A Randomized, Single-blind, Group sequential, Active-controlled Study to evaluate the clinical efficacy and safety of a-Lipoic acid for critically ill patients with coronavirus disease 2019(COVID-19)

Ming Zhong; Aijun Sun; Ting Xiao; Ge Yao; Ling Sang; Xia Zheng; Jinyan Zhang; Xuejuan Jin; Lei Xu; Wenlong Yang; Peng Wang; Kai Hu; Dingyu Zhang; Junbo Ge

Since December 2019, the novel coronavirus pneumonia 2019 (COVID-19) induced by severe acute respiratory coronavirus 2 (SARS-CoV-2) has become a worldwide pandemic and is overwhelming health care systems globally. Thus far, no therapeutics have yet been proven effective for the treatment of severe COVID-19, and the mortality rate of severe COVID-19 patients is high [1] [2] [3] [4] [5] . Pathological results suggested that the lung displayed diffuse alveolar damage. In addition, interstitial mononuclear inflammatory infiltrates, mainly lymphocytes, were observed in both lungs [6] . Moreover, several studies have shown that CRP, D-dimer and serum proinflammatory cytokines (IL-6, IL-1β, etc.) was increased in patients with severe COVID-19 [6] [7] [8] [9] . These findings suggested that the cytokine release syndrome (CRS) may be associated with COVID-19. CRS is a systemic inflammatory response that can be induced by infection and certain drugs. The sharp increase of pro-inflammatory cytokines is the main manifestation, which can cause damage to the heart, lungs and other organs [10] . Therefore, regulating systemic inflammatory response may be a key method for treating patients with COVID-19, and several clinical studies targeting CRS have been conducted [11] . Viral infection can also cause the production of reactive oxygen species (ROS), and ROS plays an important role in virus replication and invasion [12] , organ damage [13, 14] , and systemic inflammatory response [15] [16] [17] [18] [19] [20] .