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Published, Version of Record (VoR)Open Access (License Unspecified), Open
Preprint
Unraveling SARS-CoV-2 Host-Response Heterogeneity through Longitudinal Molecular Subtyping
bioRxiv
25 Nov 2024
PMID: 39651165
Abstract
Hospitalized COVID-19 patients exhibit diverse immune responses during acute infection, which are associated with a wide range of clinical outcomes. However, understanding these immune heterogeneities and their links to various clinical complications, especially long COVID, remains a challenge. In this study, we performed unsupervised subtyping of longitudinal multi-omics immunophenotyping in over 1,000 hospitalized patients, identifying two critical subtypes linked to mortality or mechanical ventilation with prolonged hospital stay and three severe subtypes associated with timely acute recovery. We confirmed that unresolved systemic inflammation and T-cell dysfunctions were hallmarks of increased severity and further distinguished patients with similar acute respiratory severity by their distinct immune profiles, which correlated with differences in demographic and clinical complications. Notably, one critical subtype (SubF) was uniquely characterized by early excessive inflammation, insufficient anticoagulation, and fatty acid dysregulation, alongside higher incidences of hematologic, cardiac, and renal complications, and an elevated risk of long COVID. Among the severe subtypes, significant differences in viral clearance and early antiviral responses were observed, with one subtype (SubC) showing strong early T-cell cytotoxicity but a poor humoral response, slower viral clearance, and greater risks of chronic organ dysfunction and long COVID. These findings provide crucial insights into the complex and context-dependent nature of COVID-19 immune responses, highlighting the importance of personalized therapeutic strategies to improve both acute and long-term outcomes.
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Details
- Title
- Unraveling SARS-CoV-2 Host-Response Heterogeneity through Longitudinal Molecular Subtyping
- Creators
- Kexin Wang - Yale UniversityYutong Nie - Yale UniversityCole Maguire - The University of Texas at AustinCaitlin Syphurs - Boston Children's HospitalHeejune Sheen - Yale UniversityMeagan Karoly - Boston Children's HospitalLinda Lapp - Prevention of Organ FailureJeremy P Gygi - Yale UniversityNaresh Doni Jayavelu - University of WashingtonRavi K Patel - University of California, San FranciscoAnnmarie Hoch - Boston Children's HospitalDavid Corry - Baylor College of MedicineFarrah Kheradmand - Baylor College of MedicineGrace A McComsey - University Hospitals of ClevelandAna Fernandez-Sesma - Icahn School of Medicine at Mount SinaiViviana Simon - Icahn School of Medicine at Mount SinaiJordan P Metcalf - University of Oklahoma Health Sciences CenterNelson I Agudelo Higuita - University of Oklahoma Health Sciences CenterWilliam B Messer - Oregon Health & Science UniversityMark M Davis - Stanford UniversityKari C Nadeau - Stanford UniversityMonica Kraft - University of ArizonaChris Bime - University of ArizonaJoanna Schaenman - University of California, Los AngelesDavid Erle - University of California, San FranciscoCarolyn S Calfee - University of California, San FranciscoMark A Atkinson - University of FloridaScott C Brackenridge - University of FloridaDavid A Hafler - Yale UniversityAlbert Shaw - Yale UniversityAdeeb Rahman - Immunai (United States)Catherine L Hough - Oregon Health & Science UniversityLinda N Geng - Stanford UniversityAl Ozonoff - Boston Children's HospitalElias K Haddad - Drexel UniversityElaine F Reed - University of California, Los AngelesHarm van Bakel - Icahn School of Medicine at Mount SinaiSeunghee Kim-Schultz - Icahn School of Medicine at Mount SinaiFlorian Krammer - Icahn School of Medicine at Mount SinaiMichael Wilson - University of California, San FranciscoWalter Eckalbar - University of California, San FranciscoSteven Bosinger - Emory UniversityCharles R Langelier - University of California, San FranciscoRafick P SekalyRuth R Montgomery - Yale UniversityHolden T Maecker - Stanford UniversityHarlan Krumholz - Yale UniversityEsther Melamed - The University of Texas at AustinHanno Steen - Boston Children's HospitalBali Pulendran - Palo Alto UniversityAlison D Augustine - National Institute of Allergy and Infectious DiseasesCharles B Cairns - Drexel UniversityNadine Rouphael - Emory UniversityPatrice M Becker - National Institute of Allergy and Infectious DiseasesSlim Fourati - Northwestern UniversityCasey P Shannon - Prevention of Organ FailureKinga K Smolen - Boston Children's HospitalBjoern Peters - La Jolla Institute for ImmunologySteven H Kleinstein - Yale UniversityOfer Levy - Broad InstituteMatthew C Altman - University of WashingtonAkiko Iwasaki - Yale UniversityJoann Diray-Arce - Boston Children's HospitalLauren I R Ehrlich - The University of Texas at AustinLeying Guan - Yale UniversityIMPACC Network
- Publication Details
- bioRxiv
- Publisher
- American Physical Society (APS); United States
- Resource Type
- Preprint
- Language
- English
- Academic Unit
- College of Medicine; Infectious Diseases (and HIV Medicine); Emergency Medicine
- Other Identifier
- 991021985402604721