1016/j.mehy.2020.109766 
  1. What is the role of supplementation with ascorbic acid, zinc, vitamin D, or N-acetylcysteine fo r prevention or treatment of COVID-19? Seth R. Bauer, Aanchal Kapoor, Mary Rath, Suma A. Thomas, Cleveland Clinic Journal of Medicine Jun 2020, DOI: 10.3949/ccjm.87a.ccc046  
  1. Hemilä H, Chalker E. Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev 2013; 2013(1). doi:10.1002/14651858.CD000980.pub4   
  1. Carr AC. Vitamin C administration in the critically ill: a summary of recent meta-analyses. Crit Care 2019; 23(1):265. doi:10.1186/s13054-019-2538-y  
  1. Velthuis AJW, van den Worm SHE, Sims AC, Baric RS, Snijder EJ, van Hemert MJ. Zn2+ inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture. PLoS Pathog 2010; 6(11). doi:10.1371/journal.ppat.1001176
  1. Singh M, Das RR. Zinc for the common cold. Cochrane Database Syst Rev 2013; 2013(6):CD001364. doi:10.1002/14651858.CD001364.pub4 
  1. Grant WB, Lahore H, McDonnell SL, et al. Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients 2020; 12(4):988. doi:10.3390/nu12040988  
  1. Martineau AR, Jolliffe DA, Hooper RL, et al. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ 2017; 356. doi:10.1136/bmj.i658 
  1. Sadowska AM, Manuel-y-Keenoy B, De Backer WA. Antioxidant and anti-inflammatory efficacy of NAC in the treatment of COPD: discordant in vitro and in vivo dose-effects: a review. Pulm Pharmacol Ther 2007; 20(1):9-22. doi:10.1016/j.pupt.2005.12.00 
  1. Coronavirus Pandemic: Diet and Nutrition Battling the Deadly Cytokine Storm - The Latest Research! Steve Blechman. Advanced Molecular Labs. April 24, 2020 https://advancedmolecularlabs.com/blogs/news/coronavirus-pandemic-diet-and-nutrition-battling-the-deadly-cytokine-storm-the-latest-research
  1. Kate J Claycombe-Larson, Travis Alvine, Dayong Wu, Nishan S Kalupahana, Naima Moustaid-Moussa, James N Roemmich, Nutrients and Immunometabolism: Role of Macrophage NLRP3, The Journal of Nutrition, nxaa085, https://doi.org/10.1093/jn/nxaa085
  1. Calder, P.C.; Carr, A.C.; Gombart, A.F.; Eggersdorfer, M. Optimal Nutritional Status for a Well-Functioning Immune System Is an Important Factor to Protect against Viral Infections. Nutrients 2020, 12, 1181.  
  1. Efficacy of glutathione therapy in relieving dyspnea associated with COVID-19 pneumonia: A report of 2 cases. Author links open overlay panel. Richard I.Horowitz. Phyllis R.Freeman. James Bruzzesec. Respiratory Medicine Case Reports. Volume 30, 2020, 101063. https://doi.org/10.1016/j.rmcr.2020.101063
  1. University of Surrey. Link identified between dietary selenium and outcome of COVID-19 disease. ScienceDaily. ScienceDaily, 29 April 2020. www.sciencedaily.com/releases/2020/04/200429105907.htm  
  1. Margaret P Rayman, Ramy Saad, Kate Bennett, Ethan Will Taylor, Jinsong Zhang. Association between regional selenium status and reported outcome of COVID-19 cases in China. The American Journal of Clinical Nutrition, 2020; DOI: 10.1093/ajcn/nqaa095  
  1. Ilie PC, Stefanescu S, Smith L. The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality [published online ahead of print, 2020 May 6]. Aging Clin Exp Res. 2020;1‐4. doi:10.1007/s40520-020-01570-8  
  1. Gruber-Bzura BM. Vitamin D and Influenza-Prevention or Therapy? Int J Mol Sci. 2018;19(8):2419. Published 2018 Aug 16. doi:10.3390/ijms19082419   
