Altered Surfactant Protein Gene Expression in Peripheral Blood Is Associated with COVID-19 Disease Severity

Background/Objectives: Severe COVID-19 pneumonia causes alveolar type II cell damage and surfactant dysfunction, contributing to acute respiratory distress syndrome (ARDS). Surfactant proteins (SP-A, SP-B, SP-C, SP-D) are critical for reducing alveolar surface tension and defending against infection. We aimed to evaluate how surfactant protein gene expression affects COVID-19 severity Methods: Peripheral blood was collected from 122 adults with confirmed COVID-19, categorized as asymptomatic (no symptoms), mild (hospitalized), or severe (ICU admission). We quantified mRNA expression of surfactant protein genes (SFTPA1, SFTPA2, SFTPB, SFTPC, SFTPD) by RT-qPCR and compared relative expression levels between groups. Results: Surfactant gene expression patterns differed markedly with disease severity. SFTPB and SFTPC transcripts decreased as severity increased. Notably, SFTPC was ~49-fold higher in mild cases than asymptomatic controls, but then dropped ~54-fold in severe cases relative to mild, returning to near-baseline levels. In contrast, SFTPA2 and SFTPD were dramatically upregulated in severe illness. SFTPD expression in severe patients was ~4346-fold higher than in asymptomatic individuals (and ~9.6-fold higher than in mild cases). SFTPA2 was ~50-fold higher in severe versus mild cases. By comparison, SFTPA1 showed a modest ~1.4-fold decrease in severe cases (vs. mild). All noted differences were statistically significant (p < 0.05). Conclusion: COVID-19 severity is associated with distinct surfactant gene expression changes. Critically ill patients exhibited loss of key surfactant components (SP-B and SP-C) alongside an excessive SP-D response. This imbalance in the surfactant system likely contributes to alveolar collapse in severe COVID-19, and elevated SP-D may serve as a biomarker of lung injury severity.