Ischemic stroke and intracerebral hemorrhage in patients with COVID-19

Introduction. Patients with coronavirus disease 2019 (COVID-19) can exhibit neurological symptoms and diseases. A few studies have focused on cerebrovascular diseases in patients with COVID-19. In the present study, we as-sessed medical records of patients with COVID-19 with stroke. Material and methods. Forty-seven COVID-19 patients with stroke were consecutively selected and reviewed. Medical records of the patients including information on age, gender, severity of pulmonary involvement (intubation or non-intubation) in COVID, presence of ICH and ischemic stroke, localization of ICH, history of diabetes and hyper- tension were collected. results. Twenty-three COVID-19 patients (49%) had ICH and 24 COVID-19 patients (51%) had ischemic stroke. Sixteen COVID-19 patients with ICH (69.6%) had lobar hemorrhage and 7 COVID-19 patients with ICH (30.4%) had non-lobar hemorrhage (p =0.093). conclusions. In this study, ICH and ischemic stroke were present at roughly the same rate in COVID-19 patients with stroke. Lobar hemorrhage was seen more frequently in COVID-19 patients with ICH. Brain and cerebrovascular imaging can be a helpful component of the work-up in COVID-19 patients.


MAtErIALs AND MEtHOD
the present retrospective study was carried out in Poursina Hospital of Rasht, Iran. Forty-seven COVID-19 patients with cerebrovascular disease were consecutively selected and reviewed. COVID-19 and cerebrovascular disease were confirmed by lung and head computed tomography (ct). Medical records of the patients including information on age, gender, severity of pulmonary involvement (intubation or non-intubation) in COVID, presence of ICH and ischemic stroke, localization of ICH, history of diabetes and hypertension were collected. age was also dichotomized in ICH patients as < 50 years and ≤ 50 years as ICH is more common in individuals with more than 55 years of age [13]. The study was analyzed by SPSS (version 24) using independent t-test and chi-square analysis. The study was approved by Guilan University of Medical sciences ethics committee. rEsULts in this study, 47 patients with cOViD-19 and stroke were reviewed. Twenty-three patients (49%) had ICH and 24 patients (51%) had ischemic stroke ( Figure 2). the mean±standard deviation (sD) of the age of COVID-19 patients with ICH was 69.43±9.83 years, and the mean±SD of the age of cOViD-19 patients with ischemic stroke was 73.13±11.76 years (P-value > 0.05).

DIscUssION
COVID-19 primarily affects the respiratory system, yet it has also shown multi-organ dysfunction. several lines of evidence have indicated neurotropism of SARS-CoV-2. The SARS-CoV-2 ribonucleic acid (RNA) has been detected in cerebrospinal fluid (CSF) [2]. A wide variety of neurological symptoms and disorders have been reported in patients with COVID- 19. It has been demonstrated that SARS-CoV-2 can influence the cerebrovascular system and give rise to stroke. stroke is a leading cause of death [14] and has serious worldwide health consequences [15], especially in the elderly [16]. Blood pressure (BP) control and anticoagulant administration are implemented to prevent stroke [17]. cOViD-19-associated coagulopathy (cac) is a severe coagulopathy due to inflammation, including inflammatory cytokine storm [18]. Systemic inflammation and inflammatory biomarkers, such as serum IL-6 [19], are associated with risk of ischemic stroke.
Immune thrombocytopenia purpura in a man with COVID-19 with subarachnoid hemorrhage in the right frontal lobe of the brain was reported [20]. an elderly patient with cOViD-19 was shown to have a massive ICH in the right hemisphere, in addition to intraventricular and subarachnoid hemorrhage [8]. Five COVID-19 patients (age <50 years) with large-vessel stroke were reported [21]. a case report showed a cOViD-19 patient with hyperdensity in the superior sagittal, right transverse, and sigmoid sinuses, as well as upper right internal jugular vein indicating thrombosis of cerebral venous sinus [22]. Due to large blood vessel occlusion and acute cerebral infarction, a COVID-19 patient exhibited left hemiparesis [7]. Several arterial thromboses of brain, hands, and legs were demonstrated to be associated with antiphospholipid antibodies in 3 patients with cOViD-19 [23].
Despite relative variability, ICH encompasses 10-20% of all strokes in most populations [25]. Interestingly, in our study, ICH was seen in 49% of stroke patients with cOViD-19, approximately as much as the rate of ischemic stroke (51%). To the best of our knowledge, this is the first study reporting an almost equal rate of ICH and ischemic stroke in patients with cOViD-19. the reason why the rate of ICH constitutes a considerable proportion of stroke patients with COVID- 19 has not yet been studied. However, a possible mechanism may be increased levels of oxidative stress and the inflammatory response in cOViD-19. Divani et al. argued that higher oxidative stress and the inflammatory response may be due to overactivation of the classical pathway of renin angiotensin system (ras) pathway along with underactivation of the alternative RAS pathway in COVID-19 [18]. SARS-COV-2 binds to the ACE2 receptor on the cellular membrane, which has an important role in RAS [18].
In terms of localization of ICH, non-lobar hemorrhage is more common than lobar hemorrhage in the general population [26]. interestingly, however, we found that lobar hemorrhage (69.6%) is more common than non-lobar hemorrhage (30.4%) in ICH patients with COVID-19. It is worth mentioning that downregulation of ace2, which is presumed to happen by SARS-COV-2, can trigger vasoconstriction through activation of the ras classical pathway.
In our study and concordant with the findings of giroud et. al in a general population, we found that most of the ICH patients with COVID-19 were over the age of 55 [13].
Large vessel blockage in ischemic stroke is mostly seen in the territory of the internal carotid artery and the MCA [27,28]. In the present study, most of the blockage occurred in the MCA territory in cOViD-19 patients with ischemic stroke.
We found that 8.7 % of COVID-19 patients with ICH had a medical history of diabetes DM2; whereas, 20.8% COVID-19 patients with ischemic stroke had a medical history of DM2. a medical history of hypertension was found in 34.8% of COVID-19 patients with ICH and 62.5% of cOViD-19 patients with ischemic stroke.

cONcLUsIONs
ICH and ischemic stroke were present at roughly the same rate in cOViD-19 patients with stroke. Lobar hemorrhage was seen more frequently in COVID-19 patients with ICH. Brain and cerebrovascular imaging can be a helpful component of the work-up in cOViD-19 patients.