Four coronavirus patients with pulmonary embolism were reported in this study. Patients were all from older age range. Indeed, older age has previously been associated with more severe forms of COVID-19 . Patients with COVID-19 often have respiratory symptoms, which make it hard to distinguish from pulmonary embolism in severe cases. Studies have shown that coronaviruses increase the risk of arterial and venous thromboembolism by causing inflammatory reactions, immobility, hypoxia, and disseminated intravascular coagulation (DIC) in patients . The co-occurrence and clinical symptomatic overlaps between pulmonary embolism and COVID-19 has made the diagnosis and treatment of PE more difficult. The presence of COVID-19 pneumonia can be easily detected with RT-PCR and CT scan [17, 18]. However, it is much more difficult to confirm PE; the reason for this is that factors influencing pro-inflammatory and hypercoagulability processes such as lactate dehydrogenase, ferritin, C-reactive protein, and interleukin levels are also increased in patients with coronavirus [19, 20]. In addition, recent studies have shown that levels of D-dimer, fibrinogen, and fibrin degradation products increase in patients with COVID-19 . It has also been shown that even in the absence of pulmonary embolism in patients with COVID-19, the level of D-dimer increases . An increase in D-dimer (> 1 mg/dL) is not a reliable indicator of venous thromboembolism [6, 22], although it may result in mortality. As a result, CT angiography can be helpful in diagnosing VTE in patients with coronavirus .
Developing PE have been associated with several risk factors including hypertension, coronary heart disease, malignancy, etc. . Examining medical history of the patients in this study did not show any specific risk factors leading to PE (Table 1). However, it is noteworthy that all four cases in this report were individuals in an older age range (Table 1), which not only increases the risk of developing PE , but also leads to more severe forms of COVID-19 . In general, investigating underlying diseases in detail can be useful in better understanding the causal factors of developing PE in patients with COVID-19.
The coagulation mechanism in COVID-19 is unknown. Some theories introduce cytokines as possible factors in the coagulation process in this disease, while others believe that hepatic dysfunction may be involved . Regardless of the coagulation mechanism in patients with coronavirus, it is known that the incidence of thrombosis increases in these patients. This coagulation often extends to intravascular coagulation and this expansion results in venous and arterial thrombosis. In addition, it has been shown that 71.4% of patients who died of COVID-19 met the criteria for diffuse intravascular coagulation . Many patients with COVID-19 face sepsis and septic shock . In the septic process, DIC is a major cause of organ dysfunction, so undergoing anticoagulant therapy in this situation can be very challenging .
Although, currently, there are no specific criteria for the use of anticoagulants in COVID-19 patients, heparin or/and other anticoagulants were prescribed for all the reported cases in this study according to an approval from the ministry of health in Iran. However, more clinical trials are needed to determine whether all patients with coronavirus need to be treated with anticoagulants. In general at this point, using PE prophylaxis based on clinical manifestations and D-dimer level, even in mild cases of COVID-19 seems to be important and necessary .
Due to insufficient information and different complications in patients with COVID-19, using or not using anticoagulants to improve the overall symptoms of the disease is still highly controversial . Two recent published studies by Klok et al. and Middeldorp et al. advised against prophylactically initiating treatment-dose anticoagulation in all patients with COVID-19 and in opposite, recommended using a lower threshold for proper diagnostic tests in assessing thrombotic complications including deep vein thrombosis and PE [30, 31].
Overall, two aims are recommended to be considered in the treatment of patients with COVID-19. The first goal is to protect the organs and timely diagnosis of events caused by the disease, which can be done by examining blood clot through D-dimer test or ultrasound. The second goal is to strengthen the immune system to prevent the formation of cytokine storms and blood clotting. For this purpose, norobion, zinc and vitamins are widely prescribed for patients with coronavirus in Iran, which were also used for all cases in this study. Further research into clinical trials is needed to clarify whether prophylactic treatment with anticoagulants leads to clinically beneficial outcomes in patients with COVID-19 infection.