Prognostic value of elevated lactate dehydrogenase in patients with COVID-19: a systematic review and meta-analysis

Januar Wibawa Martha, Arief Wibowo, Raymond Pranata, Januar Wibawa Martha, Arief Wibowo, Raymond Pranata

Abstract

Purpose: This meta-analysis aimed to evaluate the prognostic performance of elevated lactate dehydrogenase (LDH) in patients with COVID-19.

Methods: A systematic literature search was performed using PubMed, Embase and EuropePMC on 19 November 2020. The outcome of interest was composite poor outcome, defined as a combined endpoint of mortality, severity, need for invasive mechanical ventilation and need for intensive care unit care. Severity followed the included studies' criteria.

Results: There are 10 399 patients from 21 studies. Elevated LDH was present in 44% (34%-53%) of the patients. Meta-regression analysis showed that diabetes was correlated with elevated LDH (OR 1.01 (95% CI 1.00 to 1.02), p=0.038), but not age (p=0.710), male (p=0.068) and hypertension (p=0.969). Meta-analysis showed that elevated LDH was associated with composite poor outcome (OR 5.33 (95% CI 3.90 to 7.31), p<0.001; I2: 77.5%). Subgroup analysis showed that elevated LDH increased mortality (OR 4.22 (95% CI 2.49 to 7.14), p<0.001; I2: 89%). Elevated LDH has a sensitivity of 0.74 (95% CI 0.60 to 0.85), specificity of 0.69 (95% CI 0.58 to 0.78), positive likelihood ratio of 2.4 (95% CI 1.9 to 2.9), negative likelihood ratio of 0.38 (95% CI 0.26 to 0.55), diagnostic OR of 6 (95% CI 4 to 9) and area under curve of 0.77 (95% CI 0.73 to 0.80). Elevated LDH would indicate a 44% posterior probability and non-elevated LDH would in indicate 11% posterior probability for poor prognosis. Meta-regression analysis showed that age, male, hypertension and diabetes did not contribute to the heterogeneity of the analyses.

Conclusion: LDH was associated with poor prognosis in patients with COVID-19.

Prospero registration number: CRD42020221594.

Keywords: COVID-19; adult intensive & critical care; intensive & critical care.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
PRISMA flow chart. LDH, lactate dehydrogenase; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
Figure 2
Figure 2
Forest-plot for lactate dehydrogenase and composite poor outcome. LDH, lactate dehydrogenase.
Figure 3
Figure 3
Pooled sensitivity and specificity. LDH, lactate dehydrogenase.
Figure 4
Figure 4
Summary receiver operating characteristics (SROC) curve . AUC, area under curve; SROC, summary receiver operating characteristic
Figure 5
Figure 5
Fagan’s normogram. LR, likelihood ratio.
Figure 6
Figure 6
Univariable meta-regression and subgroup analyses.

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