  1. Ratih Wirapuspita Wisnuwardani, Stefaan De Henauw, Marika Ferrari, Maria Forsner, Frédéric Gottrand, Inge Huybrechts, Antonios G Kafatos, Mathilde Kersting, Viktoria Knaze, Yannis Manios, Ascensión Marcos, Dénes Molnár, Joseph A Rothwell, Azahara Iris Rupérez, Augustin Scalbert, Kurt Widhalm, Luis A Moreno, Nathalie Michels, Total Polyphenol Intake Is Inversely Associated with a Pro/Anti-Inflammatory Biomarker Ratio in European Adolescents of the HELENA Study, The Journal of Nutrition, nxaa064, https://doi.org/10.1093/jn/nxaa064
  1. Bao B, Prasad AS, Beck FW, et al. Zinc decreases C-reactive protein, lipid peroxidation, and inflammatory cytokines in elderly subjects: a potential implication of zinc as an atheroprotective agent. Am J Clin Nutr. 2010;91(6):1634‐1641. doi:10.3945/ajcn.2009.28836   
  1. Silberstein M. Vitamin D: A simpler alternative to tocilizumab for trial in COVID-19? [published online ahead of print, 2020 Apr 23]. Med Hypotheses. 2020;140:109767. doi:10.1016/j.mehy.2020.109767 
  1. Aziz, M., Fatima, R. and Assaly, R. (2020), Elevated Interleukin‐6 and Severe COVID‐19: A Meta‐Analysis. J Med Virol. Accepted Author Manuscript. doi:10.1002/jmv.25948  
  1. Covid-19 in Immune-Mediated Inflammatory Diseases - Case Series from New York. April 29, 2020. DOI: 10.1056/NEJMc2009567.
  1. Giovannini C, Filesi C, D'Archivio M, Scazzocchio B, Santangelo C, Masella R. Polifenoli e difese antiossidanti endogene: effetti sul glutatione e sugli enzimi ad esso correlati [Polyphenols and endogenous antioxidant defences: effects on glutathione and glutathione related enzymes]. Ann Ist Super Sanita. 2006;42(3):336‐347. 
  1. Margaret P Rayman, Ramy Saad, Kate Bennett, Ethan Will Taylor, Jinsong Zhang. Association between regional selenium status and reported outcome of COVID-19 cases in China. The American Journal of Clinical Nutrition, 2020; DOI: 10.1093/ajcn/nqaa095 
  1. University of Surrey. Link identified between dietary selenium and outcome of COVID-19 disease. ScienceDaily. ScienceDaily, 29 April 2020. www.sciencedaily.com/releases/2020/04/200429105907.htm 
  1. Jinsong Zhang, Ethan Will Taylor, Kate Bennett, Ramy Saad, Margaret P Rayman, Association between regional selenium status and reported outcome of COVID-19 cases in China, The American Journal of Clinical Nutrition, nqaa095, https://doi.org/10.1093/ajcn/nqaa095
  1. The Possible Role of Vitamin D in Suppressing Cytokine Storm and Associated Mortality in COVID-19 Patients. Ali Daneshkhah, Vasundhara Agrawal, Adam Eshein, Hariharan Subramanian, Hemant Kumar Roy, Vadim Backman. medRxiv 2020.04.08.20058578; doi: https://doi.org/10.1101/2020.04.08.2005857
  1. Thailand Medical News. BREAKING! COVID-19 Research: Russian Study Indicates That Glutathione Deficiency Affects COVID-19 Susceptibility, NAC Supplements Helps. Apr 26, 2020 https://www.thailandmedical.news/news/breaking-covid-19-research-russian-study-indicates-that-glutathione-deficiency-affects-covid-19-susceptibility,-nac-supplements-helps
  1. Endogenous deficiency of glutathione as the most likely cause of serious manifestations and death in patients with the novel coronavirus infection (COVID-19): a hypothesis based on literature data and own observations. DO - 10.21626/vestnik. Polonikov, Alexey. 2020/04/25. ResearchGate  
  1. De Flora S, Grassi C, Carati L. Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment. Eur Respir J. 1997;10(7):1535‐1541. doi:10.1183/09031936.97.10071535
