ArticleIntensive care medicine2022
Coronavirus disease 2019 subphenotypes and differential treatment response to convalescent plasma in critically ill adults: secondary analyses of a randomized clinical trial.
Article in Intensive care medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Sepsis subtypes and differential treatment response to vitamin C: biological sub-study of the LOVIT trial.Intensive care medicine · 2025Trial
- Evaluating plasma ferritin and suPAR as treatable traits for critically ill patients with COVID-19 treated with anakinra: an exploratory analysis of the immune modulation domain of the REMAP-CAP randomised clinical trial.Critical care (London, England) · 2026Observational
- A Clinical Predictor of Lung Molecular Endotype Identifies Heterogeneity in Corticosteroid Response in Severe COVID-19: an Emulated Target Trial.medRxiv : the preprint server for health sciences · 2026Article
- Artificial Intelligence- and Machine Learning-Assisted Subphenotyping for Personalized Immunotherapy in Sepsis.Journal of personalized medicine · 2026Review
- Sepsis subphenotypes, theragnostics and personalized sepsis care.Intensive care medicine · 2025Review
- Identifying biomarker-driven subphenotypes of cardiogenic shock: analysis of prospective cohorts and randomized controlled trials.EClinicalMedicine · 2025Article
- Immunological sub-phenotypes and response to convalescent plasma in COVID-19 induced ARDS: a secondary analysis of the CONFIDENT trial.Annals of intensive care · 2024Article
- Article
- Passive antibody therapy in emerging infectious diseases.Frontiers of medicine · 2023Review
- Clinical Sepsis Phenotypes in Critically Ill Patients.Microorganisms · 2023Review
- Thrombotic and hemorrhagic complications of COVID-19 in adults hospitalized in high-income countries compared with those in adults hospitalized in low- and middle-income countries in an international registry.Research and practice in thrombosis and haemostasis · 2023Article
- Identification of Distinct Clinical Phenotypes of Critically Ill COVID-19 Patients: Results from a Cohort Observational Study.Journal of clinical medicine · 2023Article
- Causal Bayesian machine learning to assess treatment effect heterogeneity by dexamethasone dose for patients with COVID-19 and severe hypoxemia.Scientific reports · 2023Article
- Medical Nutrition Therapy in Critically Ill Patients with COVID-19-A Single-Center Observational Study.Nutrients · 2023Observational
- Personalized medicine in COVID-19.Intensive care medicine · 2022Article
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Authors and funding
27 authors at 12 institutions in 1 country.
Funding
Abstract
purposeBenefit from convalescent plasma therapy for coronavirus disease 2019 (COVID-19) has been inconsistent in randomized clinical trials (RCTs) involving critically ill patients. As COVID-19 patients are immunologically heterogeneous, we hypothesized that immunologically similar COVID-19 subphenotypes may differ in their treatment responses to convalescent plasma and explain inconsistent findings between RCTs .
methodsWe tested this hypothesis in a substudy involving 1239 patients, by measuring 26 biomarkers (cytokines, chemokines, endothelial biomarkers) within the randomized, embedded, multifactorial, adaptive platform trial for community-acquired pneumonia (REMAP-CAP) that assigned 2097 critically ill COVID-19 patients to either high-titer convalescent plasma or usual care. Primary outcome was organ support free days at 21 days (OSFD-21) .
resultsUnsupervised analyses identified three subphenotypes/endotypes. In contrast to the more homogeneous subphenotype-2 (N = 128 patients, 10.3%; with elevated type i and type ii effector immune responses) and subphenotype-3 (N = 241, 19.5%; with exaggerated inflammation), the subphenotype-1 had variable biomarker patterns (N = 870 patients, 70.2%). Subphenotypes-2, and -3 had worse outcomes, and subphenotype-1 had better outcomes with convalescent plasma therapy compared with usual care (median (IQR). OSFD-21 in convalescent plasma vs usual care was 0 (- 1, 21) vs 10 (- 1, to 21) in subphenotype-2; 1.5 (- 1, 21) vs 12 (- 1, to 21) in suphenotype-3, and 0 (- 1, 21) vs 0 (- 1, to 21) in subphenotype-1 (test for between-subphenotype differences in treatment effects p = 0.008).
conclusionsWe reported three COVID-19 subphenotypes, among critically ill adults, with differential treatment effects to ABO-compatible convalescent plasma therapy. Differences in subphenotype prevalence between RCT populations probably explain inconsistent results with COVID-19 immunotherapies.
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