A PTX3/LDH/CRP signature correlates with lung injury CTs scan severity and disease progression in paucisymptomatic COVID-19

Folci, M.; Brunetta, E.; Lanza, E.; Bottazzi, B.; Protti, A.; Messana, G.; Lisi, C.; Leone, R.; Sironi, M.; Generali, E.; Rodolfi, S.; Sagasta, M.; Voza, A.; Ciccarelli, M.; Garlanda, C.; Balzarini, L.; Mantovani, A.; Cecconi, M.; Force, Humanitas COVID-19 Task

Background Quantitative CT (QCT) analysis is an invaluable diagnostic tool to assess lung injury and predict prognosis of patients affected by COVID-19 pneumonia. PTX3 was recently described as one of the most reliable serological predictors of clinical deterioration and short-term mortality. The present study was designed to evaluate a correlation between serological biomarkers of inflammation and lung injury measured by QCT. Methods This retrospective monocentric study analysed a cohort of patients diagnosed with COVID-19 and admitted because of respiratory failure, or significant radiological involvement on chest CT scan. All patients, males and non-pregnant females older than 18 years, underwent chest CT scan and laboratory testing at admission. Exclusion criteria were defined by concurrent acute pathological processes and ongoing specific treatments which could interfere with immune activity. The cohort was stratified based on severity in mild and severe forms. Compromised lung at QCT was then correlated to serological biomarkers representative of Sars-CoV-2. We further developed a multivariable logistic model to predict CT data and clinical deterioration based on a specific molecular signature. Internal cross-validation led to evaluate discrimination, calibration, and clinical utility of the tool that was provided by a score to simplify its application. Findings 592 patients were recruited between March 19th and December 1st, 2020. Applying exclusion criteria which consider confounders, the cohort resulted in 366 individuals characterized by 177 mild and 189 severe forms. In our predictive model, blood levels of PTX3, CRP and LDH were found to correlate with QCT values in mild COVID-19 disease. A signature of these three biomarkers had a high predictive accuracy in detecting compromised lungs as assessed by QCT. The score was elaborated and resulted representative of lung CT damage leading to clinical deterioration and oxygen need in mild disease. Interpretation The LDH, PTX3, CRP blood signature can serve as a strong correlate of compromised lung in COVID-19, possibly integrating cellular damage, systemic inflammation, myeloid and endothelial cell activation.