Perspective: The Case for Acute Large Vessel Ischemic Stroke in COVID-19 Originating Within Thrombosed Pulmonary Venules

Abstract

The main burden of SARS-CoV-2 falls on the lungs but neurological manifestations, the most disabling of which are strokes and which correlate with disease severity, are common. We proffer a novel mechanism for acute COVID-19 stroke whereby pulmonary vein clots developing within the characteristic pulmonary intravascular thrombotic lesions can embolize to the brain. Appreciation of this mechanism requires an understanding of the tricompartmental model of lung parenchyma oxygenation (the alveolus, the bronchial artery, and the pulmonary artery), all of which are compromised in COVID-19. Of these 3 sources, the bronchial artery plays a crucial role in COVID-19 stroke because the unique collaterals from bronchial artery to pulmonary vein which exist under normal physiological conditions (and which maintain venous patency when the pulmonary artery is blocked by embolus) are occluded, thus leading to venular thrombosis in the presence of hypercoagulability. Dislodgement of clots from this source translocates the pathology to the brain and is a disease mechanism, formerly rare, which may account for many cases of large vessel occlusion stroke in COVID-19. This mechanism extends the concept of cardioembolic stroke from endocardium retrogradely into the pulmonary circulation with which the left cardiac chambers lie in direct continuity, and which is an accepted stroke mechanism under other circumstances such as lung lobectomy, where surgical ligation of the pulmonary vein creates a blind sac from which thrombi can embolize. The proposed model is supported by postmortem studies which have demonstrated venular thrombosis and by case reports of pulmonary vein thrombosis in COVID-19. This concept provides a more plausible cause for COVID-19 associated large vessel occlusion stroke than other putative mechanisms, such as cerebral endotheliitis, cytokine storm, and hypercoagulopathy, although it is acknowledged that the latter mechanism contributes to the genesis of pulmonary vein clots. Recognizing that extrapulmonary manifestations including stroke arise within thrombosed pulmonary veins is key to understanding of neurological manifestations of SARS-CoV-2 infection.

Patients with COVID-19 Infection and Stroke have Higher than Expected Mortality, Regardless of the Primary Presentation

“…[4][5][6][7] Several mechanisms have been proposed including endothelial injury, inflammation, complement activation, and deactivation of antithrombotic pathways. 8 An interesting model, based off postmortem studies and these mechanisms, postulates that injury to the lung tri-compartment (pulmonary artery, bronchial artery, and alveolus) leads to pulmonary vein thrombosis and subsequent large vessel occlusion (LVO) 9 . In terms of demographics, COVID-19 patients who suffered strokes are also demographically different from traditional stroke patients.…”

Effects of bundle‐care interventions on pressure ulcers in patients with stroke: A meta‐analysis

“…Stroke, which is common in middle‐aged and older adults, is an acute cerebrovascular disease caused by cerebral ischaemia due to cerebral blood vessel blockage or rupture, with high morbidity, disability and mortality rates 6,7 . The majority of patients with stroke experience hemiparesis or hemiplegia and other limb weakness 8,9 . During clinical treatment of patients with stroke, local tissues are compressed due to prolonged bed rest and are prone to nutritional deficiencies and ischaemia, especially in tissues with bone protrusions, which increases the risk of pressure ulcers 6 .…”

“… 6 , 7 The majority of patients with stroke experience hemiparesis or hemiplegia and other limb weakness. 8 , 9 During clinical treatment of patients with stroke, local tissues are compressed due to prolonged bed rest and are prone to nutritional deficiencies and ischaemia, especially in tissues with bone protrusions, which increases the risk of pressure ulcers. 6 It is difficult to cure pressure ulcers after stroke, and effective measures to prevent pressure ulcers from occurring are therefore important.…”