| Autor: |
Wang K, Nie Y, Maguire C, Syphurs C, Sheen H, Karoly M, Lapp L, Gygi JP, Jayavelu ND, Patel RK, Hoch A, Corry D, Kheradmand F, McComsey GA, Fernandez-Sesma A, Simon V, Metcalf JP, Higuita NIA, Messer WB, Davis MM, Nadeau KC, Kraft M, Bime C, Schaenman J, Erle D, Calfee CS, Atkinson MA, Brackenridge SC, Hafler DA, Shaw A, Rahman A, Hough CL, Geng LN, Ozonoff A, Haddad EK, Reed EF, van Bakel H, Kim-Schultz S, Krammer F, Wilson M, Eckalbar W, Bosinger S, Langelier CR, Sekaly RP, Montgomery RR, Maecker HT, Krumholz H, Melamed E, Steen H, Pulendran B, Augustine AD, Cairns CB, Rouphael N, Becker PM, Fourati S, Shannon CP, Smolen KK, Peters B, Kleinstein SH, Levy O, Altman MC, Iwasaki A, Diray-Arce J, Ehrlich LIR, Guan L |
| Jazyk: |
angličtina |
| Zdroj: |
BioRxiv : the preprint server for biology [bioRxiv] 2024 Nov 25. Date of Electronic Publication: 2024 Nov 25. |
| DOI: |
10.1101/2024.11.22.624784 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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