Adjusting D-dimer to Lung Disease Extent to Exclude Pulmonary Embolism in COVID-19 Patients (Co-LEAD).

Objective:  D-dimer measurement is a safe tool to exclude pulmonary embolism (PE), but its specificity decreases in coronavirus disease 2019 (COVID-19) patients. Our aim was to derive a new algorithm with a specific D-dimer threshold for COVID-19 patients.
Methods:  We conducted a French multicenter, retrospective cohort study among 774 COVID-19 patients with suspected PE. D-dimer threshold adjusted to extent of lung damage found on computed tomography (CT) was derived in a patient set ( n  = 337), and its safety assessed in an independent validation set ( n  = 337).
Results:  According to receiver operating characteristic curves, in the derivation set, D-dimer safely excluded PE, with one false negative, when using a 900 ng/mL threshold when lung damage extent was <50% and 1,700 ng/mL when lung damage extent was ≥50%. In the derivation set, the algorithm sensitivity was 98.2% (95% confidence interval [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 area under the curve (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 among 250 (30.4%) COVID-19 patients with suspected PE could have been managed without CT pulmonary angiography (CTPA) and 88 patients would have required two CTs.
Conclusion:  The Co-LEAD algorithm could safely exclude PE, and could reduce the use of CTPA in COVID-19 patients. Further prospective studies need to validate this strategy.
Competing Interests: T.M. reports personal fees and nonfinancial support from Bayer Healthcare SAS, personal fees and nonfinancial support from Incyte Biosciences, France, nonfinancial support from Alexion Pharma, France, nonfinancial support from Abbott, France, nonfinancial support from Amgen SAS, nonfinancial support from Boehringer Ingelheim, France, nonfinancial support from Bristol-Myers Squibb, no-financial support from MSD France, outside the submitted work; F.C. reports grants from Pfizer, personal fees from Bayer, other from Boehringer; grants, personal fees, and other from BMS; personal fees and other from Astra-Zeneca, other from GSK, personal fees from LEO-Pharma, other from Actelion, outside the submitted work; S.S. reports grants from LEO-Pharma, personal fees from Bayer, personal fees from BMS Pfizer, outside the submitted work; N.G. reports personal fees and nonfinancial support from Boehringer Ingelheim, personal fees and nonfinancial support from Bayer, personal fees from Bristol-Myers Squibb/Pfizer, personal fees from LEO-Pharma, personal fees from Aspen, outside the submitted work; O.S. reports grants, personal fees, and nonfinancial support from Bayer; grants, personal fees, and nonfinancial support from BMS; personal fees and nonfinancial support from Sanofi Aventis; personal fees and nonfinancial support from Boston Scientifics; personal fees from Pfizer; grants, personal fees, and nonfinancial support from MSD; grants and personal fees from Boehringer Ingelheim; grants from Daiichi Sankyo; personal fees from Chiesi; personal fees and nonfinancial support from BTG, outside the submitted work; L.K. reports personal fees from Bristol-Myers Squibb/Pfizer, outside the submitted work; M.A.S. reports personal fees and nonfinancial support from Bristol-Myers Squibb/Pfizer, personal fees and nonfinancial support from Bayer SA, grants, personal fees, and nonfinancial support from Leo-Pharma, personal fees from Aspen, outside the submitted work; R.C. reports personal fees from Aspen, outside the submitted work; D.M.S. reports grants from Boehringer Ingelheim, personal fees from Bayer, personal fees from Bristol-Myers Squibb/Pfizer, personal fees from Leo-Pharma, personal fees from Aspen, personal fees from Carmat, outside the submitted work; E.M. reports personal fees and nonfinancial support from Bayer, personal fees from Bristol-Myers Squibb/Pfizer, personal fees from Novartis, outside the submitted work; . N.M. reports grants and personal fees from Bayer Healthcare, grants and personal fees from BMS Pfizer, personal fees from Astra-Zeneca, personal fees from Terumo, grants and personal fees from Abbott, outside the submitted work; L.F. reports personal fees from Janssen, personal fees from Sanofi, personal fees from General Electrics, nonfinancial support from Guerbet, grants from Invectys, nonfinancial support from Philips, nonfinancial support from Ariana Pharma, nonfinancial support from Evolucare, outside the submitted work. All the other authors have nothing to declare.
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