ArticleCommunications medicine2026
Unbiased characterization of COVID-19 endotypes leads to prognostication of high-risk individuals using routine blood tests.
Article in Communications medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundOnly a subset of individuals infected with SARS‑CoV‑2 develop severe COVID‑19. Improved tools for early diagnosis and prognostication are needed. We hypothesized that unsupervised analysis of detailed circulating proteomes could reveal biologically meaningful patient endotypes and help identify individuals at elevated risk of severe outcomes.
methodsWe performed unsupervised stratification of the circulating proteome in 731 SARS‑CoV‑2 PCR‑positive participants from the Biobanque québécoise de la COVID‑19 (BQC19), representing a range of disease severities. We also developed a prognostic model based solely on clinical laboratory measurements and applied it to 903 patients recruited across early pandemic waves (2020-2022) to generalize identified endotypes.
resultsSix proteomic endotypes (EPs) emerged. Endotype EP6 showed the highest frequencies of ICU admission, ARDS, and mortality. EP6 was marked by elevated C‑reactive protein, D‑dimer, interleukin‑6, ferritin, soluble fms‑like tyrosine kinase‑1, increased neutrophils, and reduced lymphocyte counts. SHC4 emerged as a protein quantitative trait locus associated with EP6. Among EP6 patients requiring mechanical ventilation, we observed alterations in lipoprotein metabolism, and alpha‑L‑iduronidase levels inversely correlated with duration of ventilation.
conclusionsUnsupervised proteomic analysis identified biologically coherent endotypes that advance understanding of acute lung injury in COVID‑19 and support improved diagnostic and prognostic strategies.
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