Pulmonary Embolism in COVID-19 Patients: Facts and Figures

*Nissar Shaikh, Narges Quyyum, Arshad Chanda, Muhammad Zubair, Muhsen Shaheen, Shajahan Idayatulla, Sumayya Aboobacker, Jazib Hassan, Shoaib Nawaz, Ashish Kumar, M.M. Nainthramveetil, Zubair Shahid and Ibrahim Rasheed*

### **Abstract**

COVID-19 infection affects many systems in the body including the coagulation mechanisms. Imbalance between pro-coagulant and anticoagulant activities causes a roughly nine times higher risk for pulmonary embolism (PE) in COVID-19 patients. The reported incidence of PE in COVID-19 patients ranges from 3 to 26%. There is an increased risk of PE in hospitalized patients with lower mobility and patients requiring intensive care therapy. Obesity, atrial fibrillation, raised pro-inflammatory markers, and convalescent plasma therapy increases the risk of PE in COVID-19 patients. Endothelial injury in COVID-19 patients causes loss of vasodilatory, anti-adhesion and fibrinolytic properties. Viral penetration and load leads to the release of cytokines and von Willebrand factor, which induces thrombosis in small and medium vessels. D-dimers elevation gives strong suspicion of PE in COVID-19 patients, and normal D-dimer levels effectively rule it out. Point of care echocardiogram may show right heart dilatation, thrombus in heart or pulmonary arteries. DVT increases the risk of developing PE. The gold standard test for the diagnosis of PE is CTPA (computerized tomographic pulmonary angiography) which also gives alternative diagnosis in the absence of PE. Therapeutic anticoagulation is the corner stone in the management of PE and commonly used anticoagulants are LMWH (low molecular weight heparin) and UFH (unfractionated heparin). Mortality in COVID-19 patients with PE is up to 43% compared to COVID patients without PE being around 3%.

**Keywords:** COVID-19, computerized tomographic pulmonary angiography, D-dimer, pulmonary embolism, unfractionated heparin, ultrasonography

### **1. Introduction**

COVID-19 infection is primarily a respiratory viral infection, initially described in China and despite restrictive and preventive measures, it spread quickly and within few months became a global pandemic. Although COVID-19 is a respiratory infection, it can cause multiple organ dysfunctions and is thus a constant threat to the life. Hypercoagulable state is a well-known complication particularly in severely ill COVID-19 patients. This increases the risk of thromboembolism, particularly pulmonary embolism (PE) [1]. The presence of pulmonary embolism in COVID-19 patients creates a challenging clinical scenario due to their already compromised respiratory function. Early recognition and therapeutic intervention are critical for better patient management and a positive outcome.

We will discuss the occurrence of PE in COVID-19 infection in following sub-headings.

### **2. Epidemiology**

The incidence of PE in COVID-19 patients is underdiagnosed and varies depending on patient's condition and level of care being provided, but there is an overall 9 folds increased risk of PE in COVID-19 patients compared to the non-COVID population [1]. Overall incidence as well as mortality of PE due to traditional risk factors is decreasing but there are increased incidence and mortality of PE in COVID-19 patients [1]. PE incidence increases further in COVID-19 patients requiring intensive care unit (ICU) admission and one out of three patients in the ICU may have PE. Ng et al. reported the incidence of PE in ICU varies from 3.3 to 26.7% [2]. The evidence of under diagnosis of PE in COVID-19 patients is provided by the fact that a chest CT scan performed in COVID-19 patients regardless of clinical manifestations, showed PE in 50% of the patients [3]. Incidence of PE in COVID-19 patients irrespective of their admission to the hospital or not is reported to be 1.1 to 3.4% [4].

The incidence of PE in the hospitalized patients is reported to be ranging from 1.9 to 8.9% in different studies, being particularly high in critically ill patients (up to 26.6%) [5]. Liu et al. reported that one in five patients with a mean age of 57 years and having comorbid conditions developed PE [6].

### **3. Risk factors**

The risk factors of thromboembolism or PE in COVID-19 patients are not the same as traditional PE risk factors. Traditional risk factors including lower limb fractures, heart failure, hip or knee replacement surgeries, myocardial infarction, spinal trauma, post-partum period do not seem to increase the risk in COVID-19 patients, but sure there will be some relevance of these conditions on the occurrence of PE [7]. African American race and obesity are found to increase the risk of PE in COVID-19 patients. There is no strong relationship between cardiovascular comorbidities and the risk of pulmonary embolism in COVID-19 patients [7]. Various studies reported that the clinical and biological parameters in COVID-19 patients driven by inflammation and coagulopathy increase the risk of PE. Presence of severe inflammation with increase in D-dimers, C-reactive protein (CRP), high fractional inspiration of oxygen and development of ARDS (acute respiratory distress syndrome) were associated with increased risk of PE. Demographic factors increasing risk of PE included male gender, history of stroke, atrial fibrillation, chest pain and dyspnea [7]. COVID-19 patients requiring ECMO (Extracorporeal membrane oxygenation) and convalescent plasma therapy were also at a higher risk of PE [7]. Up to 39% of COVID-19 patients requiring invasive ventilation develop PE [7].

Overall, from the literature it seems that mild to moderate COVID-19 infections, patients with delayed onset of symptoms and hospitalization have increased risk of PE [7, 8].
