Multiple early factors anticipate post-acute COVID-19 sequelae.

Authors

Yapeng Su, Institute for Systems Biology, Seattle, WAFollow
Dan Yuan, Institute for Systems BiologyFollow
Daniel G Chen, Institute for Systems Biology, Seattle, WA
Rachel H Ng, Institute for Systems Biology, Seattle, WA
Kai Wang, Institute for Systems Biology, Seattle, WA
Jongchan Choi, Institute for Systems Biology, Seattle, WA
Sarah Li, Institute for Systems Biology, Seattle, WA
Sunga Hong, Institute for Systems Biology, Seattle, WA
Rongyu Zhang, Institute for Systems Biology, Seattle, WA
Jingyi Xie, Institute for Systems Biology, Seattle, WA
Sergey A Kornilov, Institute for Systems Biology, Seattle, WAFollow
Kelsey Scherler, Institute for Systems Biology, Seattle, WA 98109, USAFollow
Ana Jimena Pavlovitch-Bedzyk
Shen Dong
Christopher Lausted, Institute for Systems Biology, Seattle, WA
Inyoul Lee, Institute for Systems Biology, Seattle, WA 98109, USAFollow
Shannon Fallen, Institute for Systems Biology, Seattle, WA
Chengzhen L Dai, Institute for Systems Biology, Seattle, WAFollow
Priyanka Baloni, Institute for Systems Biology, Seattle WA 98109.Follow
Brett Smith, Institute for Systems BiologyFollow
Venkata R Duvvuri, Institute for Systems BiologyFollow
Kristin G Anderson
Jing Li
Fan Yang
Caroline J Duncombe
Denise J McCulloch
Clifford Rostomily, Institute for Systems BiologyFollow
Pamela Troisch, Institute for Systems Biology, Seattle, WA
Jing Zhou
Sean Mackay
Quinn DeGottardi
Damon H May
Ruth Taniguchi
Rachel M Gittelman
Mark Klinger
Thomas M Snyder
Ryan Roper, Institute for Systems BiologyFollow
Gladys Wojciechowska, Institute for Systems Biology, Seattle, WA
Kim Murray, Institute for Systems Biology, Seattle, WA
Rick Edmark, Institute for Systems Biology, Seattle, WA
Simon Evans, Institute for Systems Biology, Seattle, WA
Lesley Jones, Institute for Systems Biology, Seattle, WA
Yong Zhou, Institute for Systems Biology, Seattle, WA, 98109, USAFollow
Lee Rowen, Institute for Systems Biology, Seattle, WA
Rachel Liu, Institute for Systems Biology, Seattle, WA
William Chour, Institute for Systems Biology, Seattle, WA
Heather A Algren, Swedish Medical Center - Swedish Center for Research and InnovationFollow
William R Berrington, Division of Infectious Diseases, Swedish Medical Center, Seattle, WA, USA, Swedish Center for Research and Innovation, Swedish Medical Center, Seattle, WA, USAFollow
Julie A Wallick, Swedish Medical Center - Swedish Center for Research and InnovationFollow
Rebecca A. Cochran, Swedish Center for Research and Innovation, Swedish Medical Center, Seattle, WA, 98109, USAFollow
Mary Micikas, Division of Infectious Diseases, Swedish Medical Center, Seattle, WA, USA, Swedish Center for Research and Innovation, Swedish Medical Center, Seattle, WA, USAFollow
ISB-Swedish COVID-19 Biobanking Unit, Institute for Systems Biology, Seattle, WA
Terri Wrin
Christos J Petropoulos
Hunter R Cole, St. John's Cancer Institute at Saint John's Health Center, Santa Monica, CA 90404, USA.
Trevan Fischer, St. John's Cancer Institute at Saint John's Health Center, Santa Monica, CA 90404, USA.Follow
Wei Wei, Institute for Systems Biology, Seattle, WAFollow
Dave Hoon, St. John's Cancer Institute at Saint John's Health Center, Santa Monica, CA 90404, USA.Follow
Nathan D Price, Institute for Systems Biology, Seattle, WA, USAFollow
Naeha Subramanian, Institute for Systems Biology, Seattle, WAFollow
Joshua A Hill
Jennifer J Hadlock, Institute for Systems Biology, Seattle, WA, USA.Follow
Andrew T Magis, Institute for Systems Biology, Seattle, Washington.Follow
Antoni Ribas
Lewis L Lanier
Scott D Boyd
Jeffrey A Bluestone
Helen Chu
Leroy Hood, Institute for Systems Biology, Seattle, Washington, United States of America.Follow
Raphael Gottardo
Philip D Greenberg
Mark M Davis
Jason D Goldman, Division of Infectious Diseases Swedish Medical Center Seattle WA.Follow
James R Heath, Institute for Systems Biology, Seattle, USAFollow

Document Type

Article

Publication Date

3-3-2022

Publication Title

Cell

Keywords

washington; seattle; isb; covid-19; 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

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.

Department

Infectious Diseases

Department

Institute for Systems Biology

Department

Pathology & Laboratory Medicine

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