  1. N-acetylcysteine: A rapid review of the evidence for effectiveness in treating COVID-19 by Dr Oliver Van Hecke, Dr Joseph Lee. CEBM. April 14, 2020 https://www.cebm.net/covid-19/n-acetylcysteine-a-rapid-review-of-the-evidence-for-effectiveness-in-treating-covid-19/
  1. De Rosa SC, Zaretsky MD, Dubs JG, et al. N-acetylcysteine replenishes glutathione in HIV infection. Eur J Clin Invest. 2000;30(10):915‐929. doi:10.1046/j.1365-2362.2000.00736.x  
  1. Shu Y, Wu M, Yang S, Wang Y, Li H. Association of dietary selenium intake with telomere length in middle-aged and older adults [published online ahead of print, 2020 Jan 31]. Clin Nutr. 2020;S0261-5614(20)30037-6. doi:10.1016/j.clnu.2020.01.014  
  1. McCarty MF, DiNicolantonio JJ. Nutraceuticals have potential for boosting the type 1 interferon response to RNA viruses including influenza and coronavirus [published online ahead of print, 2020 Feb 12]. Prog Cardiovasc Dis. 2020;. doi:10.1016/j.pcad.2020.02.007 
  1. Ungheri D, Pisani C, Sanson G, et al. Protective effect of n-acetylcysteine in a model of influenza infection in mice. Int J Immunopathol Pharmacol. 2000;13(3):123‐128.  
  1. Prasad AS, Beck FW, Bao B, et al. Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress. Am J Clin Nutr. 2007;85(3):837‐844. doi:10.1093/ajcn/85.3.837
  1. Glutathione Fine-Tunes the Innate Immune Response toward Antiviral Pathways in a Macrophage Cell Line Independently of Its Antioxidant Properties. Diotallevi Marina, Checconi Paola et al. Frontiers in Immunology. September 17, 2017 https://www.frontiersin.org/article/10.3389/fimmu.2017.01239
  1. The Role of N-Acetyl Cysteine in Pulmonary Tuberculosis. Resti Yudhawati, Nitya Prasanta. January 2020. Journal of Respiration https://e-journal.unair.ac.id/JR/article/download/17303/9706 
  1. Nair MP, Mahajan S, Reynolds JL, et al. The flavonoid quercetin inhibits proinflammatory cytokine (tumor necrosis factor alpha) gene expression in normal peripheral blood mononuclear cells via modulation of the NF-kappa beta system. Clin Vaccine Immunol. 2006;13(3):319‐328. doi:10.1128/CVI.13.3.319-328.2006  
  1. Leyva-López N, Gutierrez-Grijalva EP, Ambriz-Perez DL, Heredia JB. Flavonoids as Cytokine Modulators: A Possible Therapy for Inflammation-Related Diseases. Int J Mol Sci. 2016;17(6):921. Published 2016 Jun 9. doi:10.3390/ijms17060921
  1. Cheng SC, Huang WC, S Pang JH, Wu YH, Cheng CY. Quercetin Inhibits the Production of IL-1beta-Induced Inflammatory Cytokines and Chemokines in ARPE-19 Cells via the MAPK and NF-κB Signaling Pathways. Int J Mol Sci. 2019;20(12):2957. Published 2019 Jun 17. doi:10.3390/ijms20122957  
  1. Nair MP, Mahajan S, Reynolds JL, et al. The flavonoid quercetin inhibits proinflammatory cytokine (tumor necrosis factor alpha) gene expression in normal peripheral blood mononuclear cells via modulation of the NF-kappa beta system. Clin Vaccine Immunol. 2006;13(3):319‐328. doi:10.1128/CVI.13.3.319-328.2006 
  1. Hemilä H, Chalker E. Vitamin C Can Shorten the Length of Stay in the ICU: A Meta-Analysis. Nutrients. 2019;11(4):708. Published 2019 Mar 27. doi:10.3390/nu11040708 
  1. Bucca C, Rolla G, Arossa W, et al. Effect of ascorbic acid on increased bronchial responsiveness during upper airway infection. Respiration. 1989;55(4):214‐219. doi:10.1159/000195737 
