Doctor of Growth Medicine, Shi Hanping, MD, Atsuo Yanagisawa, MD, Thomas Levy, MD, JD, Andrew Saul
The cause of neo-pneumonitis (NCP) death from 2019-nCov is respiratory (ARDS) and multiple organ failure. ARDS is a “inflammatory factor storm” caused by the release of a large number of inflammatory factors, and the essence of the inflammatory factor storm is an increase in oxidative stress. A large number of timely antioxidants, especially a large number of timely intravenous C injections (IVC), combined with conventional supportive therapy are the special treatments for ARDS, reducing NCP mortality and promoting NCP recovery.
2019-nCov pneumonia (NCP), which originated in Wuhan, China, is currently spreading to many other countries, which greatly affects the health, livelihood and economy of the Chinese people and has attracted global attention. Unfortunately, there are no vaccines or specific antivirals for 2019-nCov. We urgently need a fast, rapid deployment and use of effective and safe treatment methods, which can not only save these patients, reduce the spread of epidemics, but also play an important role in providing psychological protection for people all over the world, especially the Chinese people. Acute organ failure, especially lung failure (Acute Respiratory Distress Syndrome, ARDS) is the key mechanism leading to 2019-nCov deaths. Due to the rapid release of free radicals and cytokines, a significant increase in oxidative stress is a hallmark of ARDS, which causes cell damage, organ failure, and death. Therefore, early use of high-dose antioxidants, especially vitamin C, plays a key role in the treatment of these patients. We call on all leaders and clinical staff to bravely and quickly apply large doses of intravenous Vit C to help these patients and stop the epidemic.
2019-nCov is a rapidly developing epidemic with high morbidity and mortality.
In a report of a study of 138 confirmed NCP cases, Wang et al. Reported an ICU occupancy rate of 26% and a mortality rate of 4.3% . In another case analysis of 99 confirmed NCP cases, 17 (17%) patients developed acute respiratory distress syndrome, of which 11 (11%) patients deteriorated in the short term and died of multiple organ failure [ 2].
Increased oxidative stress caused by a potential “cytokine storm” leads to ARDS, a key pathology for the high mortality of these pandemic virus infections.
ARDS caused by “cytokine storm” is the key pathology leading to the death of these patients . Coronaviruses and influenza are among the pandemic viruses that can cause fatal lung injury and death from ARDS . Virus infection caused “cytokine storm”, which can activate pulmonary capillary endothelial cells, resulting in increased neutrophil infiltration and increased oxidative stress (active oxygen and reactive nitrogen), further damaging the lung barrier function . ARDS, characterized by severe hypoxemia, is often accompanied by uncontrolled inflammation, oxidative damage, and damage to the alveolar-capillary barrier . Increased oxidative stress is the main damage to lung injury, such as acute lung injury (ALI) and ARDS, which are two clinical manifestations of acute respiratory failure, with high morbidity and mortality [5,6].
Of the 29 2019-nCov pneumonia diagnosed patients, 27 (93%) showed elevated hsCRP, which is one of the signs of elevated oxidative stress . Nrf2 is a major regulator of cytoprotective protein expression driven by antioxidant response elements (AREs). The activation of Nrf2 signaling plays a vital role in preventing cells and tissues from being induced by oxidative stress. Antioxidant systems in cellular responses include proteins (such as enzymes) or small molecules (such as vitamins C and E) . Nabzdyk and Bittner of Harvard Medical School (Massachusetts General Hospital) recently published an article in the World Journal of Critical Medicine, which provides a good overview of some of the biological effects of vitamin C in critical management :
- Antioxidants, free radical oxygen scavengers protect cells from oxidation;
- Synthesis of steroids and catecholamines, cofactors for catecholamines, vasopressin and steroid synthesis, improve hemodynamics and may accelerate the resolution of shock;
- Immune cell function. Increase phagocytosis and chemotaxis of neutrophils, affect the migration of macrophages, enhance the proliferation of T and NK cells, regulate their functions, and possibly increase antibody formation;
- Endothelial cell function. Reduce endothelial ICAM expression and leukocyte adhesion, improve endothelial barrier function, and improve microcirculation;
- Carnitine production, regulating fatty acid metabolism, may improve microcirculation and heart function;
- Wound healing, cofactor for collagen synthesis, mitogen for fibroblasts.
Antioxidants, especially high-dose intravenous VC drip (IVC) for ARDS.
