Heterogeneous immunological recovery trajectories revealed in post-acute COVID-19

Y Su,D Yuan,DG Chen, K Wang,J Choi, CL Dai,S Hong, R Zhang,J Xie

user-5f8411ab4c775e9685ff56d3(2021)

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摘要
The immunological picture of how different patients recover from COVID-19, and how those recovery trajectories are influenced by infection severity, remain unclear. We investigated 140 COVID-19 patients from diagnosis to convalescence using clinical data, viral load assessments, and multi-omic analyses of blood plasma and circulating immune cells. Immune-phenotype dynamics resolved four recovery trajectories. One trajectory signals a return to pre-infection healthy baseline, while the other three are characterized by differing fractions of persistent cytotoxic and proliferative T cells, distinct B cell maturation processes, and memory-like innate immunity. We resolve a small panel of plasma proteins that, when measured at diagnosis, can predict patient survival and recovery-trajectory commitment. Our study offers novel insights into post-acute immunological outcomes of COVID-19 that likely influence long-term adverse sequelae. ### Competing Interest Statement JRH and AR are founders and board members of Isoplexis and PACT Pharma. MMD is a member of the Scientific Advisory Board of PACT Pharma. JAB is a member of the Scientific Advisory Boards of Arcus, Solid and VIR. JAB is a member of the Board of Directors of Gilead and Provention. JAB is the CEO of Sonoma Biotherapeutics. LLL is on the scientific advisory boards of Alector, Atreca, Dragonfly, DrenBio, Nkarta, Obsidian Therapeutics, SBI Biotech. RG has received consulting income from Juno Therapeutics, Takeda, Infotech Soft, Celgene, Merck and has received research support from Janssen Pharmaceuticals and Juno Therapeutics, and declares ownership in CellSpace Biosciences. PDG is on the Scientific Advisory Board of Celsius, Earli, Elpiscience, Immunoscape, Rapt, and Nextech, was a scientific founder of Juno Therapeutics, and receives research support from Lonza. JDG declared contracted research with Gilead, Lilly, and Regeneron. The remaining authors declare no competing interests. ### Funding Statement We acknowledge funding support from the Wilke Family Foundation (JRH), the Murdock Trust (JRH), Gilead Sciences (JRH), the Swedish Medical Center Foundation (JDG), the Parker Institute for Cancer Immunotherapy (JRH, MMD, PDG, LLL, AR and JAB), Merck, and the Biomedical Advanced Research and Development Authority (HHSO10201600031C to JRH). KW was funded by DOD (W911NF-17-2-0086), NIH (R01 DA040395 and UG3TR002884). RG was funded by the NIH Human Immunology Project Consortium (U19AI128914) and the Vaccine and Immunology Statistical Center (Bill and Melinda Gates Foundation OPP1032317). Further funding by NIH (AI068129 to LLL and R21 AI138258 to NS). YS was supported by the Mahan Fellowship at Herbold Computational Biology Program of Fred Hutch Cancer Research Center. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Procedures for the current study were approved by the Institutional Review Board (IRB) at Providence St. Joseph Health with IRB Study Number [STUDY2020000175] and the Western Institutional Review Board (WIRB) with IRB Study Number 20170658. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Due to the potential risk of de-identification of pseudonymized RNA sequencing data the raw data will be available under controlled access in the EGA repository upon journal acceptance. For access to data prior to journal acceptance, please contact the corresponding authors.
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关键词
heterogeneous immunological recovery trajectories,post-acute
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