ABSTRACT
Background. Nitric Oxide (NO) has been previously demonstrated to have antimicrobial, anti-inflammatory, and vasodilator properties. Extensive work has been done in the clinical setting to explore these properties with iNO administered intermittently at high concentrations of 150-250 ppm. While viral CAP has gained major attention with the emergence of COVID-19, treatment methods remain limited and are challenging to develop. The purpose of this study is to assess iNO treatment administered to hospitalized adults with viral CAP. Methods. This is a randomized, open label multi-center ongoing study. Study population includes subjects aged 18-80, hospitalized for vCAP including COVID-19. Following enrollment, subjects were randomized 1:1 to either iNO [150ppm for 40 minutes, 4 times daily, up to 7 days in addition to standard supportive treatment (SST)], or control [SST alone]. iNO was delivered by LungFitTM, an innovative NO generator under development (Beyond Air, NY, USA). Follow up period is 180 days. Study endpoints include safety and the time to reach a stable saturation of >=93%. In addition, different other clinical parameters are collected to profile the effect of iNO in this population. Results. Analyzing the Intent To Treat (ITT) population (n=35, [16 iNO and 19 control]), safety profile of iNO treatment observed so far, was found to be favorable with no treatment related Adverse Events (AEs). Faster clinical improvement was noted in the iNO treatment group, paralleling CRP improvement between baseline to end of treatment (mean 2.7 mg/dl comparing treatment group [n=8] to control group [n=7], data not final). Conclusion. These data suggest that intermittent treatment with 150ppm iNO is safe and well tolerated and may contribute to faster clinical improvement in viral CAP. Different laboratory parameters may shed some light and help to characterize this observed effect, supporting the further exploration of iNO for the treatment of viral lower respiratory tract infection, including COVID-19.
ABSTRACT
Despite ongoing efforts to characterize the host response toward SARS-CoV-2, a major gap in our knowledge still exists regarding the magnitude and duration of the humoral response. Analysis of the antibody response in mild versus moderate/severe patients, using our new developed quantitative electrochemiluminescent assay for detecting IgM/IgA/IgG antibodies toward SARS-CoV-2 antigens, revealed a rapid onset of IgG/IgA antibodies, specifically in moderate/severe patients. IgM antibodies against the viral receptor binding domain, but not against nucleocapsid protein, were detected at early stages of the disease. Furthermore, we observed a marked reduction in IgM/IgA antibodies over-time. Adapting our assay for ACE2 binding-competition, demonstrated that the presence of potentially neutralizing antibodies is corelated with IgG/IgA. Finally, analysis of the cytokine profile in COVID-19 patients revealed unique correlation of an IL-12p70/IL33 and IgG seroconversion, which correlated with disease severity. In summary, our comprehensive analysis has major implications on the understanding and monitoring of SARS-CoV-2 infections.