It is clear that increased oxidative stress plays an important role in the pathogenesis of ARDS and NCP deaths. A cytokine storm has been observed in both viral and bacterial infections . Cytokine storms appear to be a common and non-specific pathway that leads to increased oxidative stress, ARDS and death. This information is important in clinical management. Since it seems logical to prevent and manage against increased oxidative stress with high-dose antioxidants, and can be applied to these deadly virus pandemics without waiting for pathogen-specificity as long as the current 2019-nCov epidemic Vaccines and drugs. In fact, high-dose intravenous vitamin C (IVC) has been successfully used clinically for viral ARDS and influenza . Fowler et al. Described a 20-year-old woman with viral ARDS (rhinus and enterovirus D68) . After the onset, her condition deteriorated quickly and she was admitted to the ICU. After the standard treatment failed, she started receiving ECMO (external oxygen exchange) on day 3. Large doses of IVC were also started on ECMO day 1, 200 mg / kg body weight / 24 hours, divided into 4 times, once every 6 hours. The day after the high-dose IVC infusion, an X-ray examination showed a marked improvement in her lung disease. After continuous use of ECMO and high-dose IVC, her condition improved rapidly and she stopped using ECMO on day 7 of ECMO. The patient recovered and was discharged on the 12th day of admission without supplemental oxygen. A month later, a radiograph of her lungs showed complete recovery. Gonzalez et al. (Including Thomas Levy, one of the authors) recently reported a severe case of flu, which was successfully treated with high-dose IVC . The 25-year-old MG developed flu-like symptoms while on vacation in Florida and quickly deteriorated. After about 2 weeks, the patient was almost powerless to go to the toilet. After Dr. Gonzales’s consultation, the patient was prescribed a large dose of IVC (50 g of Vit C in 1000 ml of Ringer’s solution, injected within 90 minutes). The patient immediately reported significant improvement the next day. On day 4 of the IVC infusion, he reported feeling normal. After healing, he continued to take VC (2 g , Three times a day) . Another story is widely spread on social media. According to reports, in 2009 New Zealand farmer Alan Smith contracted swine flu while traveling, lived in the ICU, and used ECMO. After being announced to abandon treatment by the hospital, with all the efforts of family members, the patient finally used a large dose of IVC, and the patient improved significantly the next day. A patient who was declared dead by the hospital and abandoned treatment was eventually rescued from the death line by IVC (Primal Panacea). One of us (Thomas Levy) was a consultant for this case [11-12]. Hemila et al analyzed the length of stay of VC and ICU in a meta-analysis of 18 clinical studies in 2019. They found that Vit C shortened ICU dwell time. The study, published in the journal Nutrients, involved a total of 2004 ICU patients . In the report, VC shortened the ICU stay in 1766 patients by 97.8%. In addition, Marik et al. Reported their use of IVC in 47 cases of sepsis ICU. They found that patients in the IVC group had a significant reduction in mortality .
Dietary antioxidants (vitamin C and sulforaphane) can reduce acute inflammatory lung injury caused by oxidative stress in mechanically ventilated patients  .
Other antioxidants (curcumin) have also been shown to have promising anti-inflammatory potential in pneumonia .
High-dose IVC has been used clinically for decades, and recent NIH expert panel documents clearly state that high-dose IVC (1.5 g / kd body weight) is safe and has no major side effects .
2019-nCov pneumonia (NCP) is a rapidly developing epidemic with high morbidity and mortality. The key mechanism of severe NCP is acute lung injury caused by inflammatory storm, leading to ARDS and death. Coronaviruses, influenza viruses, and many other pandemic viral infections are often associated with increased oxidative stress, which increases oxidative stress and leads to multiple organ failure. Therefore, in addition to standard conventional supportive therapies, the administration of antioxidants also plays a central role in the treatment of these diseases. Existing clinical studies and case reports indicate that early administration of high-dose IVC can improve the clinical status of patients with ICU, ARDS and influenza. It should be noted that large epidemics like 2019-nCov will happen in the future. Given that high-dose IVC is safe and effective, we call on leaders and healthcare professionals to immediately investigate the clinical use of high-dose IVC. More clinical research is needed on IVC and oral VCs (such as liposome-encapsulated VCs) to develop standard protocols for current use, and there is an urgent need for future use.
