NRICM102 Ameliorates Pulmonary Embolism by Suppression of Inflammation, Prothrombotic/Fibrotic Factors Expression and Reduction of Alveolar Cell Apoptosis in SARS-CoV-2 Spike Protein-infected hACE2 mice

The prevalence of venous thromboembolic syndrome in hospitalized patients with COVID-19 is high. Our unpublished clinical data showed that a traditional Chinese medicine(TCM) NRICM101 can reduce the transfer rate of mild to moderate hospitalized patients with COVID-19 to ICU or intubation by 80% and NRICM102, another TCM remedy, can reduce mortality of severe to very severe hospitalized patients with COVID-19 by more than 50%. To examine the protective effect and mechanisms of NRICM102 on pulmonary embolism, K18-hACE2 transgenic mice infected with SARS-CoV2 spike protein S1 subunit was elucidated. NRICM102 treatment significantly ameliorated pulmonary embolism and improve arterial oxygen saturation (SO2%) from 84% to around 93%. NRICM102 could reduce S1 infection in lung tissue, ameliorate inflammatory responses by inhibiting neutrophil and macrophage activation/infiltration (MPO, Ly6G, CD11b, p65NF?B), reduce expression level of prothrombotic (NET, vWF, PAI-1) and fibrotic (c-Kit, SCF) factors and suppress AT1/AT2 alveolar cell apoptosis to achieve its lung protecting effect on this pulmonary embolism model. We conclude that NRICM102 is highly valuable and beneficial in the treatment of SARS-CoV-2 infection associated pulmonary disorders.