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Immune dysregulation through longitudinal lymphocyte trajectories and their clinical determinants in hospitalized COVID-19 patients

2026Artigo científico Acesso aberto
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dc.contributor.authorthe ISARIC Characterization Group
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.institutionComprehensive Health Research Centre (CHRC) - pólo NMS
dc.contributor.pblEuropean Society of Intensive Care Medicine (ESICM) | SpringerOpen
dc.date.accessioned2026-03-31T13:21:01Z
dc.date.available2026-03-31T13:21:01Z
dc.date.issued2026
dc.descriptionPublisher Copyright: © The Author(s) 2026.
dc.description.abstractObjective: Immune dysregulation plays a pivotal role in the pathophysiology of sepsis and COVID-19, with lymphopenia emerging as a consistent marker of severity and poor prognosis. However, most existing studies have assessed lymphocyte counts at isolated time points, limiting insights into their temporal behavior and prognostic value. The dynamics of lymphocyte recovery or persistence of lymphopenia remain largely unexplored in large populations, as well as the impact of adjunctive therapies such as corticosteroids. We hypothesized that the persistence or recovery of lymphopenia may be key to understanding disease progression and predicting outcomes. Using the multinational ISARIC cohort, we investigated longitudinal lymphocyte trajectories in hospitalized patients and the clinical determinants associated with their evolution over time. Methods: We conducted a multinational prospective observational cohort study using data from the ISARIC-WHO Clinical Characterization Protocol. Patients with confirmed SARS-CoV-2 infection and at least four lymphocyte measurements during the first 28 days of hospitalization were included. We analyzed lymphocyte trajectories, Cox regression survival analyses and multivariable linear regression modelling. We also applied multistate models and joint modeling to assess the association between lymphocyte trajectories and 28-day mortality, incorporating corticosteroid use as a time-varying covariate. Results: Of 945,317 screened patients, 231,933 hospitalized adults with confirmed COVID-19 and sufficient lymphocyte data were included, with 56.6% classified as lymphopenic. Lymphopenia was independently associated with higher rates of ICU admission, organ support, and in-hospital mortality (OR = 1.52, 95% CI 1.48–1.55), and lower absolute lymphocyte counts were strongly linked to worse survival in adjusted Cox models (HR = 1.33 per 1 × 10⁹ cells/L decrease, 95% CI 1.28–1.38). Multistate modeling revealed that lymphopenic patients had a significantly higher daily transition rate to death and a shorter duration in that immune state, while corticosteroid exposure was associated with an increased likelihood of entering and remaining in lymphopenia. Joint modeling identified age, sex, and corticosteroid use as significant predictors of lower lymphocyte trajectories over time, with distinct dynamics between survivors and non-survivors. Conclusion: Lymphopenia was common and strongly associated with worse outcomes in hospitalized COVID-19 patients, with impaired recovery particularly evident in those receiving corticosteroids. These findings highlight the value of lymphocyte monitoring to inform tailored immunomodulatory strategies in sepsis and severe viral infections.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent1510484
dc.identifier.doi10.1186/s40635-026-00864-x
dc.identifier.issn2197-425X
dc.identifier.otherPURE: 157625928
dc.identifier.otherPURE UUID: 5ef1e653-c1e5-455e-923f-aeb6b652ab07
dc.identifier.otherScopus: 105032104823
dc.identifier.urihttp://hdl.handle.net/10362/201958
dc.identifier.urlhttps://www.scopus.com/pages/publications/105032104823
dc.language.isoeng
dc.peerreviewedyes
dc.subjectCorticosteroids
dc.subjectCOVID-19
dc.subjectImmunity
dc.subjectIn-hospital mortality
dc.subjectLymphopenia
dc.subjectMultistate analysis
dc.subjectSepsis
dc.subjectEmergency Medicine
dc.subjectCritical Care and Intensive Care Medicine
dc.subjectPhysiology (medical)
dc.titleImmune dysregulation through longitudinal lymphocyte trajectories and their clinical determinants in hospitalized COVID-19 patientsen
dc.typejournal article
degois.publication.issue1
degois.publication.titleIntensive Care Medicine Experimental
degois.publication.volume14
dspace.entity.typePublication
rcaap.rightsopenAccess

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