Host immune responses play central roles in controlling SARS-CoV2 infection, yet remain incompletely characterized and understood. Here, we present a comprehensive immune response map spanning 454 proteins and 847 metabolites in plasma integrated with single-cell multi-omic assays of 221,748 PBMCs in which whole transcriptome, 192 surface proteins, and T and B cell receptor sequence were analyzed within the context of clinical measures from 50 COVID19 patient samples. Our study reveals novel cellular subpopulations, such as proliferative exhausted CD8+ and CD4+ T cells, and cytotoxic CD4+ T cells, that may be features of severe COVID-19 infection. We condensed over 1 million immune features into a single immune response axis that independently aligns with many clinical features and is also strongly associated with disease severity. Our study represents an important resource towards understanding the heterogeneous immune responses of COVID-19 patients and may provide key information for informing therapeutic development.
Su, Yapeng and Chen, Daniel and Lausted, Christopher and Yuan, Dan and Choi, Jongchan and Dai, Cheng and Voillet, Valentin and Scherler, Kelsey and Troisch, Pamela and Duvvuri, Venkata R and Baloni, Priyanka and Qin, Guangrong and Smith, Brett and Kornilov, Sergey 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 Jones, Lesley and Zhou, Yong and Roper, Ryan and Mackay, Sean and O'Mahony, Shane and Dale, Christopher R. and Wallick, Julie A. and Algren, Heather A. and Michael, Zager A. and Magis, Andrew and Wei, Wei and Price, Nathan and Huang, Sui and Subramanian, Naeha and Wang, Kai and Hadlock, Jennifer and Hood, Leroy and Aderem, Alan and Bluestone, Jeffrey A. and Lanier, Lewis L. and Greenberg, Phil and Gottardo, Raphael and Davis, Mark M. and Goldman, Jason D and Heath, James and Unit, ISB-Swedish COVID19 Biobanking, Multiomic Immunophenotyping of COVID-19 Patients Reveals Early Infection Trajectories. Available at SSRN: https://ssrn.com/abstract=3659389 or http://dx.doi.org/10.2139/ssrn.3659389
This version of the paper has not been formally peer reviewed.
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