COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), profoundly affects the body’s vascular system in addition to causing respiratory illness. A pulmonary embolism (PE) is a serious condition where a major artery in the lungs becomes blocked, typically by a blood clot traveling from the deep veins of the legs. Infection with COVID-19 significantly increases the risk for developing PE, a complication resulting from the virus’s widespread impact on blood clotting mechanisms. This increased risk leads to a higher incidence of venous thromboembolism (VTE), which includes PE and deep vein thrombosis (DVT), especially in patients with severe illness.
How COVID-19 Triggers Clot Formation
The heightened risk of clot formation in COVID-19 patients stems from a complex interplay of three major biological pathways, creating a state known as hypercoagulability. The primary mechanism involves direct injury to the endothelial cells, which form the smooth inner lining of all blood vessels. SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) receptor to enter host cells, and these receptors are abundant on endothelial cells. Direct viral binding and subsequent invasion cause inflammation and death of these cells, a process termed endotheliitis.
Damage to the endothelium exposes pro-thrombotic molecules, initiating the coagulation cascade and disrupting the natural non-stick surface of the vessel walls. This endothelial dysfunction triggers the formation of microscopic clots (microthrombi) within the small vessels of the lungs. These microthrombi contribute to the severity of respiratory distress observed in many patients. The severity of the illness is often indicated by dramatically elevated levels of D-dimer, a protein fragment released when a blood clot breaks down.
Another powerful trigger for clotting is the systemic inflammatory response, often referred to as a “cytokine storm” in severe cases. The immune system overreacts to the virus, releasing excessive amounts of inflammatory molecules like Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-\(\alpha\)). This intense inflammation activates the coagulation system throughout the body, shifting the balance toward a pro-thrombotic state.
The inflammatory signals also directly affect blood components, causing overactivation of platelets, the cell fragments responsible for forming clots. Activated platelets become excessively sticky and aggregate more readily, contributing to the formation of larger macrovascular clots, such as those that cause PE. This combined effect of endothelial injury, inflammation, and platelet hyperactivation is responsible for the high incidence of thrombotic events seen during and after COVID-19 infection.
Recognizing the Signs of a Pulmonary Embolism
Recognizing the signs of a pulmonary embolism is important because the symptoms often overlap with the underlying COVID-19 illness. The most common warning sign of a PE is the sudden onset or worsening of shortness of breath (dyspnea), which can occur even while the patient is at rest. Since this symptom is difficult to differentiate from the respiratory distress caused by COVID-19 pneumonia, clinical suspicion is important.
Many patients also experience sharp or stabbing chest pain that typically worsens with deep breathing or coughing. This type of pain, known as pleuritic chest pain, arises when the clot irritates the lining of the lungs. Other signs that should prompt immediate medical attention include a rapid heart rate (tachycardia) and unexplained lightheadedness or fainting.
A less common but concerning symptom is coughing up blood or blood-streaked mucus (hemoptysis). Because PE symptoms can be non-specific or mimic an active COVID-19 infection, clinicians must maintain a low threshold for diagnostic testing, such as a CT pulmonary angiogram. The presence of a PE significantly increases in-hospital mortality and leads to a longer length of stay for COVID-19 patients.
Identifying High-Risk Patients
While COVID-19 is an independent risk factor for PE, certain patient characteristics significantly increase the vulnerability to this complication. The severity of the COVID-19 illness is a major predictor. Patients admitted to the hospital, particularly those requiring intensive care unit (ICU) admission or mechanical ventilation, have the highest risk. This is due to the combination of severe systemic inflammation and prolonged immobility, which is highly conducive to clot formation.
Pre-existing medical conditions also play a substantial role in identifying high-risk individuals.
Risk Factors
- Advanced age
- Obesity (Body Mass Index of 30 or greater)
- Prior history of a clotting event
- Comorbidities such as diabetes and pre-existing cardiovascular disease
The risk of venous thromboembolism is highest in the first 30 days following a COVID-19 diagnosis, even for individuals managed in an outpatient setting.
Current Treatment and Prevention Strategies
Given the high incidence of thromboembolic events, prevention (prophylaxis) with blood thinners is standard practice for nearly all hospitalized COVID-19 patients. Most guidelines recommend initiating prophylactic doses of anticoagulants, typically low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH), upon hospital admission. This intervention prevents clots from forming, even in patients without a confirmed PE.
For patients with a confirmed pulmonary embolism, the approach shifts to therapeutic anticoagulation, which involves administering higher, full-treatment doses of blood thinners. This therapeutic dosing aims to stop the existing clot from growing and allows the body to naturally dissolve it over time. In rare and severe cases of massive PE where the patient is hemodynamically unstable (hypotensive), more aggressive interventions may be necessary.
These severe cases may require thrombolytics, often called “clot-busting” drugs, administered to rapidly dissolve the blockage. Another option for unstable patients is catheter-directed therapy, where a specialist uses a thin tube to physically remove or break up the clot within the pulmonary artery. For high-risk patients discharged from the hospital, a limited period of extended prophylaxis with oral anticoagulants may be considered to prevent late-onset events.