Major neurological syndromes with COVID-19: lessons to learn

Objective: Covid-19 is a highly infectious viral disease, and our understanding of the impact of this virus on the nervous system is limited. Therefore, we aimed to do a systematic analysis of the neurological manifestations. Methods: We retrospectively studied the clinical, laboratory, and radiological findings of patients with major neurological syndromes (MNS) in Covid-19 over 6 months. Results: We had 39 patients with major neurological syndromes (MNS). The most common MNS was cerebrovascular disease (CVD) (61.53%), in which ischemic stroke (83.33%), cortical sinus thrombosis (12.50%), and haemorrhagic stroke (4.16%) were seen. Among ischemic stroke patients, 50% had a large vessel occlusion, and 66.66% of patients with CVD had a significant residual disability. Cranial neuropathy (15.38%), GBS (10.26%), encephalitis (7.26%), and myelitis (5.12%) were the other MNS. Among the three encephalitis cases, two had CSF-Covid-19 PCR positivity and had severe manifestations and a poor outcome. Associated comorbidities included hypertension (30.76%), diabetes mellitus (12.82%), chronic kidney diseases (7.69%), and polycythaemia vera (2.56%). Lung involvement was seen in 64.1% of patients. Mortality was 17.94% in MNS with Covid-19. Conclusions: The most common major neurological syndrome associated with Covid-19 is CVD with increased frequency of large vessel occlusion causing significant morbidity and mortality. Simultaneous lung and other systemic involvement in MNS results in a deleterious outcome.

Neurologic presentations of COVID-19: a case series

Introduction: The new pandemic of coronavirus disease 2019 (COVID-19) has evolved certain neurologic syndromes as a presentation of this disease that should be integrated into the whole disease process. Case Presentations: We present cases of neurologic involvement in adult patients with documented bronchopulmonary COVID-19. Certain signs and symptoms are introduced, including new onset seizures, ischemic stroke, and altered mental status in otherwise minimal clinical signs and symptoms of COVID-19. Conclusions: Many neurologic presentations are diagnosed in resolving COVID respiratory infections or in an otherwise asymptomatic individual.

Does COVID-19 increase risk of stroke?

Aim: In this study, it was aimed to compare the epidemiological characteristics and frequency of patients diagnosed with stroke in Kayseri City Hospital in the pre-COVID-19 pandemic period and during the COVID-19 pandemic and investigate whether COVID-19 increases the frequency of stroke. The true relationship between COVID-19 and the incidence of stroke has yet to be determined. Materials and Methods: A meta-analysis study reported that 1.4% (95%CI: 1.0-1.9) of 108,571 patients with COVID-19 developed acute cerebrovascular disease (CVD). Additionally, although the number of hospital admissions due to clinical presentation of suspected stroke decreased due to the pandemic, it has been suggested that the COVID-19 infection itself may cause a stroke. Results: In the literature, there have been reports of patient groups who developed ischemic stroke 1-2 weeks after diagnosis with typical COVID-19 symptoms, as well as patient groups who developed symptoms such as fever, dry cough, and shortness of breath during follow-up with ischemic stroke and who were subsequently diagnosed with COVID-19 . It was observed that patients presented with sudden onset loss of strength showing side without typical COVID-19 symptoms (such as cough, fever), and thoracic CT scans of these patients in the later period revealed pulmonary findings. Conclusion: In other words, COVID-19 patients may present with neurological symptoms such as acute cerebrovascular disease as the first symptom.

