1. Multiple early factors anticipate post-acute COVID-19 sequelae
- Author
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Su, Yapeng, Yuan, Dan, Chen, Daniel G, Ng, Rachel H, Wang, Kai, Choi, Jongchan, Li, Sarah, Hong, Sunga, Zhang, Rongyu, Xie, Jingyi, Kornilov, Sergey A, Scherler, Kelsey, Pavlovitch-Bedzyk, Ana Jimena, Dong, Shen, Lausted, Christopher, Lee, Inyoul, Fallen, Shannon, Dai, Chengzhen L, Baloni, Priyanka, Smith, Brett, Duvvuri, Venkata R, Anderson, Kristin G, Li, Jing, Yang, Fan, Duncombe, Caroline J, McCulloch, Denise J, Rostomily, Clifford, Troisch, Pamela, Zhou, Jing, Mackay, Sean, DeGottardi, Quinn, May, Damon H, Taniguchi, Ruth, Gittelman, Rachel M, Klinger, Mark, Snyder, Thomas M, Roper, Ryan, Wojciechowska, Gladys, Murray, Kim, Edmark, Rick, Evans, Simon, Jones, Lesley, Zhou, Yong, Rowen, Lee, Liu, Rachel, Chour, William, Algren, Heather A, Berrington, William R, Wallick, Julie A, Cochran, Rebecca A, Micikas, Mary E, Unit, the ISB-Swedish COVID-19 Biobanking, Wrin, Terri, Petropoulos, Christos J, Cole, Hunter R, Fischer, Trevan D, Wei, Wei, Hoon, Dave SB, Price, Nathan D, Subramanian, Naeha, Hill, Joshua A, Hadlock, Jennifer, Magis, Andrew T, Ribas, Antoni, Lanier, Lewis L, Boyd, Scott D, Bluestone, Jeffrey A, Chu, Helen, Hood, Leroy, Gottardo, Raphael, Greenberg, Philip D, Davis, Mark M, Goldman, Jason D, and Heath, James R
- Subjects
Clinical Research ,Prevention ,Infectious Diseases ,Good Health and Well Being ,Adaptive Immunity ,Adolescent ,Adult ,Aged ,Aged ,80 and over ,Autoantibodies ,Biomarkers ,Blood Proteins ,CD8-Positive T-Lymphocytes ,COVID-19 ,Convalescence ,Disease Progression ,Female ,Humans ,Immunity ,Innate ,Longitudinal Studies ,Male ,Middle Aged ,Risk Factors ,SARS-CoV-2 ,Transcriptome ,Young Adult ,Post-Acute COVID-19 Syndrome ,ISB-Swedish COVID-19 Biobanking Unit ,PASC ,RNAemia ,antibodies ,auto-antibodies ,computational biology ,immune system ,immunology ,long COVID ,metabolomics ,multi-omics ,proteomics ,single cell ,single-cell CITE-seq ,single-cell RNA-seq ,single-cell TCR-seq ,single-cell secretome ,symptoms ,transcriptome ,viremia ,Biological Sciences ,Medical and Health Sciences ,Developmental Biology - Abstract
Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data and patient-reported symptoms. We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific auto-antibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes, exhibiting divergent acute severity and PASC. We find that immunological associations between PASC factors diminish over time, leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.
- Published
- 2022