Observed Higher Incidence of Pulmonary Embolism in COVID-19 Patients
A pulmonary embolism (PE) occurs when a blood clot that forms in a blood vessel in one area of the body (an embolus) breaks off and travels to a lung artery where it suddenly blocks blood flow. This can block the blood supply to a particular organ. This blockage of a blood vessel by an embolus is called an embolism. The most common symptoms for PE include sudden shortness of breath (most common), chest pain, dizziness, irregular heartbeat, palpitations, coughing and/or coughing up blood, and low blood pressure (1). PE is often difficult to diagnose because its symptoms are often found in many other conditions and diseases. However, along with a complete medical history and physical exam, tests used to look for a PE include chest X-ray, computed tomography (CT or CAT scan), and magnetic resonance imaging (MRI) (1). Interestingly, there appears to be a higher observed higher incidence of PE in COVID-19 patients. In March 2020, a study published in the European Heart Journal suggests a causal relationship between COVID-19 pneumonia and acute PE (APE) (2). Furthermore, according to a study submitted to the Lancet by Chen et. al, elevated level of D-dimer (a potential sign of PE) was reported in some patients with COVID-19 pneumonia on admission, especially in critically ill COVID-19 patients. However, it was still unknown whether this abnormality was associated with PE, as PE cannot be solely diagnosed by elevated D-dimer levels, because D-dimer can also be elevated in a series of other conditions such as cancer, peripheral vascular disease, pregnancy, and inflammatory diseases (3). Thus, the authors of the study aimed to confirm these findings through computed tomography pulmonary angiography (CTPA) in COVID-19 patients.
In this study, Chen et. al retrospectively identified 25 COVID-19 patients in total, who had CTPA examinations during the COVID-19 course, by searching in the electronic medical records database in the Central Hospital of Wuhan between January 2020 and February 2020. The Central Hospital of Wuhan hospitalized a total of 1008 patients with COVID-19 pneumonia between January 2020 and February 2020 (3). Diagnosis of COVID-19 pneumonia was based on Guidelines for the Diagnosis and Treatment of Novel Coronavirus (2019-nCoV) Infection published by the National Health Commission of China (Trial Version 5). All patients enrolled in the study were COVID-19 positive according to this clinical diagnostic criterion. They had undergone CTPA scans due to suspected PE and other clinical concerns and underwent D-dimer tests. Twenty patients received one or more follow-ups of the D-dimer test, and 3 patients underwent a follow-up CTPA examination to assess remission of PE after anticoagulant therapy. The interval between the CTPA examination and D-dimer test was less than 2 days. This study was approved by the Ethics of Committees of The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology. The need for patient informed consent was waived because of its retrospective nature (3).
A total of 25 patients (15 males and 10 females) were retrieved from the medical records. The median age was 65 years old (interquartile range (IQR): 56-70, range: 36-78 years). 15 of these patients were diagnosed positive for COVID-19 infection using RT-PCR, but the other 10
patients who tested negative using the RT-PCR test were diagnosed COVID-19 positive according to clinical diagnostic criteria. According to diagnostic criteria of COVID-19 classification, 11 cases (44%) were moderate and 14 cases (56%) were severe. Several chronic medical diseases, including hypertension (ten [40%]), diabetes (five [20%]), and cardiovascular disease (four [16%]) were recorded in some patients. By Feb 29, 2020, nine patients remained in hospital under close observation with improvement in symptoms, 10 patients were discharged, and 6 patients (2 with APE and 4 without APE on CTPA) had died. Abnormalities in laboratory tests were shown at the time when CTPA were performed. 10 patients were APE positive according to CPTA images, and had D-dimer levels with a median value of 1107μg/ml [IQR, 712-2166]; 15 patients were APE negative, and had D-dimer levels with a median value of 244μg/ml [IQR, 168-834]. There was a significant difference in D-dimer levels between the two groups with P < 0.05 (3). No significant difference was found between APE positive and APE negative groups for any other recorded laboratory data. In addition, twenty patients were treated with anticoagulant therapy (low molecular weight heparin, 0.6mg/kg per 12hours) regardless of any APE findings from CTPA and underwent a follow-up D-dimer test afterwards. The D-dimer levels decreased in all patients. For the 3 patients who underwent a follow-up CTPA examination after anticoagulant therapy, all APE lesions were smaller compared with the first CTPA examination, and the corresponding D-dimer levels also decreased (3). Among 10 patients with APE, six patients had bilateral pulmonary artery branches with thrombosis, and four patients had unilateral pulmonary artery branches with thrombosis. The thrombus-prone sites were the right lower lobe (70%), left upper lobe (60%), bilateral upper lobe (40%) and right middle lobe (20%).
Essentially, Chen et. al confirmed that there is indeed a relationship between elevated D-dimer levels (found in COVID-19 patients) and APE (3). However, it is still unclear why there is a higher incidence of APE in COVID-19 patients. Autopsy results of SARS patients showed that vascular thromboses were common in lung specimens, suggesting there may be an increased underlying thrombophilia in the lungs of people infected by coronaviruses. On the other hand, another autopsy study of 8 SARS patients showed that PE was found in the pulmonary arteries in 4 patients, in which 3 patients had deep vein thrombosis (DVT), which suggests that pulmonary artery thrombus derives from the deep vein of lower limb. Due to the COVID-19 quarantine requirement, the reduced physical movements of patients likely result in higher risk of DVT in patients’ lower limbs, leading to an increased incidence of PE (3).
References
- Pulmonary Embolism. (n.d.). Retrieved April 27, 2020, from https://www.hopkinsmedicine.org/health/conditions-and-diseases/pulmonary-embolism
- Gian Battista Danzi, Marco Loffi, Gianluca Galeazzi, Elisa Gherbesi, Acute pulmonary embolism and COVID-19 pneumonia: a random association?, European Heart Journal, , ehaa254, https://doi.org/10.1093/eurheartj/ehaa254
- Chen J., Wang X., Zhang S. Findings of acute pulmonary embolism in COVID-19 patients. The Lancet Infectious Diseases. 3/1/2020