key: cord-271840-cw2xy1m6 authors: Majmundar, Neil; Ducruet, Andrew; Prakash, Tannavi; Nanda, Anil; Khandelwal, Priyank title: Incidence, Pathophysiology, and Impact of Coronavirus Disease 2019 (COVID-19) on Acute Ischemic Stroke date: 2020-09-23 journal: World Neurosurg DOI: 10.1016/j.wneu.2020.07.158 sha: doc_id: 271840 cord_uid: cw2xy1m6 nan Although neurologic symptoms are rarely the initial chief complaints of patients affected by COVID-19, recent reports have implied that a significant percentage of patients may experience neurologic symptoms and a small percentage may even present with AIS as the presenting feature. 3, 4 Despite the known increased risk of stroke in patients with severe infections, many recent reports suggest an increased risk of AIS in patients with COVID-19, even in those with few risk factors for stroke. 2 AIS appears to occur in patients with COVID-19 with little regard to cardiovascular disease risk factors or age. Oxley et al. 4 reported 5 patients positive for COVID-19 in a New York City hospital system who presented with strokes secondary to largevessel occlusions (LVOs) over a 2-week period despite very few or no risk factors for stroke. A recent series from Wuhan suggested that the rate of AIS was 5% in patients with severe COVID-19 infection. 3 A recently published international collaboration has shown the incidence of stroke to be 1.3% (range 0.6%e2.6%) among 10 COVID hotspot centers. 5 Among 86 patients with AIS admitted in 10 hospitals, the majority of strokes were LVOs (60%) and median age of the LVOs patients was 51 years old, a significantly younger age group when compared with historical data. Several other reports implying causality between COVID-19 and stroke have also been published. 5 There have been several mechanisms proposed to explain this increased risk of thrombotic complications, especially strokes, in patients with COVID-19. SARS-CoV-2 uses the angiotensinconverting enzyme II (ACE2) receptor to gain entry into human cells. 2 The ACE2 receptor is heavily expressed in the nasal mucosa, lungs, small intestine, myocardium, vascular smooth muscle cells, and arterial and venous endothelial cells. 1 Inflammation and damage secondary to infection of these tissues, particularly the myocardium, may result in arrhythmias and increased risk of thrombus formation leading to stroke. 2 Furthermore, COVID-19 may result in a hypercoagulable state, possibly due to endothelial dysfunction, microthrombi formation, and the cytokine surge. 2 As an ACE2-seeking virus, capillary endothelial damage likely predisposes to a thromboembolic state. A synergistic contribution to endothelial damage mediated by antiphospholipid antibodies is also emerging as a possible cause. 2 There have also been several reports regarding elevated D-dimer levels in patients with COVID-19, reflecting a prothrombotic state as well as a poor prognosis ( Figure 1 ). 6 The association of COVID-19 and ischemic stroke is not yet fully understood. However, we are beginning to appreciate an association between the "thromboinflammation" caused by the virus and the increased risk of thrombotic/ischemic complications which can lead to strokes. 2,6 Due to the high rates of nosocomial transmission as well as the potential for overwhelming hospital resources, stroke centers across the world implemented new protocols for the triaging of patients with stroke, particularly those with LVOs requiring MT. 7 COVID-19 does not preclude patients who meet the criteria and guidelines set forth in the most recent randomized clinical trials from undergoing MT. This is a potentially lifesaving intervention that should not be withheld in eligible patients. Many centers have implemented stringent protocols, especially for the intubation of patients unlikely to tolerate MT with conscious sedation (e.g., high National Institutes of Health Stroke Scale, low Glasgow Coma Scale) to reduce the potential for aerosolization of respiratory particles in COVID-positive or potential-positive patients. 7 Ultimately, the practice changes implemented (e.g., conscious sedation vs. intubation, personal protective equipment precautions and door-to-puncture times, nosocomial rates of infection) will have to be investigated further to truly understand the impact of COVID-19 upon the delivery and practice of MT for LVOs ( Table 1) . While younger patients may be presenting with LVOs, many stroke centers across the world have anecdotally reported a decline in the total number of patients presenting with an ischemic stroke during the height of the pandemic. 8 Despite the link between COVID and a hypercoagulable prothrombotic state, there appears to have been a decline in patients presenting to hospitals with stroke symptoms. This is reflected by a recent publication demonstrating a 39% decrease in the use of stroke imaging during the early pandemic period (March 26 to April 8, 2020) when compared with the previous 29 days (February 1e29, 2020). 9 The early pandemic time period coincided with the implementation of "stay at home" recommendations across most of the United States. The decrease in stroke imaging volume could reflect the apprehensiveness of patients, especially those with mild symptoms wanting to avoid visiting healthcare facilities during the height of the epidemic. In addition, patients are taking longer to present to the hospital, potentially critically impacting the time window to intervene. Schirmer et al. and the Endovascular Neurosurgery Research Group published data demonstrating that patients had a significantly longer last known well to time of presentation interval during the COVID-era. 10 This finding has been corroborated by several institutions and groups across the world. 8 A recent study from a single center in New Jersey, one of the most heavily COVID-impacted states in the country, corroborated the decrease in overall stroke volume but also found a greater proportion of patients with stroke presenting with LVOs during the COVID-19 period. 8 This may suggest that while patients with milder symptoms may not be pursuing clinical care, patients who suffer from more debilitating symptoms secondary to LVOs are still seeking medical attention. Again, the impact of the pandemic upon patients with ischemic strokes will take some time to be understood. It will be interesting to study the trends once restrictions are lightened. Although the overall incidence of AIS in COVID-19 is not clear, there is emerging evidence that the rate of LVOs is increased in patients with COVID-19 who may not have the typical stroke risk factors. 4, 5 Developing protocols for timely diagnosis and providing hyperacute treatment in a time sensitive manner is the key to minimize mortality and morbidity in patients with AIS. We need further studies in an emergent fashion to fully understand the neuropathologic mechanism of AIS in patients with COVID-19. In addition, we will need to study long-term trends and outcomes to fully understand the impact of this pandemic upon patients with ischemic strokes. Cardiovascular considerations for patients, health care workers, and health systems during the COVID-19 pandemic Severe acute respiratory syndrome coronavirus 2 infection and ischemic stroke Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China Large-vessel stroke as a presenting feature of covid-19 in the young Incidence, characteristics and outcomes of large vessel stroke in COVID-19 cohort: a multicentric international study Hypercoagulation and antithrombotic treatment in coronavirus 2019: a new challenge Society of NeuroInterventional Surgery recommendations for the care of emergent neurointerventional patients in the setting of COVID-19 Falling stroke rates during COVID-19 pandemic at a Comprehensive Stroke Center: cover title: falling stroke rates during COVID-19 Collateral effect of covid-19 on stroke evaluation in the United States Delayed presentation of acute ischemic strokes during the COVID-19 crisis From the Departments of 1 Neurological Surgery and 2 1878-8750/$ -see front matter ยช 2020 Published by