Evaluation of stroke frequency in COVID-19 patients

Objective: Neurological symptoms occur due to central and peripheral nervous system involvement with different mechanisms in coronavirus disease 2019 (COVID-19). Microvascular thrombosis develops with prothrombotic activation along with the increase in cytokines in COVID-19 infection. We aimed to investigate the incidence of cerebrovascular disease and concomitant risk factors in COVID-19 positive patients. Materials and Methods: Acute and temporally related cerebrovascular diseases with a diagnosis of COVID-19 were evaluated. Cerebrovascular events were assessed in 4 groups as ischemic and hemorrhagic events, transient ischemic attacks, and cerebral venous thrombosis. Risk factors for cerebrovascular disease in these patients were also assessed, and which risk factors for cerebrovascular diseases in COVID-19 patients are high risk were examined. Results: Of the 1000 patients with COVID-19 disease were evaluated. Ischemic cerebrovascular disease and/or transient ischemic attack were found in 14 patients (1.4%). The most common symptoms related to COVID-19 were fever and respiratory distress in 14 patients with acute ischemic stroke diagnosed with COVID-19. Conclusion: COVID-19 increases the risk of stroke in patients with multiple risk factors. Close follow-up should be performed more carefully, especially in patients with pulmonary involvement and acute ischemic stroke, because mortality is likely to be higher.

Neurological manifestations in patients with COVID-19

Introduction: COVID-19 pandemic represents a challenge for healthcare systems, due to the impact on different systems, such as respiratory, cardiovascular and nervous systems. Background: to describe the neurological manifestations in patients with COVID-19. Methods: a search for information was carried out in the PubMed/Medline, SciELO, EBSCO, Lilacs and Scopus databases. A search strategy was applied by combining terms and using Boolean operators. Thirty references were chosen. Results: olfactory nerves and invasion of peripheral nerve terminals are suggested as routes of entry;the presence of severe neural symptoms associated with lesions of other organs and cytokine storm is also described. Headache was the most common neurological manifestation in patients with COVID-19, and rhabdomyolysis, acute hemorrhagic necrotizing encephalopathy, Guillain Barre syndrome, meningitis and encephalitis are rare neurological entities. In Guillain Barre syndrome, the literature suggests both a post infectious and para-infectious pattern. Conclusions: COVID-19 is associated with different neurological manifestations, including headache, dizziness, vertigo, vomiting, and alterations of consciousness, stroke and others not so frequent. These symptoms as a whole should be evaluated by healthcare personnel, with a view to their rapid detection and management, in order to guarantee the disappearance of sequelae that reduce the quality of life of patients, as well as to reduce the associated mortality records.

Antiphospholipid syndrome, antiphospholipid antibodies, and stroke.

Antiphospholipid syndrome (APS) is a prothrombotic autoimmune disease with heterogeneous clinicopathological manifestations and is a well-established cause of acute ischemic stroke (AIS) and transient ischemic attack (TIA), particularly in younger patients. There is growing recognition of a wider spectrum of APS-associated cerebrovascular lesions, including white matter hyperintensities, cortical atrophy, and infarcts, which may have clinically important neurocognitive sequalae. Diagnosis of APS-associated AIS/TIA requires expert review of clinical and laboratory information. Management poses challenges, given the potential for substantial morbidity and recurrent thrombosis, additional risk conferred by conventional cardiovascular risk factors, and limited evidence base regarding optimal antithrombotic therapy for secondary prevention. In this review, we summarize key features of APS-associated cerebrovascular disorders, with focus on clinical and laboratory aspects of diagnostic evaluation. The current status of prognostic markers is considered. We review the evidence base for antithrombotic treatment in APS-associated stroke and discuss uncertainties, including the optimal intensity of anticoagulation and efficacy of direct oral anticoagulants. Clinical practice recommendations are provided, covering antithrombotic treatment, supportive management, and options for anticoagulant-refractory cases, and we highlight the benefits of adopting a considered, multidisciplinary team approach.

Superior Cerebellar Artery Dissection in a Patient Diagnosed with Reversible Cerebral Vasoconstriction Syndrome: A Case Report

Arterial dissection is an uncommon complication of reversible cerebral vasocon-striction syndrome (RCVS). We describe the case of a 35-year-old woman with a migraine history who presented with recurrent thunderclap headache and focal neurological signs, including right hemiataxia. She had been diagnosed with COVID-19 disease two weeks earlier. Neuroimaging revealed multifocal stenosis of the posterior circulation arteries and dissection of the right superior cerebellar artery. She improved significantly throughout her one-week hospitalization and maintained only mild ataxia. The interplay between COVID-19 disease, RCVS, and arterial dissection requires further investigation.Copyright © Author(s) (or their employer(s)) and Sinapse 2022.

