美国哥伦比亚大学Sagi D. Shapira、Nicholas P. Tatonetti等研究人员，合作揭示了SARS-CoV-2感染不良结局中的免疫补体和凝血功能障碍。2020年8月3日，《自然—医学》在线发表了这一成果。

研究人员表示，了解SARS-CoV-2感染的病理生理学对治疗和公共卫生策略至关重要。病毒与宿主的相互作用可以指导疾病调节剂的发现，而蛋白质结构功能分析指向几种免疫途径是冠状病毒的靶标，包括补体和凝血。

Author: Vijendra Ramlall, Phyllis M. Thangaraj, Cem Meydan, Jonathan Foox, Daniel Butler, Jacob Kim, Ben May, Jessica K. De Freitas, Benjamin S. Glicksberg, Christopher E. Mason, Nicholas P. Tatonetti, Sagi D. Shapira

Issue&Volume: 2020-08-03

Abstract: Understanding the pathophysiology of SARS-CoV-2 infection is critical for therapeutic and public health strategies. Viral–host interactions can guide discovery of disease regulators, and protein structure function analysis points to several immune pathways, including complement and coagulation, as targets of coronaviruses. To determine whether conditions associated with dysregulated complement or coagulation systems impact disease, we performed a retrospective observational study and found that history of macular degeneration (a proxy for complement-activation disorders) and history of coagulation disorders (thrombocytopenia, thrombosis and hemorrhage) are risk factors for SARS-CoV-2-associated morbidity and mortality—effects that are independent of age, sex or history of smoking. Transcriptional profiling of nasopharyngeal swabs demonstrated that in addition to type-I interferon and interleukin-6-dependent inflammatory responses, infection results in robust engagement of the complement and coagulation pathways. Finally, in a candidate-driven genetic association study of severe SARS-CoV-2 disease, we identified putative complement and coagulation-associated loci including missense, eQTL and sQTL variants of critical complement and coagulation regulators. In addition to providing evidence that complement function modulates SARS-CoV-2 infection outcome, the data point to putative transcriptional genetic markers of susceptibility. The results highlight the value of using a multimodal analytical approach to reveal determinants and predictors of immunity, susceptibility and clinical outcome associated with infection.

DOI: 10.1038/s41591-020-1021-2

Source: https://www.nature.com/articles/s41591-020-1021-2