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The following is a summary of “Immunological sub-phenotypes and response to convalescent plasma in COVID-19 induced ARDS: a secondary analysis of the CONFIDENT trial,” published in the October 2024 issue of Critical Care by Misset et al.

Researchers conducted a retrospective study to examine the patient clusters, defined by immunological heterogeneity, differentially respond to convalescent plasma (CP) therapy in COVID-19-induced acute respiratory distress syndrome (C-ARDS).  

They measured 20 cytokines, chemokines, and cell adhesion markers using a multiplex technique at the time of inclusion in the CONFIDENT trial in patients from centers that agreed to participate in this secondary study. Descriptive statistics and unsupervised hierarchical cluster analysis were performed, and the association between the clusters and the impact of CP on day-28 mortality was examined.  

The results showed from 475 patients in the CONFIDENT trial, 391 (82%) were sampled, and 196 (50.1%) were assigned to CP, 4 sub-phenotypes were identified, representing 89 (22.8%), 178 (45.5%), 38 (9.7%), and 86 (22.0%) patients, respectively. The principal component analysis revealed that the most influential biomarkers were IL-1β, IL-12p70, IL-6, IFN-α, IL-17A, IFN-γ, IL-13, TFN-α, total IgG, and CXCL10. Sub-phenotype-1 showed a lower immune response, sub-phenotype-2 exhibited a higher adaptive response, sub-phenotype-3 had the highest innate antiviral, pro- and anti-inflammatory response, along with adhesion molecule activation, and sub-phenotype-4 demonstrated a higher pro- and anti-inflammatory response, migration protein, and adhesion molecule activation. Sub-phenotypes 2 and 4 showed higher severity at the time of inclusion. The CP treatment appeared to reduce mortality more than standard care in all sub-phenotypes, with no significant heterogeneity observed between sub-phenotypes (P = 0.97).  

Investigators concluded 4 distinct sub-phenotypes of C-ARDS were identified based on immune response profiles, each associated with specific clinical characteristics. However, the efficacy of CP therapy was consistent across all sub-phenotypes. 

Source: annalsofintensivecare.springeropen.com/articles/10.1186/s13613-024-01392-1