Plasma and Airway Levels of Surfactant Protein D Degradation Reflect Progression of ARDS in Ventilated Patients with SARS-CoV-2

ABSTRACT

Background: Patients with COVID-19 present severe respiratory symptoms progressing to acute respiratory distress syndrome (ARDS). Upon infection, SARS-CoV-2 destroys cells expressing the ACE2 receptor including alveolar type II cells (AT2). These cells are found in the alveolar-capillary barrier which normally secrete pulmonary surfactant, a complex of lipid and surfactant proteins (SPA, SP-B, SP-C, SP-D). Exogenous surfactant therapy (mainly composed of phospholipids, SP-B, and SP-C) has been successful in treating neonatal respiratory distress syndrome (nRDS) caused by surfactant deficiency in preterm babies.Plasma SP-D has been proposed as a marker of lung injury in COVID-19 but so far, no reports have evaluated sequential SP-D levels in both airway and plasma. As part of a clinical trial repurposing surfactant therapy to treat adult ventilated COVID-19 patients, we hypothesized that plasma SP-D levels may reflect decreased lung integrity and that SP-D degradation in plasma and airway samples from COVID-19 patients may reflect disease progression and severity. Methods: Enzyme-linked immunosorbent assay (ELISA) was used to quantify SP-D concentration in patient plasma and tracheal aspirate samples. Western Blotting was used to identify any protein degradation. Sequential daily plasma and airway samples were analysed. Results: SP-D concentration in serum was 10-20 times higher in patients ventilated for COVID-19 than in healthy volunteers. Additionally, the concentration of SP-D in plasma has shown to be 10-100-fold higher than in tracheal aspirates. Furthermore, degraded fragments of SP-D were detected at a higher ratio than intact SP-D in plasma of ventilated patients. This ratio decreased with administration of surfactant therapy (containing phospholipids and SP-B and SP-C but no SPA or SP-D). Conclusions: Increased serum SP-D and decreased tracheal aspirate SP-D from ventilated COVID-19 patients suggested leakage of pulmonary surfactant into the bloodstream caused by damage to the alveolar-capillary barrier in diseased lungs. The ratio of degraded vs. intact SP-D found in the plasma was compared before and after therapeutic surfactant administration. The results indicated that levels of SP-D in plasma and tracheal aspirates together with the ratio of degraded and intact SP-D in the plasma may be useful indicators of the severity of COVID-19 lung disease progression.