The complexity of examining laboratory based biological markers associated with mortality in hospitalized patients during early phase of the COVID-19 pandemic: A systematic review and evidence map

Lauren E. Griffith, Muhammad Usman Ali, Alessandra Andreacchi, Mark Loeb, Meghan Kenny, Divya Joshi, Vishal Mokashi, Ahmed Irshad, Angela K. Ulrich, Nicole E Basta, Parminder Raina, Laura Anderson, Cynthia Balion

Research output: Contribution to journalArticlepeer-review

Abstract

Importance The measurement of laboratory biomarkers plays a critical role in managing patients with COVID-19. However, to date most systematic reviews examining the association between laboratory biomarkers and mortality in hospitalized patients early in the pandemic focused on small sets of biomarkers, did not account for multiple studies including patients within the same institutions during overlapping timeframes, and did not include a significant number of studies conducted in countries other than China. Objective To provide a comprehensive summary and an evidence map examining the relationship between a wide range of laboratory biomarkers and mortality among patients hospitalized with COVID-19 during the early phase of the pandemic in multiple countries. Evidence review MEDLINE, EMBASE, and Web of Science were searched from Dec 2019 to March 9, 2021. A total of 14,049 studies were identified and screened independently by two raters; data was extracted by a single rater and verified by a second. Quality was assessed using the Joanna Briggs Institute (JBI) Case Series Critical Appraisal tool. To allow comparison across biomarkers, standardized mean differences (SMD) were used to quantify the relationship between laboratory biomarkers and hospital mortality. Meta-regression was conducted to account for clustering within institutions and countries. Results Our systematic review included 94 case-series studies from 30 countries. Across all biomarkers, the largest and most precise SMDs were observed for cardiac (troponin (1.03 (95% CI 0.86 to 1.21)), and BNP/NT-proBNP (0.93 (0.52 to 1.34)), inflammatory (IL-6 (0.97 (0.67 to 1.28) and Neutrophil-to-lymphocyte ratio (0.94 (0.59 to 1.29)), and renal biomarkers (blood urea nitrogen (1.01 (0.79 to 1.23)) and estimated glomerular filtration rate (-0.96 (-1.42 to -0.50)). There was heterogeneity for most biomarkers across countries with studies conducted in China generally having larger effect sizes. Conclusions and relevance The results of this study provide an early pandemic summary of the relationship between biomarkers and mortality in hospitalized patients. We found our estimated ESs were generally attenuated compared to previous systematic reviews which predominantly included studies conducted in China. Despite using sophisticated methodology to examine studies across countries, heterogeneity in reporting of case-series studies early in the pandemic limits clinical interpretability.

Original languageEnglish (US)
Article numbere0273578
JournalPloS one
Volume17
Issue number9
DOIs
StatePublished - Sep 2022

Bibliographical note

Publisher Copyright:
© 2022 Griffith et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Keywords

  • Biomarkers
  • COVID-19/epidemiology
  • Hospital Mortality
  • Hospitalization
  • Humans
  • Pandemics

PubMed: MeSH publication types

  • Journal Article
  • Systematic Review

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