今日在美國醫(yī)學(xué)在線新聞（MEDPAGE）上發(fā)表的一篇新文章報道了三例接受三氧治療的重度Covid-19肺炎患者的病情得到了徹底而迅速的恢復(fù)。

三氧療法在歐洲廣泛使用，并且在治愈Covid-19患者方面取得了令人難以置信的成功。

這是美國第一篇有關(guān)三氧療法對Covid-19的益處的發(fā)表文章，文章引用了發(fā)表在《美國案例報告雜志》臨床案例。

小編將發(fā)表在《美國案例報告雜志》文獻編譯分享。

氧氣-三氧療法在治療COVID-19肺炎中的潛在作用

阿爾貝托·埃爾南德斯（AlbertoHernández），蒙特塞拉特·維納爾斯（MontserratVi?als），托馬斯·伊西多羅（Tomas Isidoro），弗朗西斯科·維拉斯（FranciscoVilás）

（西班牙伊維薩島Policlinica Ibiza醫(yī)院麻醉科）

2020年Am J Case Rep；21：e925849 DOI：10.12659 / AJCR.925849

案例

患者：男性，49歲；男性，61歲；女性，64歲

最終診斷：COVID-19

癥狀：呼吸困難

藥物治療：-

臨床過程：-

專科：感染性疾病 - 肺病學(xué)

Background

Ozone (O3 ) is a gas composed of 3 atoms of oxygen, including a stable pair (O2 ) and a third, unstable, atom, which gives ozone its beneficial effects. Medical ozone generators produce 1–5%ozone gas in 95–99% oxygen from pure oxygen. For medical purposes, concentrations of 10–70 μg/mL are commonly used. Ozone therapy can be administered systemically by adding it to a sample of a patient’s own blood and then reinfusing it, in what is termed “ozonated autohemotherapy.” When blood is exposed to this gas mixture (O2 –O3 ), oxygen equilibrates with the extracellular and intraerythrocytic water before becoming bound to hemoglobin until it is fully oxygenated; in contrast, ozone, which is about 10 times more soluble than oxygen, allows its immediate reaction with any soluble compounds and biomolecules present in biological fluids, readily dissolves in water, and reacts instantaneously with several biomolecules such as ascorbic acid, urate, free cysteine, glutathione molecules, and albumin thiol groups, and then disappears. The compounds generated during the reactions (reactive oxygen species and lipid ozonation products) are the “ozone messengers” and are responsible for its biological and therapeutic effects. O2 –O3 therapy has many beneficial effects, including inactivation of microorganisms such as viruses, modulation of the immune system, improvement of microcirculation, anti-inflammatory action stimulation of oxygen metabolism, and promotion of tissue oxygenation.

背景

三氧(O3)是一種由3個氧原子組成的氣體，包括可穩(wěn)定的對(O2)和第三個不穩(wěn)定的原子，這使三氧具有有益的作用。醫(yī)用臭氧發(fā)生器從95-99%的純氧中產(chǎn)生1-5%的三氧氣體。在醫(yī)療上，常用濃度為10-70μg/mL。三氧治療可以通過將其加入到患者自身的血液樣本中，然后再注入，即所謂的 "三氧自體血療法"，進行系統(tǒng)性的治療。當(dāng)血液暴露在這種混合氣體(O2 -O3 )中時，氧氣與細胞外和紅細胞內(nèi)的水平衡，然后與血紅蛋白結(jié)合，直到完全含氧。相反，三氧的溶解度約為氧氣的10倍，可使其立即與生物液中存在的任何可溶性化合物和生物分子發(fā)生反應(yīng)，易溶于水，并與抗壞血酸、尿酸鹽、游離半胱氨酸、谷胱甘肽分子和白蛋白硫醇基等幾種生物分子瞬間反應(yīng)，然后消失。反應(yīng)過程中產(chǎn)生的化合物(活性氧和脂質(zhì)三氧化產(chǎn)物)是 "三氧信使"，是其生物和治療作用的原因。

