Protocol of a randomized controlled trial testing inhaled Nitric Oxide in mechanically ventilated patients with severe acute respiratory syndrome in COVID-19 (SARS-CoV-2).

Chong Lei; Binxiao Su; Hailong Dong; Andrea Bellavia; Raffaele Di Fenza; Bijan Safaee Fakhr; Stefano Gianni; Luigi Giuseppe Grassi; Robert Kacmarek; Caio Cesar Araujo Morais; Riccardo Pinciroli; Emanuele Vassena; Lorenzo Berra

[3]. The majority of the cases has been reported in China, but significant outbreaks are taking place in South Korea, Japan, Europe, Iran and more recently in USA [4] . In the human host, SARS-CoV-2 infection may be asymptomatic or may cause a syndrome (named COVID-19) ranging from common cold to a severe pneumonia with acute respiratory syndrome and need of mechanical ventilation in intensive care unit (ICU). In a retrospective Chinese study on 138 consecutive patients admitted with COVID-19, the median time from clinical onset to hospital admission was 7 days, 26% of patients were admitted to the ICU and 61% of them met clinical criteria for acute respiratory distress syndrome (ARDS) [5] . Another retrospective Chinese study on critically ill patients with COVID-19 pneumonia showed that 67% of patients met ARDS criteria, with a mortality of 61.5% at 28 days. Reported casualties in the ICU are characterized of various profiles of multiorgan failure (81% of deceased patients had ARDS, 37.5% had AKI, 28% had cardiac injury and 28% had liver failure) [6] . Autoptic findings in a published clinical case showed features resembling those of coronavirus-related infections such as Severe Acute Respiratory Distress Syndrome (SARS) and Middle Eastern Resporatory Syndrome (MERS), including bilateral diffuse alveolar damage with fibromyxoid exudates, desquamation of pneumocytes and hyaline membrane formation. Findings in cardiac and hepatic tissues may suggest the contribution of a viral infection as well [7] . COVID-19 is highly contagious and responsible for thousands of casualties and is now spreading to many countries. The combined effect of the high transmission and the reported high incidence of severe disease in symptomatic patients poses a threat to healthcare systems involved in the outbreaks in different ways, including: cumulative casualties, increased need for hospital and ICU beds causing work overload for all the healthcare staff and often forcing hospitals to shut down all elective surgical activity; high social and economic costs, dramatically reduction of the productivity by the rigorous quarantine requirements and strategies for curtailing disease spreading, which made economic pain that disrupt supply chains and stock markets .