Tracking the evolution of biomarker efficacy in SARS-CoV-2: a global meta-analyses series

Background: Sophisticated prognostic scores have been proposed for SARS-CoV-2 but do not always perform consistently. We performed this systematic review to discover why and to investigate the impact of vaccination and viral variants. Methods: We searched the PubMed database for the keywords ‘SARS-CoV-2’ or ‘Covid19’ 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. Results: We screened 4,688 potential source manuscripts and included 144 in the final analyses. Biomarker effectiveness varies significantly by geographical region. 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/Northern America, with a pooled AUC of 0.67 (95%CI 0.63-0.71, P<0.0001). The same pattern applies to D-dimer and IL-6. Notably, urea and troponin had pooled AUCs ≥0.78 regardless of location, implying that end-organ damage at presentation was a key prognostic factor in wild-type SARS-CoV-2 infection. 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 that the type of data varied considerably between studies. Conclusion: Biomarkers and prognostic scores should be tailored to populations. It is imperative that the infrastructure for collecting clinical data should be put in place ahead of a future pandemic so that data harvesting, collation and analysis can occur in a robust and timely manner to aid clinical decision making. Registration: This study was registered with PROSPERO (CRD42022366893).