O2-O3療法有許多有益的作用，包括滅活病毒等微生物，調(diào)節(jié)免疫系統(tǒng)，改善微循環(huán)，抗炎作用刺激氧代謝，促進組織氧合。

Case Reports

Three patients presenting with severe COVID-19 pneumonia had marked and rapid clinical improvement after O2 –O3 therapy. Informed consent was obtained from all 3 patients. Ozonated autohemotherapy involved intravenous infusion of ozonated autologous whole blood. Initially, 200 mL of autologous whole blood was drawn from the antecubital vein into a standard plastic disposable blood collection bag (certified SANO3 bag) containing 35 mL of anticoagulant citrate dextrose solution. The blood was then enriched with 200 mL of gas mixture O2 –O3 with an ozone concentration of 40 μg/mL obtained using an Ozonobaric P Sedecal device, which is an ozone generator with CE0120 certificate type IIb. The ozonized blood was then slowly reinfused into the same vein over a period of approximately 10 min.

案例報告

3例出現(xiàn)重癥COVID-19肺炎的患者，經(jīng)過O2-O3治療后，臨床癥狀明顯快速改善。3例患者均獲得知情同意。起初，從肘中靜脈抽取200 mL自體全血到標準的一次性塑料采血袋（抗氧化處理）中，內(nèi)含35 mL抗凝劑(枸櫞酸鈉)。然后用200 mL的氣體混合物O2 -O3富集血液，三氧濃度為40 μg/mL。充分混合后，將三氧化的血液緩慢地重新回輸回同一靜脈中。

Case 1

A 49-year-old man (body mass index [BMI] 31 kg/m2 ) presented to the Emergency Department (ED) with abdominal discomfort for 1 week and progressive shortness of breath during the previous day. On examination, the abdomen was soft and lax, with no distension noted. Chest auscultation revealed bilateral crackles with reduced air entry. A computed tomography (CT) of the chest–abdomen revealed bilateral lung infiltrates compatible with COVID-19 pneumonia (Figure 1).

案例1

一名49歲的男性（體重指數(shù)[BMI]31 kg/m2）因腹部不適1周，前一天出現(xiàn)進行性氣促而到急診科就診。檢查時，腹部柔軟、松弛，未見腹脹。胸部聽診發(fā)現(xiàn)雙側(cè)裂紋，進氣減少。胸腹CT顯示雙側(cè)肺部浸潤，符合COVID-19肺炎（圖1）。

圖8：C反應(yīng)蛋白水平在三氧治療開始后立即下降

Discussion

We report successful use of ozone therapy in 3 patients with COVID-19 pneumonia in terms of precluding the need for invasive ventilation and early discharge to home after 4–6 sessions of ozonated autohemotherapy. There is no currently available effective treatment for COVID-19 pneumonia. The pathogenesis of the virus is not fully understood, but the pathological picture in the lungs varies significantly in terms of diffuse alveolar damage and microcirculopathy leading to life-threatening hypoxia . Ozone has multiple beneficial properties that could be useful in treatment of COVID-19 pneumonia.

討論

我們報道了3例COVID-19肺炎患者成功使用三氧治療，在排除了有創(chuàng)通氣的需要后，經(jīng)過4-6個療程的三氧自體血治療后提前出院回家。目前對COVID-19肺炎尚無有效的治療方法。該病毒的發(fā)病機制尚不完全清楚，但在肺部的病理表現(xiàn)差異很大，有彌漫性肺泡損傷和微循環(huán)病變，導(dǎo)致缺氧危及生命。三氧具有多種有益特性，可用于治療COVID-19肺炎。

Ozone can deliver sufficient energy and oxygen to the tissues through activating the pentose phosphate pathway, elevating 2,3-diphosphoglyceric acid content in erythrocytes, and stimulating erythrocyte oxygen metabolism . Furthermore, it improves the rheology and capillary action of the blood , which has been reported to be helpful for patients with ischemic vascular diseases . Additionally, ozone has an antiplatelet effect and increases release of some prostacyclins such as PGI2 , which are beneficial for patients with microthrombosis . All of these effects can help decrease the hypercoagulation phenomena observed in COVID-19 patients. Another important role played by ozone in COVID-19 is its immunomodulatory effects. The inflammatory response is a hallmark of severe infection, and cytokine modulation is key to avoid patient deterioration. Ozone has potent anti-inflammatory properties through modulation of the NLRP3 inflammasome, which plays a crucial role in the initiation and persistence of inflammation in various diseases . Ozone can also confer renal protection; the rate of kidney damage in COVID patients is significant, and ozone modulates the accumulation of neutrophils locally, the expression of interleukin (IL)-6, tumor necrosis factor (TNF)-a, and albumin modified by ischemia in the kidneys, and increases local antioxidant capacity .