Assessment of role of HRCT, RT-PCR in the evaluation of COVID-19 symptomatic patients

Background: To assess role of HRCT, RT-PCR in the evaluation of COVID-19 symptomatic patients. Material and Methods: This retrospective study was conducted in the department of Radiology and Microbiology at Aarupadaiveedu Meddical College and Hospital . Eighty- five clinically suspects of COVID-19 patients of either gender was enrolled in the study and underwent RT-PCR test and HRCT Thorax . HRCT images were studied by Three radiologists independently. CURB- 65 and SOFA was recorded. Results: There were 50 males and 35 females in our study. Disease severity CURB was 1 and SOFA was 3. Chest CT had suspicious for COVID-19 in 45 and RT-PCR SARS-CoV2 positive in 40.42 had no comorbidity, 8 had peripheral vascular disease, 12 had cerebrovascular disease 13 had hypertension and 10 had diabetes mellitus. The difference was significant (P< 0.05). In all 40 patients of PCR SARS-CoV-2 positive, 35 HRCT were judged as suspicious for COVID-19. In 45 cases of PCR SARS-CoV-2 negative, 10 HRCT scans were judged as not suspicious for COVID-19. HRCT Thorax had a sensitivity of 87.5%, specificity of 77.8%, PPV of 77% and NPV of 87.5%. Conclusion: The diagnostic accuracy of HRCT Thorax in symptomatic patients is good, but not good enough to safely diagnose or exclude COVID-19 patients. RT- PCR is useful in addition with HRCT in diagnosis of COVID-19 patients.

Emergency department visits by adults with chronic conditions associated with severe COVID-19 illness: United States, 2017-2019

Objective: This report describes emergency department (ED) visits made by adults with selected chronic conditions associated with severe COVID-19 illness. Methods-Estimates in this report are based on data collected in the 2017-2019 National Hospital Ambulatory Medical Care Survey. Sample data were weighted to produce annual national estimates. Patient characteristics, including age, sex, expected source of payment, medication prescriptions, and hospital admission status, are presented by number of chronic conditions. Selected chronic conditions associated with severe COVID-19 illness include Alzheimer disease or dementia, asthma, cancer, cerebrovascular disease, chronic kidney disease, chronic obstructive pulmonary disease, depression, diabetes, heart disease, HIV, hypertension, obesity, pulmonary embolism, and substance use disorders. Results-For 2017-2019, 59.5% of ED visits made by adults were among those with one or more chronic conditions. The percentage of ED visits made by adults with three or more chronic conditions was highest among those aged 45-64. Medicare was the most frequently observed expected source of payment among adults with three or more chronic conditions. The percentage of ED visits that resulted in a hospital admission increased with the number of chronic conditions. Overall, hypertension was the most frequently observed chronic condition (33.8% of ED visits by adults) and hypertension and diabetes was the most frequently observed dyad, or pair (33.2% of ED visits by adults with at least two chronic conditions). Conclusion-Patients with at least one chronic condition made up 59.5% of adult ED visits. These data provide national estimates of ED visits by the number and type of chronic conditions in the adult population pre-COVID-19. Given that the presence of chronic conditions increases the risk of hospital admission among patients with COVID-19, these data may represent a useful baseline to quantify prevalence and association of chronic conditions associated with COVID-19 with hospitalization experience and outcomes.

