Clinical Utility of Circulating Pneumoproteins as Diagnostic and Prognostic Biomarkers in COVID-19: A Systematic Review and Meta-analysis

INTRODUCTION: This study explored circulating pneumoproteins in the diagnosis, severity, and prognosis of COVID-19 by meta-analysis. METHODS: We searched five databases and other sources until December 16, 2021. Standardized mean difference (SMD) and 95% confidence interval (CI) were the overall outcomes. RevMan 5.3, Stata 16, and Meta-DiSc 1.4 were utilized for pooled analysis. RESULTS: A total of 2432 subjects from 26 studies were included. Patients with COVID-19 had higher circulating KL-6, SP-D, and SP-A levels (SMD 1.34, 95% CI [0.60, 2.08]; SMD 1.74, 95% CI [0.64, 2.84]; SMD 3.42, 95% CI [1.31, 5.53], respectively) than healthy individuals. Circulating SP-D levels were not significantly different in survivors and non-survivors (SMD − 0.19, 95% CI [− 0.78, 0.40]). Circulating KL-6, SP-D, and RAGE levels in patients with mild to moderate COVID-19 were significantly lower (SMD − 0.93, 95% CI [− 1.22, − 0.65]; SMD − 1.32, 95% CI [− 2.34, − 0.29]; SMD − 1.17, 95% CI [− 2.06, − 0.28], respectively) than in patients with severe COVID-19. Subgroup analysis suggested that country and total number may be related to the heterogeneity when analyzing SP-D in patients with mild to moderate vs. severe COVID-19. The meta-analysis of diagnostic accuracy including KL-6 for severity, KL-6 for mortality, and SP-D for severity demonstrated that they all had limited diagnostic value. CONCLUSION: Therefore, circulating pneumoproteins (KL-6, SP-D, and RAGEs) reflect the diagnosis, severity, and prognosis of COVID-19, and follow-up studies are still needed. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40121-022-00686-w.