Serum amyloid A concentrations, COVID-19 severity and mortality: an updated systematic review and meta-analysis

BACKGROUND AND OBJECTIVES: An excessive inflammatory response in patients with coronavirus disease 2019 (COVID-19) is associated with high disease severity and mortality. Specific acute phase reactants might be useful for risk stratification. We conducted a systematic review and meta-analysis of studies of serum amyloid A (SAA) in patients with COVID-19.METHODS: We searched PubMed, Web of Science and Scopus, between January 2020 and December 2020, for studies reporting SAA concentrations, COVID-19 severity and survival status.RESULTS: Nineteen studies in 5,617 COVID-19 patients were included in the meta-analysis. Pooled results showed that SAA concentrations were significantly higher in patients with severe disease and non-survivors (standard mean difference, SMD, 1.20, 95% CI 0.91-1.49, P<0.001). Extreme between-study heterogeneity was observed (I2=92.4%, P<0.001). In sensitivity analysis, the effect size was not significantly affected when each study was in turn removed (range between 1.10-1.29). The Begg's (P=0.030), but not the Egger's (P=0.385), test revealed the presence of publication bias. Pooled SMD values were significantly and positively associated with gender (t=2.20, P=0.047) and aspartate aminotransferase (t=3.44, P=0.014).CONCLUSIONS: SAA concentrations were significantly and positively associated with higher COVID-19 severity and mortality. This acute phase reactant might assist with risk stratification and monitoring in this group.