Serum hydroxybutyrate dehydrogenase and COVID-19 severity and mortality: a systematic review and meta-analysis with meta-regression

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).