@article {12349, title = {Multi-Omics Resolves a Sharp Disease-State Shift between Mild and Moderate COVID-19.}, journal = {Cell}, volume = {183}, year = {2020}, month = {2020 12 10}, pages = {1479-1495.e20}, abstract = {

We present an integrated analysis of the clinical measurements, immune cells, and plasma multi-omics of 139 COVID-19 patients representing all levels of disease severity, from serial blood draws collected during the first week of infection following diagnosis. We identify a major shift between mild and moderate disease, at which point elevated inflammatory signaling is accompanied by the loss of specific classes of metabolites and metabolic processes. Within this stressed plasma environment at moderate disease, multiple unusual immune cell phenotypes emerge and amplify with increasing disease severity. We condensed over 120,000 immune features into a single axis to capture how different immune cell classes coordinate in response to SARS-CoV-2. This immune-response axis independently aligns with the major plasma composition changes, with clinical metrics of blood clotting, and with the sharp transition between mild and moderate disease. This study suggests that moderate disease may provide the most effective setting for therapeutic intervention.

}, keywords = {Adolescent, Adult, Aged, Aged, 80 and over, COVID-19, Female, Genomics, Humans, Male, Middle Aged, RNA-Seq, SARS-CoV-2, Severity of Illness Index, Single-Cell Analysis}, issn = {1097-4172}, doi = {10.1016/j.cell.2020.10.037}, author = {Su, Yapeng and Chen, Daniel and Yuan, Dan and Lausted, Christopher and Choi, Jongchan and Dai, Chengzhen L and Voillet, Valentin and Duvvuri, Venkata R and Scherler, Kelsey and Troisch, Pamela and Baloni, Priyanka and Qin, Guangrong and Smith, Brett and Kornilov, Sergey A and Rostomily, Clifford and Xu, Alex and Li, Jing and Dong, Shen and Rothchild, Alissa and Zhou, Jing and Murray, Kim and Edmark, Rick and Hong, Sunga and Heath, John E and Earls, John and Zhang, Rongyu and Xie, Jingyi and Li, Sarah and Roper, Ryan and Jones, Lesley and Zhou, Yong and Rowen, Lee and Liu, Rachel and Mackay, Sean and O{\textquoteright}Mahony, D Shane and Dale, Christopher R and Wallick, Julie A and Algren, Heather A and Zager, Michael A and Wei, Wei and Price, Nathan D and Huang, Sui and Subramanian, Naeha and Wang, Kai and Magis, Andrew T and Hadlock, Jenn J and Hood, Leroy and Aderem, Alan and Bluestone, Jeffrey A and Lanier, Lewis L and Greenberg, Philip D and Gottardo, Raphael and Davis, Mark M and Goldman, Jason D and Heath, James R} }