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 (I = 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).