  1. N-Acetylcysteine Protection in COPD. Wu, Wenxin et al. CHEST, Volume 145, Issue 1, 193-194. January 2014  
  1. Gammoh, N.Z.; Rink, L. Zinc in Infection and Inflammation. Nutrients2017, 9, 624.  
  1. Hirano T, Murakami M, Fukada T, Nishida K, Yamasaki S, Suzuki T. Roles of zinc and zinc signaling in immunity: zinc as an intracellular signaling molecule. Adv Immunol. 2008;97:149‐176. doi:10.1016/S0065-2776(08)00003-5  
  1. Changes in cytokine production and T cell subpopulations in experimentally induced zinc-deficient humans. F. W. Beck, A. S. Prasad, J. Kaplan, J. T. Fitzgerald, and G. J. Brewer. American Journal of Physiology-Endocrinology and Metabolism 1997 272:6, E1002-E1007 
  1. Prasad AS. Effects of zinc deficiency on Th1 and Th2 cytokine shifts. J Infect Dis. 2000;182 Suppl 1:S62‐S68. doi:10.1086/315916  
  1. Shen Y, Cai W, Lei S, Zhang Z. Effect of high/low dose N-acetylcysteine on chronic obstructive pulmonary disease: a systematic review and meta-analysis. COPD. 2014;11(3):351‐358. doi:10.3109/15412555.2013.85831 
  1. Fowdar K, Chen H, He Z, et al. The effect of N-acetylcysteine on exacerbations of chronic obstructive pulmonary disease: A meta-analysis and systematic review. Heart Lung. 2017;46(2):120‐128. doi:10.1016/j.hrtlng.2016.12.004  
  1. Cazzola M, Calzetta L, Facciolo F, Rogliani P, Matera MG. Pharmacological investigation on the anti-oxidant and anti-inflammatory activity of N-acetylcysteine in an ex vivo model of COPD exacerbation. Respir Res. 2017;18(1):26. Published 2017 Jan 24. doi:10.1186/s12931-016-0500-y  
  1. Santus P, Corsico A, Solidoro P, Braido F, Di Marco F, Scichilone N. Oxidative stress and respiratory system: pharmacological and clinical reappraisal of N-acetylcysteine. COPD. 2014;11(6):705‐717. doi:10.3109/15412555.2014.898040  
  1. De Backer J, Vos W, Van Holsbeke C, et al. Effect of high-dose N-acetylcysteine on airway geometry, inflammation, and oxidative stress in COPD patients. Int J Chron Obstruct Pulmon Dis. 2013;8:569‐579. doi:10.2147/COPD.S49307 
  1. Vitamin D reduces respiratory tract infections frequency. Bhutta, Zulfiqar A. The Journal of Pediatrics, Volume 186, 209 – 212 
  1. N-Acetylcysteine (NAC) inhibit mucin synthesis and pro-inflammatory mediators in alveolar type II epithelial cells infected with influenza virus A and B and with Respiratory Syncytial Virus (RSV) Mata, Manuel, Morcillo, Esteban et al. 2011/05/25. Biochemical pharmacology. 10.1016/j.bcp.2011.05.014 
  1. Schrauzer GN, Sacher J. Selenium in the maintenance and therapy of HIV-infected patients [published correction appears in Chem Biol Interact 1995 Feb;94(2):167]. Chem Biol Interact. 1994;91(2-3):199‐205. doi:10.1016/0009-2797(94)90040-x  
  1. N-Acetylcysteine: A New Approach to Anti-HIV Therapy. Mario Roederer, Stephen W. Ela, Frank J.T. Staal, Leonore A. Herzenberg, and Leonard A. Herzenberg. AIDS Research and Human Retroviruses 1992 8:2, 209-217  
  1. Kent L. Erickson, Edward A. Medina, Neil E. Hubbard, Micronutrients and Innate Immunity, The Journal of Infectious Diseases, Volume 182, Issue Supplement_1, September 2000, Pages S5-S10, https://doi.org/10.1086/315922
  1. Assimakopoulos SF, Marangos M. N-acetyl-cysteine may prevent COVID-19-associated cytokine storm and acute respiratory distress syndrome [published online ahead of print, 2020 Apr 22]. Med Hypotheses. 2020;140:109778. doi:10.1016/j.mehy.2020.109778  
  1. Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020;395(10229):1033‐1034. doi:10.1016/S0140-6736(20)30628-0 
  1. The pathogenesis and treatment of the ‘Cytokine Storm’ in COVID-19. Qing Ye, Bili Wang, Jianhua Mao. Journal of Infection. March 24, 2020. 
