Serum hydroxybutyrate dehydrogenase and COVID-19 severity and mortality: a systematic review and meta-analysis with
Angelo Zinellu1, Panagiotis Paliogiannis2, Ciriaco Carru1,2
1Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
Insights
Higher hydroxybutyrate dehydrogenase (HBDH) levels indicate increased cardiac and renal injury in COVID-19 patients. This biomarker may help stratify risk for severe disease and mortality.
Area of Science:
- Cardiology
- Nephrology
- Infectious Diseases
- Biomarker Research
Background:
- Coronavirus disease 19 (COVID-19) is associated with cardiac and renal complications.
- Hydroxybutyrate dehydrogenase (HBDH) is a biomarker reflecting myocardial and renal injury.
- Understanding HBDH levels in COVID-19 is crucial for assessing disease severity and prognosis.
Approach:
- Systematic review and meta-analysis of 22 studies involving 15,019 COVID-19 patients.
- Searched PubMed, Web of Science, and Scopus (December 2019 - April 2021).
- Assessed risk of bias, publication bias, and certainty of evidence using established methods.
Key Points:
- Serum HBDH concentrations were significantly higher in severe COVID-19 cases and non-survivors.
- Elevated HBDH levels correlated with markers of inflammation, sepsis, liver damage, and tissue injury.
- Sensitivity analyses confirmed the robustness of the findings despite high heterogeneity.
Conclusions:
- Higher HBDH concentrations are linked to increased COVID-19 severity and mortality.
- HBDH shows potential as a valuable biomarker for risk stratification in COVID-19 patients.
- Further research can explore HBDH's role in managing COVID-19 related organ damage.
Abstract:
Alterations in cardiac and renal biomarkers have been reported in coronavirus disease 19 (COVID-19). We conducted a systematic review and meta-analysis to investigate serum concentrations of hydroxybutyrate dehydrogenase (HBDH), a combined marker of myocardial and renal injury, in hospitalized COVID-19 patients with different disease severity and survival status. We searched PubMed, Web of Science and Scopus, between December 2019 and April 2021, for studies reporting HBDH in COVID-19. Risk of bias was assessed using the Newcastle-Ottawa scale, publication bias was assessed with the Begg's and Egger's tests, and certainty of evidence was assessed using GRADE. In 22 studies in 15,019 COVID-19 patients, serum HBDH concentrations on admission were significantly higher in patients with high disease severity or non-survivor status when compared to patients with low severity or survivor status (standardized mean difference, SMD = 0.90, 95% CI 0.74 to 1.07, p < 0.001; moderate certainty of evidence). Extreme between-study heterogeneity was observed (I2 = 93.5%, p < 0.001). Sensitivity analysis, performed by sequentially removing each study and re-assessing the pooled estimates, showed that the magnitude and the direction of the effect size were not substantially modified. A significant publication bias was observed. In meta-regression, the SMD of HBDH concentrations was significantly associated with markers of inflammation, sepsis, liver damage, non-specific tissue damage, myocardial injury, and renal function. Higher HBDH concentrations were significantly associated with higher COVID-19 severity and mortality. This biomarker of cardiac and renal injury might be useful for risk stratification in COVID-19. (PROSPERO registration number: CRD42021258123).
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