Cystatin C, COVID-19 severity and mortality: a systematic review and meta-analysis

Background: Combined markers of renal dysfunction and inflammation, e.g., cystatin C, might assist with risk stratification and clinical decisions in patients with coronavirus disease 19 (COVID-19). We conducted a systematic review and meta-analysis with meta-regression of serum cystatin C in COVID-19. Methods: We searched PubMed, Web of Science and Scopus, between January 2020 and February 2021, for studies reporting serum cystatin C concentrations, measures of clinical severity and survival outcomes in hospitalized COVID-19 patients (PROSPERO registration number: CRD42021245295). Results: Thirteen studies in 2510 COVID-19 patients, 1972 with low severity or survivor status and 538 with high severity or non-survivor status during follow up, were included in the meta-analysis. The pooled results showed that serum cystatin C concentrations were higher in patients with high disease severity or non-survivor status (standard mean deviation, SMD, 1.71, 95% CI 0.95 to 2.46, p < 0.001). Extreme between-study heterogeneity was observed (I² = 97.5%, p < 0.001). Sensitivity analysis, performed by sequentially removing each study and re-assessing the pooled estimates, showed that the magnitude and direction of the effect size was not substantially modified. The Begg’s and Egger’s t tests did not show publication bias. In meta-regression, the SMD of serum cystatin C was not associated with age, proportion of males, C-reactive protein, neutrophils, lymphocytes, aspartate aminotransferase, alanine aminotransferase, albumin, creatinine, creatine kinase-MB, lactate dehydrogenase, and proportion of patients with diabetes or hypertension. Conclusions: Higher concentrations of serum cystatin C were associated with higher COVID-19 severity and mortality. Graphic abstract: [Figure not available: see fulltext.]