Acute Pulmonary Embolism Associated with COVID-19 Pneumonia Detected with Pulmonary CT Angiography
Chest CT plays an important role in optimizing the treatment of patients with coronavirus disease 2019 (COVID-19) while also eliminating alternate diagnoses or added pathologic conditions, particularly for acute pulmonary embolism (1). A few studies and isolated clinical cases of COVID-19 pneumonia with coagulopathy and pulmonary embolus have recently been published (2–4). The main objective of our study was to evaluate pulmonary embolus in association with COVID-19 infection by using pulmonary CT angiography.
Materials and Methods
This retrospective study was approved by our institutional review board. It followed the ethical guidelines of the Declaration of Helsinki. The requirement for written informed consent was waived. Three authors (F.G., J.B., P.C.) had access to the study data. No author has any conflict of interest to declare in relation to this study.
The inclusion criteria were consecutive adult patients (≥18 years) with a reverse-transcription polymerase chain reaction diagnosis (NucleoSpin RNA virus kit; Macherey-Nagel, Bethlehem, Pa) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or a strong clinical suspicion of COVID-19 (fever and/or acute respiratory symptoms, exposure to an individual with confirmed SARS-CoV-2 infection) who underwent chest CT between March 15 and April 14, 2020, at a single center. In patients suspected of having or confirmed to have SARS-CoV-2 infection, chest CT was performed when clinical features of severe disease were present (eg, mechanical ventilation was required or the patient had underlying comorbidities). Patients with unenhanced chest CT scans were excluded.
Our routine protocol for patients with severe clinical features of COVID-19 infection was multidetector pulmonary CT angiography using a 256-slice multidetector CT scanner (Revolution; GE Healthcare, Milwaukee, Wis) after intravenous injection of 60 mL iodinated contrast material (Iomeprol, 400 mg of iodine per milliliter; Bracco Imaging, Milan, Italy) at a flow rate of 4 mL/sec, triggered on the main pulmonary artery. CT scan settings were as follows: 120 kVp, collimation of 80 × 0.625 mm, rotation time of 0.28 second, average tube current of 300 mA, pitch of 0.992, and volume CT dose index of 4.28 mGy.
The chest CT scan pattern of COVID-19 and presence of pulmonary embolus were independently analyzed by two chest radiologists (J.B. and F.G., with 11 and 6 years of experience, respectively) using a picture archiving and communications system workstation (Carestream Health, Rochester, NY). Readers were blinded to patient status as well as to clinical and biologic features. In cases of discordance, a simultaneous reading to reach consensus was achieved.
Comparisons between continuous variables were performed by using the Student t test when distribution was normal. Comparisons between categoric variables were performed by using the Pearson χ2 test or Fisher exact test. To determine the clinical factors associated with pulmonary embolus, we considered the CT extent of lesions, need for invasive mechanical ventilation, demographic characteristics, and presence of comorbidities as potential independent variables in a logistic regression model. P < .05 was indicative of a significant difference. All analyses were performed with R version 3.4.4 software (R Core Team 2017, R Foundation for Statistical Computing, Vienna, Austria).
Of 2003 patients diagnosed with COVID-19, 280 were hospitalized during the study period. Of these 280 patients, 129 (46%) underwent CT a mean of 9 days ± 5 (standard deviation) after symptom onset. Twenty-nine patients underwent unenhanced chest CT due to contraindication to iodinated contrast material or nonsevere clinical features; thus, these patients were excluded. Finally, 100 patients with COVID-19 infection and severe clinical features were included and examined with contrast material–enhanced CT (Fig 1). The mean age of the included patients was 66 years ± 13, and there were 70 men and 30 women (Table).
Of the 100 patients meeting the inclusion criteria, 23 (23%, [95% confidence interval: 15%, 33%]) had acute pulmonary embolism (Fig E2, Appendix E1 [online]). Patients with pulmonary embolus were more frequently in the critical care unit than those without pulmonary embolus (17 [74%] vs 22 [29%] patients, respectively; P < .001), required mechanical ventilation more often (15 of 23 patients [65%] vs 19 of 77 patients [25%], P < .001), and had longer delay from symptom onset to CT diagnosis of pulmonary embolus (mean, 12 days ± 6 vs 8 days ± 5, P < .001) (Table). At multivariable analysis, requirement for mechanical ventilation (odds ratio = 3.8 [95% confidence interval: 1.02, 15], P = .049) remained associated with acute pulmonary embolus (Table E3, Appendix E1 [online]).
Our study points to a high prevalence of acute pulmonary embolism in patients with coronavirus disease 2019 (23% [95% confidence interval: 15%, 33%]). Pulmonary embolus was diagnosed a mean of 12 days from symptom onset. Patients with pulmonary embolus were more likely to require care in the critical care unit and to require mechanical ventilation compared with those without pulmonary embolus.
Current guidelines (1,5,6) recommend performing unenhanced chest CT to assess the COVID-19 CT pattern and its extension. However, previous reports suggested coagulopathy associated with COVID-19 infection (2,3). Furthermore, these patients have frequent risk factors for pulmonary embolus (eg, mechanical ventilation, intensive care unit admission). Therefore, we routinely performed contrast-enhanced CT for patients with COVID-19 with severe clinical features to evaluate the lung parenchyma as well as to evaluate other complications that may result in respiratory distress.
Our results showed frequent (23%) pulmonary embolus in patients with COVID-19. At multivariable analysis, pulmonary embolus was associated with invasive mechanical ventilation and male sex. Interestingly, extent of lesions was not associated with pulmonary embolus. We acknowledge the preliminary nature of these findings, including its retrospective nature and limited sample size. Important clinical markers were not available that may explain or be associated with pulmonary embolus, including d-dimer level (only 22 of the 100 patients had d-dimer levels available). Nevertheless, our results suggest that patients with severe clinical features of COVID-19 may have associated acute pulmonary embolus. Therefore, the use of contrast-enhanced CT rather than routine unenhanced CT may be considered for these patients.
Author contributions: Guarantors of integrity of entire study, F.G., J.B., E.D.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; agrees to ensure any questions related to the work are appropriately resolved, all authors; literature research, F.G., J.B., E.D.; clinical studies, F.G., J.B.; statistical analysis, P.C.; and manuscript editing, all authors
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Article HistoryReceived: Apr 11 2020
Revision requested: Apr 18 2020
Revision received: Apr 19 2020
Accepted: Apr 20 2020
Published online: Apr 23 2020
Published in print: Sept 2020