Pulmonary Vasculature: A Target for COVID-19

To the Editor:

Coronavirus disease (COVID-19) is rapidly emerging and becoming a pandemic worldwide. The pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), infects the hosts via an ACE2 receptor, which is expressed in vascular endothelial cells. And SARS-CoV-2 has been found in blood vessels and causes a variety of vascular complications, including thrombosis (1). In a recent issue of the Journal, Patel and colleagues found a high rate of pulmonary embolism and distal pulmonary vascular dilation using computed tomography (CT) pulmonary angiography (CTPA) scans, and lung perfusion defects via dual-energy CT scans in patients with COVID-19 who were mechanically ventilated (2). It is the first report of peripheral pulmonary vessel dilation presenting as a vascular tree-in-bud pattern that was not reported in acute or chronic pulmonary embolism before. Interestingly, presence of peripheral pulmonary vessel dilation is associated with longer duration of hospitalization and ventilation. As SARS-CoV-2 infects blood vessels (1), the peripheral pulmonary vessel dilation could be caused by the virus infection or COVID-19–induced inflammation, which may be characteristic vascular damage in COVID-19 and associated with the severity of the disease. Lung pathology from patients with COVID-19 shows thrombus in the microvasculature (3), but whether these changes contribute to peripheral pulmonary vessel dilation in CTPA may need further investigation. In addition to lung CT examinations, thromboelastography was also performed on the patients in this study and showed hypercoagulability characterized by higher maximal amplitude and absent fibrinolysis at 30 minutes (lysis index 30 [LY30] = 0%). These thromboelastography findings may explain the reason why 38.5% of the patients had pulmonary embolisms even with anticoagulant prophylaxis, as the hypercoagulability state was mainly attributed to platelets and fibrin. Similarly, a recent study suggests that heparin treatment does not change mortality in severe COVID-19 cases (4). In contrast, a case series study suggests that tissue plasminogen activator treatment improved COVID-19–associated acute respiratory distress syndrome (5). Based on these findings, antiplatelet or fibrinolytic drugs could be studied for thrombosis prevention and treatment for patients with COVID-19 in the future.

However, this study raised several concerns. First, this study only included patients who underwent CTPA. The contrast medium used in CTPA may cause renal damage, which is also a common complication of COVID-19, and thus CTPA may not be routinely performed in patients with severe COVID-19 but only in those with suspected pulmonary embolism in the clinical practice. This may lead to a selection bias of patients and overestimate the rate of pulmonary embolism in patients with COVID-19 on mechanical ventilation, especially in such a retrospective study. Second, the average platelet counts were (272 ± 77) × 10⁹/L in the patients who received mechanical ventilation in this study, which were different from the previous cohort study in which thrombocytopenia has been reported to be common in patients who were critically ill with COVID-19 (6). Third, the therapy from pulmonary embolism was not discussed in this study; it would be interesting to discuss whether the treatment for pulmonary embolism in patients with COVID-19 should be different from pulmonary embolism treatment in patients without COVID-19.

Overall, Patel and colleagues’ study (2) is interesting in demonstrating a high rate of peripheral pulmonary vessel dilation and pulmonary embolism in patients with COVID-19, which may suggest that pulmonary vasculature is a common target of COVID-19. How these vascular changes affect COVID-19 development may need further study.