三氧可以通過激活磷酸戊糖途徑，提高紅細胞中2，3-二磷酸甘油酯含量，刺激紅細胞氧代謝，為組織提供充足的能量和氧氣。此外，它還能改善血液的流變性和毛細血管的作用，據(jù)報道對缺血性血管疾病患者有幫助。此外，三氧還具有抗血小板作用，增加一些前列環(huán)素的釋放，如PGI2等，對微血栓形成患者有利。這些作用都有助于減少COVID-19患者觀察到的高凝現(xiàn)象。三氧在COVID-19中發(fā)揮的另一個重要作用是其免疫調(diào)節(jié)作用。炎癥反應(yīng)是嚴重感染的標志，細胞因子的調(diào)節(jié)是避免患者惡化的關(guān)鍵。三氧通過調(diào)控NLRP3炎癥體具有強效的抗炎作用，NLRP3炎癥體在各種疾病炎癥的啟動和持續(xù)中起著至關(guān)重要的作用[9]。三氧還可以賦予腎臟保護功能，COVID患者腎臟損傷率顯著，三氧可以調(diào)節(jié)腎臟局部中性粒細胞的積累、白細胞介素(IL)-6、腫瘤壞死因子(TNF)-a和缺血修飾的白蛋白的表達，增加局部抗氧化能力。

The effectiveness of ozone against pathogens is well known. Ozone can induce the release and modulation of interferons (IFNs) and related cytokines, such as IL-2, IFN-g, and TNF, and colony-stimulating factors , and can also modulate and stimulate phagocytic function , which can have a very positive effect in COVID-19 infection. Angiotensin-converting enzyme 2 (ACE-2) is an entry receptor for COVID [16]; the virus’s spike protein attaches to an ACE-2 receptor on the cell surface, mediating virus fusion with and entry into the host cell . This receptor can be blocked by control of the nuclear factor erythroid 2-related factor 2 (Nrf2), which regulates and blocks the activity of this receptor . Because ozone causes rapid Nrf2 activation , it seems very likely that this is an important physiological mechanism in blocking endogenous COVID-19 reduplication by preventing contact with this receptor.

三氧對病原體的有效性是眾所周知的。三氧可誘導(dǎo)干擾素（IFNs）及相關(guān)細胞因子如IL-2、IFN-g、TNF等和菌落刺激因子的釋放和調(diào)節(jié)，還可調(diào)節(jié)和刺激吞噬細胞功能，對COVID-19感染有非常積極的作用。血管緊張素轉(zhuǎn)換酶2(ACE-2)是COVID的進入受體，病毒的穗蛋白附著在細胞表面的ACE-2受體上，介導(dǎo)病毒與宿主細胞融合并進入宿主細胞。通過控制核因子紅細胞2相關(guān)因子2(Nrf2)，可以調(diào)節(jié)和阻斷該受體的活性。由于三氧會引起Nrf2的快速激活，似乎很有可能是通過阻止與該受體的接觸來阻斷內(nèi)源性COVID-19還原的重要生理機制。

Conclusions

O2 –O3 therapy appears to be effective in COVID-19 patients with severe respiratory failure; however, it is not yet an approved therapeutic technique. Large controlled clinical trials are required to study the efficacy and safety of using O2 –O3 therapy compared with standard supportive care in patients with COVID-19 in terms of the need for invasive ventilation and length of hospital and ICU stays.

結(jié)論

O2-O3療法似乎對COVID-19嚴重呼吸衰竭患者有效，但它還不是一種被批準的治療技術(shù)。需要進行大規(guī)模的對照臨床試驗，以研究在COVID-19患者中使用O2-O3療法與標準支持性護理相比，在有創(chuàng)通氣的需要和住院及ICU住院時間方面的有效性和安全性。

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