A Meta-analysis of the Impact of COVID-19 on Stroke Mortality

Background The COVID-19 pandemic seriously affects human health and life. COVID-19 has been reportedly associated with a high risk of thrombotic events, which are closely associated with stroke. Objective To assess the effect and possible mechanism of COVID-19 on stroke morbidity, providing a reliable theoretical basis for scientific prevention and treatment of COVID-19 in stroke. Methods We searched databases of Web of Science, PubMed, EmBase, Cochrane Library, CNKI and Wanfang Data for cohort studies and case-control studies related to COVID-19 and stroke published from December 2019 to January 2022. Two researchers conducted literature screening and data extraction separately. The Newcastle-Ottawa Scale was used to assess the quality of included studies. Meta-analysis was used to evaluate the impact of COVID-19 on stroke mortality. Funnel plot was used to evaluate the potential publication bias. Results A total of 18 studies were included, 12 of them were of good quality, and other 6 were of fair quality. Meta-analysis showed that stroke patients with COVID-19 had higher mortality 〔RR=4.16, 95%CI(2.82, 6.13), P<0.000 01〕, prolonged prothrombin time (PT) 〔MD=0.78, 95%CI (0.35, 1.20), P=0.000 3〕, higher D-dimer level 〔MD=1.34, 95%CI(0.83, 1.84), P<0.000 01〕 and higher NIHSS score 〔MD=6.66, 95%CI (4.54, 8.79), P<0.000 01〕, as well as younger age 〔MD=-2.04, 95%CI(-3.48, -0.61), P=0.005〕 than those without COVID-19. There was no statistically significant difference in activated partial thromboplastin time between stroke patients with and without COVID-19 〔MD=2.51, 95%CI(-2.69, 7.71), P=0.34〕. Funnel plot assessing potential publication bias in the impact of COVID-19 on stroke mortality was basically symmetrical. Conclusion COVID-19 could increase the risk of stroke mortality, which may be related to alterations in the coagulation system manifested by abnormal PT and D-dimer level and so on. And the outcomes of stroke patients with COVID-19 were associated with age and NIHSS score at admission. © 2023 Chinese General Practice. All rights reserved.

A Meta-analysis of the Impact of COVID-19 on Stroke Mortality

Background The COVID-19 pandemic seriously affects human health and life. COVID-19 has been reportedly associated with a high risk of thrombotic events, which are closely associated with stroke. Objective To assess the effect and possible mechanism of COVID-19 on stroke morbidity, providing a reliable theoretical basis for scientific prevention and treatment of COVID-19 in stroke. Methods We searched databases of Web of Science, PubMed, EmBase, Cochrane Library, CNKI and Wanfang Data for cohort studies and case-control studies related to COVID-19 and stroke published from December 2019 to January 2022. Two researchers conducted literature screening and data extraction separately. The Newcastle-Ottawa Scale was used to assess the quality of included studies. Meta-analysis was used to evaluate the impact of COVID-19 on stroke mortality. Funnel plot was used to evaluate the potential publication bias. Results A total of 18 studies were included, 12 of them were of good quality, and other 6 were of fair quality. Meta-analysis showed that stroke patients with COVID-19 had higher mortality 〔RR=4.16, 95%CI(2.82, 6.13), P<0.000 01〕, prolonged prothrombin time (PT) 〔MD=0.78, 95%CI (0.35, 1.20), P=0.000 3〕, higher D-dimer level 〔MD=1.34, 95%CI(0.83, 1.84), P<0.000 01〕 and higher NIHSS score 〔MD=6.66, 95%CI (4.54, 8.79), P<0.000 01〕, as well as younger age 〔MD=-2.04, 95%CI(-3.48, -0.61), P=0.005〕 than those without COVID-19. There was no statistically significant difference in activated partial thromboplastin time between stroke patients with and without COVID-19 〔MD=2.51, 95%CI(-2.69, 7.71), P=0.34〕. Funnel plot assessing potential publication bias in the impact of COVID-19 on stroke mortality was basically symmetrical. Conclusion COVID-19 could increase the risk of stroke mortality, which may be related to alterations in the coagulation system manifested by abnormal PT and D-dimer level and so on. And the outcomes of stroke patients with COVID-19 were associated with age and NIHSS score at admission. © 2023 Chinese General Practice. All rights reserved.

COVID-19 vaccination in patients with multiple sclerosis receiving disease-modifying therapies: pragmatic issues.

