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

**新冠肺炎：**2019年12月，武汉市卫健委确诊一起不明原因病毒性肺炎暴发疫情。在这些患者中，很快就发现了冠状病毒RNA。这种新型冠状病毒被命名为SARS-CoV-2，由该病毒引起的疾病定义为新冠肺炎。这种疾病现在已经成为一种流行病，确诊病例远远超过100万例，死亡10万人，病死率至少比流感高出一个数量级。新冠肺炎对世界各地的医疗体系和经济都是一个巨大的挑战。**一氧化氮(NO)气体：**(不要与一氧化二氮，N2O或二氧化氮，NO2混淆)是人体自然产生的，用于控制多种身体功能(例如，血流、伤口愈合、炎症)，并作为一种有效的抗菌剂(包括对抗抗药性细菌、真菌和病毒)。NO吸入疗法，即不通过呼吸机将受控浓度的气体输送到患者的肺部，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吸入治疗系统将储存在大型压缩气瓶中的NO气体与用于呼吸的气流混合在一起。世界各地的几个研究小组目前正在研究吸入NO治疗和预防新冠肺炎--这种疗法以前在2002年非典爆发期间曾显示出希望。**问题：**假设这种疗法在临床研究中有效，那么在快速、广泛和具有成本效益的部署方面仍然存在关键障碍。当前使用压缩NO气瓶的系统价格高得令人望而却步(连续治疗几天，每小时可达100 GB)，而且仅适用于小众市场--扩大送货规模以应对新冠肺炎的成本将是昂贵的，在物流上也不可行。**潜在的解决方案：**等离子体技术(电离气体，继固体、液体和气体之后的第四种物质状态)无法从空气(氮气和氧气)中原位产生NO。与现有的呼吸机串联在一起，第四州紧凑、模块化和负担得起的等离子设备可以智能地将NO输送到肺部，只需使用电力作为输入。我们的设备之前已经被英国大学独立验证，可以产生受控数量的NO，具有相应的已知生物学效应(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).