  1. Wu W, Li R, Li X, et al. Quercetin as an Antiviral Agent Inhibits Influenza A Virus (IAV) Entry. Viruses. 2015;8(1):6. Published 2015 Dec 25. doi:10.3390/v8010006  
  1. Hemilä H, Chalker E. Vitamin C may reduce the duration of mechanical ventilation in critically ill patients: a meta-regression analysis. J Intensive Care. 2020;8:15. Published 2020 Feb 7. doi:10.1186/s40560-020-0432-y
  1. Zinc-hydroxychloroquine Found Effective In Some COVID-19 Patients: Study. May 11, 2020. Barrons. Agence France Presse. https://www.barrons.com/news/zinc-hydroxychloroquine-found-effective-in-some-covid-19-patients-study-01589234407?tesla=y 
  1. Bernard GR, Wheeler AP, Arons MM, et al. A trial of antioxidants N-acetylcysteine and procysteine in ARDS. The Antioxidant in ARDS Study Group. Chest. 1997;112(1):164‐172. doi:10.1378/chest.112.1.164   
  1. Hydroxychloroquine and azithromycin plus zinc vs hydroxychloroquine and azithromycin alone: outcomes in hospitalized COVID-19 patients. Philip Carlucci, Tania Ahuja, Christopher M Petrilli, Harish Rajagopalan, Simon Jones, Joseph Rahimian. medRxiv 2020.05.02.20080036; doi: https://doi.org/10.1101/2020.05.02.20080036  
  1. Horowitz RI, Freeman PR, Bruzzese J. Efficacy of glutathione therapy in relieving dyspnea associated with COVID-19 pneumonia: A report of 2 cases [published online ahead of print, 2020 Apr 21]. Respir Med Case Rep. 2020;30:101063. doi:10.1016/j.rmcr.2020.101063
  1. Aditya Arya & Vivek Dhar Dwivedi (2020) Synergistic effect of vitamin D and remdesivir can fight
  1. COVID-19, Journal of Biomolecular Structure and Dynamics, DOI: 10.1080/07391102.2020.1773929 
  1. Meltzer, D., et al. (2020). Association of Vitamin D Deficiency and Treatment with COVID-19 Incidence medRxiv preprint. doi: https://doi.org/10.1101/2020.05.08.20095893. http://medrxiv.org/cgi/content/short/2020.05.08.20095893
  1. Rahman MT, Idid SZ. Can Zn Be a Critical Element in COVID-19 Treatment? [published online ahead of print, 2020 May 26]. Biol Trace Elem Res. 2020;1‐9. doi:10.1007/s12011-020-02194-9  
  1. Speeckaert, M.M., Delanghe, J.R. Association between low vitamin D and COVID-19: don’t forget the vitamin D binding protein. Aging Clin Exp Res (2020). https://doi.org/10.1007/s40520-020-01607-y