Proteome signatures in ICU patients with COVID-19 and acute brain dysfunction: an observational cohort study

Abstract

Abstract Deep sedation and delirium are common in COVID-19 intensive care unit (ICU) patients. Biomarkers for prediction, detection, and monitoring are missing. Unbiased omics analyses are warranted to gain a systems biology view on pathophysiology. This prospective observational satellite study analysed the proteome signatures of COVID-19 ICU patients with and without acute brain dysfunction (ABD). Conducted in university hospital ICUs between March 2020 and September 2021, patients of legal age with a positive SARS-CoV-2 test were screened daily for deep sedation and delirium. Blood samples were taken thrice weekly. In total, 457 samples were analysed using data-independent acquisition mass spectrometry to determine protein levels. A mixed-effects regression model was developed to identify proteins significantly influenced by ABD, accounting for sex, age and illness severity as confounders. This model also aimed to determine proteins that were either up- or downregulated in association with ABD. Additionally, an enrichment analysis was conducted to examine the biological pathways linked to these ABD-associated proteins. Among 360 patients, 69 were analysed for protein profiling; 42 (60.9%) had ABD at ICU admission [deep sedation: (33; 47,8%); delirium (9; 13%)]. Of 204 proteins, deep sedation markedly shaped the proteomic profile, with 23 proteins uniquely distinguishing it from delirium and no ABD, and 21 proteins were shared across both ABD states. Four proteins (SERPINF1, C1QB, C1QC, PPBP) were specific to delirium, while three (GSN, C1S, PON1) differed across all groups. APOC3 displayed a distinct gradient, highest in delirium and lowest in deep sedation. Pathways involved coagulation, immune response, and lipid metabolism: deep sedation was characterized by complement and coagulation signatures, whereas delirium was also linked to lipid-related processes. The enrichment pathway analysis revealed “Network map of SARS-CoV-2 signalling” (M42569/WP5115) in deep sedation, and “Homeostatic process” (M17351) in delirium. We identified proteomic signatures in COVID-19 ICU patients with ABD, including up- and downregulated proteins. These findings may provide potential biomarker candidates for the assessment of ABD risk and its underlying causes. They could represent a further step towards the development of personalized, causative treatments for delirium and its monitoring in the ICU. Trial registration: The study was retrospectively registered in the German Clinical Trials Register (DRKS00021688 May 13, 2020).

The authors' abstract, as published at the source. Scientific Reports, 2026 · DOI ↗