Non-generalizability of biomarkers for mortality in SARS-CoV-2: a meta-analyses series

Rationale: Sophisticated prognostic scores have been proposed for SARS-CoV-2 but do not always perform consistently. We conducted these meta-analyses to uncover why and to investigate the impact of vaccination and variants. Methods: We searched the PubMed database for the keywords "SARS-CoV-2" with "biomarker" and "mortality" for the baseline tranche (01/12/2020-30/06/2021) and either "SARS-CoV-2" or "Covid19" with "biomarker" and either "vaccination" or "variant" from 01/12/2020 to 31/10/2023. To aggregate the data, the meta library in R was used, and a random effects model fitted to obtain pooled AUCs and 95% confidence intervals for the European/North American, Asian, and overall datasets. Results: Biomarker effectiveness varies significantly in different continents. Admission CRP levels were a good prognostic marker for mortality due to wild-type virus in Asian countries, with a pooled area under curve (AUC) of 0.83 (95%CI 0.80-0.85), but only an average predictor of mortality in Europe/North America, with a pooled AUC of 0.67 (95%CI 0.63-0.71, P<0.0001). We observed the same pattern for D-dimer and IL-6. This variability explains why the proposed prognostic scores did not perform evenly. Notably, urea and troponin had pooled AUCs [&ge;]0.78 regardless of location, implying that end-organ damage at presentation is a key prognostic factor. The inflammatory biomarkers (CRP, D-dimer and IL-6) have generally declined in effectiveness in the vaccinated and variant cohorts. We note a significant lag from the pandemic advent to data availability and this has no doubt impacted on patient care. Conclusions: Biomarker efficacies vary considerably by region. It is imperative that the infrastructure for collecting clinical data should be put in place ahead of a future pandemic.