Adjusting D-dimer to lung disease extent to exclude pulmonary embolism in COVID-19 patients (Co-LEAD)

ABSTRACT

Background: D-dimer is a safe tool to exclude pulmonary embolism (PE) but its specificity is decreased in COVID-19. Aims: Our aim was to derive a new algorithm with D-dimer threshold adjusted to CT extent of lung damage. Methods: We conducted a multicenter, retrospective cohort study among 774 COVID-19 patients with suspected PE. D-dimer threshold adjusted to CT extent of lung damage was derived in a patient set ( n = 337), and its safety assessed in an independent validation set ( n = 337). Results: According to ROC curves, D-dimer safely excluded PE, with one false negative when using a 900 ng/mL threshold when lung damage extent was <50% and 1700 ng/mL when lung damage extent was ≥50%. In the derivation set, the algorithm's sensitivity was 98.2% (95% CI 94.7-100.0), and its specificity 28.4% (95% CI 24.1-32.3). The negative likelihood ratio (NLR) was 0.06 (95% CI 0.01-0.44) and the AUC was 0.63 (95% CI 0.60-0.67). In the validation set, sensitivity and specificity were 96.7% (95% CI 88.7-99.6) and 39.2% (95% CI 32.2-46.1), respectively. The NLR was 0.08 (95% CI 0.02-0.33), and the AUC did not differ from that of the derivation set (0.68 (95% CI 0.64-0.72), P = 0.097). Using the Co-LEAD algorithm, 76/250 (30.4%) COVID-19 patients with suspected PE could have been managed without CT pulmonary angiography (CTPA). Conclusions: The Co-LEAD algorithm safely excludes PE, and allows reducing the use of CTPA in COVID-19 patients. Prospective management studies are necessary to validate this strategy.