Tomographic features of lung damage associate with D-Dimer levels and further clinical outcome in patients with acute respiratory distress syndrome due to COVID-19

Abstract

Background: Rapid progression of symptoms and development of Acute Respiratory Distress Syndrome (ARDS) frequently occurred during COVID-19 pandemic, while CT-Scan was useful to assess severity of lung damage, with classic patterns like early Ground Glass Opacity and/or late consolidation. Likewise, lung injury has been related to activation of the coagulation-fibrinolysis systems and pro-inflammatory mediators; where D-Dimer acquires prognostic relevance. The present study aimed to evaluate whether the extent of lung involvement and pattern of lung injury, as determined by chest CT-scan, are related with D-Dimer; and further impact clinical prognosis in patients with ARDS due to COVID-19.

Methods: Longitudinal, prospective, observational, multi-center study. Patients diagnosed with ARDS due to COVID-19, without previous lung damage, clotting disorder and/or anticoagulants use, who were attended at the Intensive Care Unit and Internal Medicine Department from March to June 2020. Tomographic extent of lung involvement was analyzed by image software, as well as damage patterns, assessed by experienced radiologists. Endpoints included relation of lung injury with coagulopathy markers like D-Dimer, and prognostic outcome including mortality, mechanical ventilation and hospitalization time.

Results: One-hundred and four patients mean aged 55 years old, 66% males, main comorbidities obesity, hypertension and diabetes mellitus. Larger lung damage was associated with older age, male gender and higher pro-inflammatory mediators like leukocytes and ferritin; whilst consolidation pattern was related to higher Body Mass Index. Higher values of D-Dimer were related either to a larger extent of lung involvement or late consolidation pattern. In addition, the extent of lung involvement was related with longer hospital stay, higher requirement of mechanical ventilation (HR 0.12, p < 0.01) and mortality rate (HR 0.13, p < 0.01); whereas late consolidation was mainly associated with requirement of mechanical ventilation (HR 0.23, p < 0.01).

Conclusion: Tomographic extent of lung involvement and the pattern of lung injury are related with coagulopathy severity markers like D-Dimer, and own prognostic clinical ability in ARDS.

Keywords: Acute respiratory syndrome; COVID-19; CT-scan; Consolidation; D-Dimer; Ground glass opacity; Lung injury.

Fig. 1

D-dimer and extent of lung involvement and pattern of lung injury (CT scan). Left. D-dimer values according to the percentiles of the extent of lung involvement, estimated as % of lung injury. Right. D-dimer values corresponding to consolidation or ground glass opacity patterns. Cutoffs: P25 = 24.5%, P50 = 38.6, P75 = 54.0. (*) = p < 0.05, one-way, T-test

Fig. 2

D-dimer and risk of lung injury. A. Risk association between D-dimer and the extent of lung involvement / pattern of lung injury (CT-Scan). Model 1 (unadjusted), Model 2 (adjusted by sex and age), Model 3 (adjusted by comorbidities), Model 4 (adjusted by inflammatory mediators). (*) Inflammatory mediators included C-reactive protein and ferritin. B: Forrest Plot of risk association between D-dimer and the extent of lung involvement / pattern of lung injury

Fig. 3

Lung injury and clinical outcome. Survival curves show the effect of A. the extent of lung involvement and B. the pattern of lung injury on severity outcomes (requirement of mechanical ventilation and mortality)