Koc Suna, Senturk Kamil Cankut, Cetinkaya Sefa, Yenmis Guven, Arkan Hulya, Demirbilek Mahmut, Acar Pinar, Arikan Erhan, Dokur Mehmet
Department of Anesthesia and Reanimation, School of Medicine, Biruni University, Istanbul 34015, Turkey.
School of Medicine, Biruni University, Istanbul 34015, Turkey.
Diagnostics (Basel). 2025 Jul 2;15(13):1690. doi: 10.3390/diagnostics15131690.
Severe COVID-19 pneumonia damages alveolar type II cells and disrupts surfactant homeostasis, 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 for innate immune defense. We aimed to evaluate whether surfactant protein gene expression varies with the severity of COVID-19. Peripheral blood was collected from 122 adults with confirmed COVID-19, categorized as asymptomatic (no symptoms), mild (requiring hospitalization), or severe (requiring ICU admission). We quantified mRNA expression of surfactant protein genes (SFTPA1, SFTPA2, SFTPB, SFTPC, SFTPD) in blood cells using RT-qPCR. Relative expression was normalized to GAPDH and compared among the groups using the 2 method. Outliers (Ct values > 3 SD from the mean) were excluded before analysis. Distinct surfactant gene expression patterns were markedly associated with disease severity. Transcripts of SFTPB and SFTPC decreased with increasing severity of the disease. Notably, SFTPC expression was ~49-fold higher in mild cases compared to asymptomatic COVID-19-positive patients ( < 0.0001), but then decreased by ~54-fold in severe cases relative to mild ( < 0.0001), returning to near-baseline levels. In contrast, SFTPA2 and SFTPD were dramatically upregulated in severe cases. SFTPA2 was ~50-fold higher in severe versus mild cases ( < 0.0001), and SFTPD was ~4346-fold higher in severe versus asymptomatic cases ( < 0.0001; ~9.6-fold higher than in mild). SFTPA1 showed only a modest ~1.4-fold decrease in severe cases (vs. mild). All noted differences remained statistically significant after outlier exclusion. COVID-19 severity is correlated with profound changes in surfactant gene expression in blood. Critically ill patients exhibit loss of key surfactant components (SP-B and SP-C transcripts) alongside an excessive SP-D response. These preliminary findings suggest an imbalance that may contribute to lung injury in severe disease. However, further validation is needed to establish surfactant proteins, such as SP-D, as biomarkers of COVID-19 severity.
重症新型冠状病毒肺炎会损害Ⅱ型肺泡细胞并破坏表面活性剂稳态，进而导致急性呼吸窘迫综合征（ARDS）。表面活性剂蛋白（SP-A、SP-B、SP-C、SP-D）对于降低肺泡表面张力和固有免疫防御至关重要。我们旨在评估表面活性剂蛋白基因表达是否随新型冠状病毒肺炎的严重程度而变化。从122例确诊新型冠状病毒肺炎的成年人中采集外周血，这些患者分为无症状（无症状）、轻症（需要住院治疗）或重症（需要入住重症监护病房）。我们使用逆转录定量聚合酶链反应（RT-qPCR）对血细胞中表面活性剂蛋白基因（SFTPA1、SFTPA2、SFTPB、SFTPC、SFTPD）的mRNA表达进行定量。相对表达以甘油醛-3-磷酸脱氢酶（GAPDH）为标准进行归一化，并使用2-△△Ct方法在各组之间进行比较。在分析前排除异常值（Ct值高于平均值3个标准差）。不同的表面活性剂基因表达模式与疾病严重程度显著相关。SFTPB和SFTPC的转录本随疾病严重程度的增加而降低。值得注意的是，与无症状新型冠状病毒肺炎阳性患者相比，轻症病例中SFTPC的表达高约49倍（P<0.0001），但相对于轻症病例，重症病例中SFTPC的表达下降约54倍（P<0.0001），恢复到接近基线水平。相比之下，SFTPA2和SFTPD在重症病例中显著上调。与轻症病例相比，重症病例中SFTPA2高约50倍（P<0.0001），与无症状病例相比，重症病例中SFTPD高约4346倍（P<0.0001；比轻症病例高约9.6倍）。SFTPA1在重症病例中仅出现适度的约1.4倍下降（与轻症相比）。在排除异常值后，所有观察到的差异仍具有统计学意义。新型冠状病毒肺炎的严重程度与血液中表面活性剂基因表达的深刻变化相关。危重症患者表现出关键表面活性剂成分（SP-B和SP-C转录本）的缺失以及过度的SP-D反应。这些初步发现表明存在一种失衡，这可能导致重症疾病中的肺损伤。然而，需要进一步验证以确立表面活性剂蛋白，如SP-D，作为新型冠状病毒肺炎严重程度的生物标志物。
