Multi-Omics Resolves a Sharp Disease-State Shift between Mild and Moderate COVID-19.

TitleMulti-Omics Resolves a Sharp Disease-State Shift between Mild and Moderate COVID-19.
Publication TypeJournal Article
Year of Publication2020
AuthorsSu, Y, Chen, D, Yuan, D, Lausted, C, Choi, J, Dai, CL, Voillet, V, Duvvuri, VR, Scherler, K, Troisch, P, Baloni, P, Qin, G, Smith, B, Kornilov, SA, Rostomily, C, Xu, A, Li, J, Dong, S, Rothchild, A, Zhou, J, Murray, K, Edmark, R, Hong, S, Heath, JE, Earls, J, Zhang, R, Xie, J, Li, S, Roper, R, Jones, L, Zhou, Y, Rowen, L, Liu, R, Mackay, S, D O'Mahony, S, Dale, CR, Wallick, JA, Algren, HA, Zager, MA, Wei, W, Price, ND, Huang, S, Subramanian, N, Wang, K, Magis, AT, Hadlock, JJ, Hood, L, Aderem, A, Bluestone, JA, Lanier, LL, Greenberg, PD, Gottardo, R, Davis, MM, Goldman, JD, Heath, JR
Corporate AuthorsISB-Swedish COVID19 Biobanking Unit
Date Published2020 12 10
KeywordsAdolescent, 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

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.

Alternate JournalCell
PubMed ID33171100
PubMed Central IDPMC7598382
Grant ListR21 AI138258 / AI / NIAID NIH HHS / United States
U19 AI057229 / AI / NIAID NIH HHS / United States
R01 DA040395 / DA / NIDA NIH HHS / United States
UG3 TR002884 / TR / NCATS NIH HHS / United States
R01 AI068129 / AI / NIAID NIH HHS / United States
U19 AI128914 / AI / NIAID NIH HHS / United States