Nitric Oxide (NO) inhalation to treat COVID-19: coupling in-situ NO-generating modules to ventilators

**COVID-19:** 2019年12月，武汉市卫生健康委员会确定了一起原因不明的病毒性肺炎疫情。在其中一些患者中很快发现了冠状病毒RNA。这种新型冠状病毒被命名为SARS-CoV-2，由这种病毒引起的疾病被定义为COVID-19。这种疾病现在已成为大流行病，确诊病例远远超过100万，死亡10万人，病死率至少比流感高出一个数量级。COVID-19对全球卫生保健系统和经济构成了重大挑战。**一氧化氮（NO）气体：**（不要与一氧化二氮（N2O）或二氧化氮（NO2）混淆）由人体自然产生，用于控制许多身体功能（例如血液流动，伤口愈合，炎症），并作为一种有效的抗菌剂（包括对抗耐药细菌，真菌和病毒）。NO吸入疗法是将控制浓度的NO气体通过呼吸机输送到患者肺部，是一种被批准的治疗多种呼吸系统疾病的方法。目前批准的NO吸入治疗系统混合NO气体，储存在大型压缩气瓶中，空气流动呼吸。目前，世界各地的几个研究小组正在研究NO吸入治疗和预防COVID-19的方法，这种疗法曾在2002年SARS爆发期间显示出希望。问题：假设该疗法在临床研究中有效，快速、广泛和具有成本效益的应用仍然存在主要障碍。目前使用压缩NO气瓶的系统价格昂贵（连续治疗数天每小时100英镑），而且只适用于小范围用途——扩大交付以应对COVID-19将是昂贵的，而且在后勤上不切实际。**潜在解决方案：**等离子体技术（电电离气体，固体、液体和气体之后的第四种物质状态）可以从空气（氮和氧）中原位产生NO。与现有的呼吸机串联在一起，Fourth State的紧凑、模块化和价格合理的等离子设备可以智能地将空气中的NO输送到肺部，只使用电力作为输入。我们的设备先前已由英国大学独立验证，可生产数量可控的NO，并具有相应的已知生物效应（抗菌作用，加速伤口愈合过程）。

**COVID-19:** in December 2019, the Wuhan Municipal Health Committee identified an outbreak of viral pneumonia of unknown cause. Coronavirus RNA was quickly identified in some of these patients. This novel coronavirus has been designated SARS-CoV-2, and the disease caused by this virus defined as COVID-19\. This disease has now become pandemic, and with well over 1 million confirmed cases, 100,000 deaths and a case fatality rate that exceeds that of influenza by at least an order of magnitude. COVID-19 represents a substantial challenge to healthcare systems and economies worldwide.**Nitric Oxide (NO) gas:** (not to be confused with Nitrous Oxide, N2O, or Nitrogen Dioxide, NO2) is produced naturally by the body for controlling numerous bodily functions (e.g. blood flow, wound healing, inflammation) and as a potent antimicrobial (including against drug-resistant bacteria, fungi and viruses). NO inhalation therapy, in which NO gas in controlled concentrations is delivered to patients' lungs via ventilators, is an approved treatment for a number of respiratory conditions. Currently approved NO inhalation therapy systems mix NO gas, stored in large compressed gas cylinders, with air flow for breathing. NO inhalation is currently being investigated by several research groups worldwide for treatment and prevention of COVID-19 - the therapy previously showed promise during the 2002 SARS outbreak.**Problem:** assuming the therapy works in clinical studies, key barriers remain to rapid, widespread and cost-effective deployment. Current systems using compressed NO gas cylinders are prohibitively expensive (£100/hour over several days of continuous treatment) and only available for niche use - scaling up delivery to address COVID-19 would be expensive and logistically impractical.**Potential solution:** plasma technology (electrically ionised gas, the fourth state of matter after solid, liquid and gas) can produce NO in-situ from air (nitrogen and oxygen). Coupled in-line to existing ventilators, Fourth State's compact, modular and affordable plasma devices could intelligently deliver NO in the flow of air to the lungs, using just electricity as an input. Our devices have previously been independently verified by UK universities to produce NO in controlled quantities, with corresponding known biological effects (antimicrobial action, accelerated wound healing processes).