Surfactant protein levels and genetic variants as biomarkers for COVID-19 severity in children.

Abstract

Since its outbreak, the novel coronavirus (COVID-19) has significantly impacted the pediatric population. Pulmonary surfactant dysfunction has been linked to other respiratory diseases in children and COVID-19 in adults, but its role in COVID-19 severity remains unclear. We hypothesized that elevated surfactant protein (SP) levels and single nucleotide polymorphisms (SNPs) of SP genes are associated with severe COVID-19 in children. We enrolled 325 COVID-19 positive children and categorized them as having mild or severe disease. Plasma SP-A, SP-B, and SP-D levels were measured. DNA was extracted and genotyped for SNPs in five SP genes, SFTPA1, SFTPA2, SFTPB, SFTPC, and SFTPD. Quantile regression was used to compare SP levels between groups, and receiver operating curve analysis determined an optimal cutoff value of SP level for predicting severe COVID-19. Logistic regression evaluated the odds ratio (OR) for severe disease and associations between SNPs and COVID-19 severity. We found that increased plasma SP-A levels, but not SP-B or SP-D, were significantly associated with severe COVID-19. No significant correlation was observed between age and SP levels. A plasma SP-A level of 10 ng/mL was identified as the optimal cutoff for predicting severe COVID-19, with an OR of 5.9, indicating that children with SP-A levels above this threshold are nearly six times more likely to develop severe COVID-19 disease. Additionally, the rs8192340 of SFTPC was associated with decreased risk of severe COVID-19 before, but not after, Bonferroni correction. These findings suggest that plasma SP-A may serve as a potential biomarker for severe COVID-19 in children.