Surfactant protein D (SP-D) as biomarker of SARSCOV-2 infection

ABSTRACT

Beside lowering the surface tension at air-liquid interface in the alveoli, the pulmonary surfactant has a pivotal role in triggering the elimination of pathogens or any hazardous materials introduced with breathing. Among the components of the pulmonary surfactant, surfactant protein-D (SP-D) is a low abundant (0.6%) hydrophilic protein that is able to promote pathogens clearance binding highly conserved glycosidic residues on their surface. SP-D also cooperates in the maintenance of lung homeostasis by directly modulating immune system activity. Previous investigations on acute respiratory distress syndrome (ARDS) patients demonstrated a significant increment of SP-D serum level compared with healthy donors. Since in physiological condition SP-D is not permeable to alveoli-capillary membrane and poorly express by other tissues, this enhancement is likely due to an impairment of the pulmonary barrier caused by prolonged inflammation. In view of the above, the present work aims to investigate SP-D as diagnostic and/or prognostic marker for COVID-19. In particular, a retrospective study on a relatively large cohort of patients of Hospital Pio XI of Desio (i.e., 79 mild cases plus 123 severe cases) was conducted to assess differences of the hematic levels of this biomarker among COVID-19 patients and healthy donors and if SP-D serum levels resulted a risk factor for disease severity and mortality. The performed analyses, using an Anova-Mixed model, showed a significant difference in the mean of log SP-D between COVID-19 patients and healthy donors 150 ng/mL was identified as threshold value to best discriminate the mentioned groups. Significant differences were also found between dead vs survived patients, as well among severe vs non-severe cases. In all cases, SP-D serum levels presented significantly higher values for COVID-19 patients, dead and severe cases.Moreover, further analysis conducted with Logistic Mixed models, highlighted that SP-D, in a model with Age, C-reactive protein and cancer status, resulted the strongest significant risk factor of mortality (model predictive accuracy, AUC=0.826), and in a lesser extent for risk of severity.The overall data suggest that SP-D can be a predictive marker of COVID-19 disease and its outcome.