Coronavirus disease 2019 subphenotypes and differential treatment response to convalescent plasma in critically ill adults: secondary analyses of a randomized clinical trial.

Adult Humans COVID-19 / therapy Critical Illness / therapy Biomarkers Cytokines Treatment Outcome COVID-19 Serotherapy

Convalescent plasma Precision medicine Subphenotypes

Journal

Intensive care medicine

ISSN: 1432-1238

Titre abrégé: Intensive Care Med

Pays: United States

ID NLM: 7704851

Informations de publication

Date de publication:
11 2022

Historique:

received: 12 07 2022

accepted: 11 08 2022

pubmed: 15 9 2022

medline: 27 10 2022

entrez: 14 9 2022

Statut: ppublish

Résumé

Benefit 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 . We 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) . Unsupervised 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). We 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.

Identifiants

DOI: 10.1007/s00134-022-06869-w PMID: 36102943 PMC: PMC9472738

pubmed: 36102943

doi: 10.1007/s00134-022-06869-w

pii: 10.1007/s00134-022-06869-w

pmc: PMC9472738

doi:

Substances chimiques

Biomarkers 0

Cytokines 0

Types de publication

Randomized Controlled Trial Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

1525-1538

Subventions

Organisme : National Institute for Health Research

ID : COV19-RECPLAS

Commentaires et corrections

Type : CommentIn

Informations de copyright

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