Colaneri, Marta

Background Bacterial infections remain a major global health burden, causing significant morbidity and mortality. Despite ongoing advances, prompt diagnosis is still hampered by nonspecific host biomarkers and the inherently slow turnaround of traditional microbiological cultures. These limitations often delay the initiation of appropriate treatments. In recent years, affinity-based proteomic approaches have been explored to address this gap. Among them, the Proximity Extension Assay (PEA) has emerged as a promising multiplexed protein quantification tool, capable of simultaneously measuring hundreds of immune and inflammatory proteins with high sensitivity from minimal sample volumes. Such technologies hold the potential to identify novel biomarkers, thereby improving both diagnosis and patient management in bacterial infections. Main body In this systematic scoping review, we examined studies applying PEA-based proteomics to adult bacterial infections. Out of the records screened, ten studies met inclusion criteria. Most were conducted in Europe and North America, relied primarily on plasma samples, and employed commercially available panels enriched for immune and inflammatory mediators. Study quality varied, with some evidence of variability and potential risk of bias. Across the 379 proteins investigated, a subset of proteins were consistently associated with bacterial infections across multiple clinical contexts, whereas others showed limited or no associations. Conclusions Current applications of PEA-based proteomics in adult bacterial infections is limited and largely exploratory. Rather than supporting immediate clinical translation, the available evidence suggests the value of PEA-based approaches for informing biomarker discovery. Future research should prioritize well-designed, longitudinal, and pathogen-stratified studies in clinically relevant settings to strengthen evidence robustness and support the rational development of proteomics-informed diagnostic and translational strategies.

Abstract Background Studies aiming to synthetize data from literature are helpful to valid the robustness of associations, to assess the quality of the data, and, eventually, to propose recommendations. This is particularly evident for the huge amount of data reported for SARS-CoV-2. The aim of this study was to perform an umbrella review to identify the strength and validity of associations between variants of concern (VOCs) and pre-specified clinical outcomes in COVID-19 patients. Table 1 Effect size measures reported in the studies included in the review, divided by outcome. Acronyms: CI, confidence interval; OR: odds ratio; RR, risk ratio; cCFR, confirmed case-fatality risk; HFR, hospitalization-fatality risk; N/A, not available Methods An umbrella review according to the principles to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was performed searching multiple databases in January 2024. Peer reviewed systematic reviews considering ≥ 2 VOCs with a clinical outcome among death, hospitalization, severe disease, admission to intensive care unit (ICU), and mechanical ventilation were included. Data on study population and measures of association between clinical outcome and VOCs were considered. The quality of the studies was assessed through the AMSTAR-2 tool. The effect size measures with the confidence interval for each association between VOCs and clinical outcomes were reported. Subgroup analyses were performed, if possible. A citation matrix was used to assess the overlap between the systematic reviews included. Table 2 Risk of bias assessment of the included systematic reviews using the AMSTAR-2 score. In bold the key domains. Results A total of 11 studies were included in our review. 24 total comparison were considered, most regarding Omicron versus Delta (19/24), where Omicron was always associated with better clinical outcomes than Delta. The overall quality of the studies was low. None of the reviewed studies incorporated consideration of risk factors other than VOCs in evaluating clinical outcomes. The overlap between the included reviews is low, only 10% of them having a significant overlap ( > 15%). Conclusion Our umbrella review shows the lower hazard on human health of the Omicron compared to Delta variant. However, the quality of the reviews included were generally low and there is a lack of correction with other risk factors such as comorbidities and vaccination status. While our review provides valuable insights into the association between VOCs and clinical outcomes of SARS-CoV-2 infection, further research incorporating risk factor analysis and ensuring methodological rigor is warranted. Disclosures All Authors: No reported disclosures