Highly pathogenic coronavirus N protein aggravates lung injury by MASP-2-mediated complement over-activation

Ting Gao; Mingdong Hu; Xiaopeng Zhang; Hongzhen Li; Lin Zhu; Hainan Liu; Qincai Dong; Zhang Zhang; Zhongyi Wang; Yong Hu; Yangbo Fu; Yanwen Jin; Kaitong Li; Songtao Zhao; Yongjiu Xiao; Shuping Luo; Lufeng Li; Lingfang Zhao; Junli Liu; Huailong Zhao; Yue Liu; Weihong Yang; Jing Peng; Xiaoyu Chen; Ping Li; Yaoning Liu; Yonghong Xie; Jibo Song; Lu Zhang; Qingjun Ma; Xiuwu Bian; Wei Chen; Xuan Liu; Qing Mao; Cheng Cao

Thirdly, we've observed an excessive activation of complement cascade in lung tissue of dead patient, which is coincident with the observation in Ad-SARS N pre-infected and LPSprimed mice model. High-level C5a was accumulated in the serum of severe but not mild COVID-19 patients (Fig. 3 and 4) . So, it will make sense that complement cascade-targeted 25 immunomodulation may be effective for inflammation-control in highly pathogenic coronavirusrelated diseases. In this pathway, C5a is the most potent complement protein triggering inflammation. Blockage of C5a signaling has also been reported to improve treatment of acute lung injury (ALI) induced by highly pathogenic viruses (39) . Based on our scientific finding and the good safety record in phase II trial for other disease by Staidson and InflaRx GmbH (whom 30 produce the anti-C5a antibody in the same cell line), the recombinant anti-C5a antibody produced by Staidson Biopharmaceuticals was approved by NMPA for the clinical trial for treatment of severe and critical COVID-19 patients. At least in the first two patients, both are in the disease deterioration, the anti-C5a antibody showed rapid and promising effect exceeding the expect of clinical physicians. Although the final efficacy will be released until the clinical trial is 35 finished, it is worth to expect that anti-C5a antibody would provide a new approach for the treatment of COVID-19. the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.