The development of special vaccines and antiviral drugs for each newly emerging virus is relatively long and cannot be put into clinical use quickly. Therefore, the development of vaccines and specific antiviral drugs is just one option. In view of the common pathogenic mechanism of these epidemics, inflammatory storms, oxidative stress, early large doses of antioxidants such as IVC and nutritional support are the best strategies! This strategy can not only be used for 2019-nCov NCP but also we can accumulate and summarize experience, and we will be well prepared for the next pandemic.
1. Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Feb 7;
2. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet Lond Engl. 2020 Jan 30;
3. Fowler III AA, Kim C, Lepler L, Malhotra R, Debesa O, Natarajan R, Fisher BJ, Syed A, DeWilde C, Priday A, Kasirajan V. Intravenous vitamin C as adjunctive therapy for enterovirus / rhinovirus induced acute respiratory distress syndrome. World J Crit Care Med. 2017 Feb 4; 6 (1): 85-90.
4. Meng L, Zhao X, Zhang H. HIPK1 Interference Attenuates Inflammation and Oxidative Stress of Acute Lung Injury via Autophagy. Med Sci Monit Int Med J Exp Clin Res. 2019 Jan 29; 25: 827-35.
5. Yan X, Fu X, Jia Y, Ma X, Tao J, Yang T, Ma H, Liang X, Liu X, Yang J, Wei J. Nrf2 / Keap1 / ARE Signaling Mediated an Antioxidative Protection of Human Placental Mesenchymal Stem Cells of Fetal Origin in Alveolar Epithelial Cells. Oxid Med Cell Longev. 2019; 2019: 2654910.
6. Hecker L. Mechanisms and consequences of oxidative stress in lung disease: therapeutic implications for an aging populace. Am J Physiol Lung Cell Mol Physiol. 2018 01; 314 (4): L642-53.
7. Chen L, Liu HG, Liu W, Liu J, Liu K, Shang J, Deng Y, Wei S. [Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia]. Zhonghua Jie He He Hu Xi Za Zhi Zhonghua Jiehe He Huxi Zazhi Chin J Tuberc Respir Dis. 2020 Feb 6; 43 (0): E005.
8. Liu Q, Gao Y, Ci X. Role of Nrf2 and Its Activators in Respiratory Diseases. Oxid Med Cell Longev. 2019; 2019: 7090534.
9. Nabzdyk CS, Bittner EA. Vitamin C in the critically ill-indications and controversies. World J Crit Care Med. 2018 Oct 16; 7 (5): 52-61.
10. High Dose Vitamin C and Influenza: A Case Report-ISOM [Internet]. [Cited 2020 Feb 9]. Available from: https://isom.ca/article/high-dose-vitamin-c-influenza-case- report /? from = groupmessage & isappinstalled = 0
11. Levy T. Primal Panacea. MedFox Publishing; 350 p. (Kindle Edition).
12. Levy TE. Primal Panacea. Medfox Pub, 2012. Kindle, 2017.
13. Hemilä H, Chalker E. Vitamin C Can Shorten the Length of Stay in the ICU: A Meta-Analysis. Nutrients. 2019 Mar 27; 11 (4).
14. Marik PE, Khangoora V, Rivera R, Hooper MH, Catravas J. Hydrocortisone, Vitamin C, and Thiamine for the Treatment of Severe Sepsis and Septic Shock: A Retrospective Before-After Study. Chest. 2017; 151 (6): 1229-38.
15. Patel V, Dial K, Wu J, Gauthier AG, Wu W, Lin M, Espey MG, Thomas DD, Jr CRA, Mantell LL. Dietary Antioxidants Significantly Attenuate Hyperoxia-Induced Acute Inflammatory Lung Injury by Enhancing Macrophage Function via Reducing the Accumulation of Airway HMGB1. Int J Mol Sci. 2020 Feb 1; 21 (3).
16. Zhang B, Swamy S, Balijepalli S, Panicker S, Mooliyil J, Sherman MA, Parkkinen J, Raghavendran K, Suresh MV. Direct pulmonary delivery of solubilized curcumin reduces severity of lethal pneumonia. FASEB J Off Publ Fed Am Soc Exp Biol . 2019 Dec; 33 (12): 13294-309.
17. High-Dose Vitamin C (PDQ (r))-Health Professional Version-National Cancer Institute [Internet]. [Cited 2020 Feb 9]. Available from: https://www.cancer.gov/about-cancer/treatment / cam / hp / vitamin-c-pdq
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