The SARS-COV-2 pandemic has been a global public health problem since 2019, with over 400 million reported cases, 6 million deaths, and significant economic and social damage. Overlapping SARS-CoV-2 infection in patients with chronic diseases, such as multiple sclerosis (MS), causes management problems, especially in patients treated with disease-modifying therapies. Studies investigating COVID-19 vaccination effectiveness have shown variability in postvaccination immune response that depends on the patient's background treatment, and special attention is required for anti-CD20 therapies. Existing data on the efficacy of COVID-19 vaccination in patients with MS undergoing disease-modifying treatment are summarized and critically evaluated in this article.

[An analysis of clinical and laboratory characteristics of patients with ischemic stroke and COVID-19]. / Analiz kliniko-laboratornykh kharakteristik patsientov s ishemicheskim insul'tom, assotsiirovannym s COVID-19.

OBJECTIVE: To analyze clinical and laboratory characteristics of patients with ischemic stroke associated with COVID-19. MATERIAL AND METHODS: A retrospective analysis of all cases of COVID-19, including those complicated with ischemic stroke, admitted to the multispecialty infectious hospital in Ufa (Russia) in 2020, was performed. Multivariate analysis was used to identify the independent predictors of the development of ischemic stroke in patients with COVID-19. RESULTS: Eleven thousand forty hundred and thirty-two patients were admitted to the multidisciplinary infectious hospital during 2020, 1226 of them also suffered from ischemic stroke. Independent predictors of ischemic stroke in COVID-19 included age and laboratory parameters: increase in number of leucocytes, erythrocytes and platelets, increase of the level of creatinine, glucose, total bilirubin and decrease of the level of total protein, and activated partial thromboplastin time. CONCLUSION: Elderly people, patients with prominent systemic inflammatory response, which presented with leukocytosis, hypercoagulation, multiorgan failure of different severity and hypoproteinemia, were at higher risk of the development of ischemic stroke in COVID-19.

Spectrum of Neurological Complications Following COVID-19 Vaccination in India.

BACKGROUND AND PURPOSE: According to WHO statistics, approximately 6.9 billion people worldwide had been vaccinated against SARS-CoV-2 as at October 27, 2021, including around 1.0 billion people in India. Most Indian recipients received the Covishield (ChAdOx1-S/nCoV-19) vaccine, followed by the Covaxin (an inactivated SARS-CoV-2 antigen) vaccine. This study was conducted to characterize the neurological phenotypic spectrum of patients with adverse events following immunization with any of the available COVID-19 vaccines in India (Covishield or Covaxin) during the study period and their temporal relationship with vaccination. METHODS: This ambispective multicenter hospital-based cohort study covered the period from March to October 2021. The study included all cases suspected of having neurological complications following COVID-19 vaccination. RESULTS: We report a spectrum of serious postvaccination neurological complications comprising primary central nervous system demyelination (4 cases), cerebral venous thrombosis (3 cases), Guillain-Barre syndrome (2 cases), vaccine-induced prothrombotic immune thrombocytopenia syndrome (2 cases), cranial nerve palsies (2 cases), primary cerebral hemorrhage (1 case), vestibular neuronitis (1 case), chronic inflammatory demyelinating polyneuropathy (1 case), generalized myasthenia (1 case), and seizures (1 case). CONCLUSIONS: Although the benefits of vaccination far outweigh its risks, clinicians must be aware of possible serious adverse events associated with COVID-19 vaccinations.

Clinical spectrum of neurological manifestations in pediatric COVID-19 and MIS-C in a Tertiary Care Center, Karnataka, India: a retrospective cross-sectional study

Objective: To study the clinical spectrum of neurological manifestations in Pediatric COVID-19 and MIS-C cases presented to tertiary care hospital. Study design: A Retrospective Cross-sectional study. Study population: All pediatric cases in the age group =14 years diagnosed to be COVID-19 positive or with MIS-C. Methods and Results: The study includes admitted cases of 29 out of 1577 diagnosed COVID-19 children and 13 MIS-C cases;data collected from records from medical record section. Among these 5 cases (17.2%) of COVID-19 and 7 cases (53.8%) of MIS-C presented with various neurological manifestations including convulsion, altered sensorium/behavior and stroke like features.

Acute ischemic stroke in COVID-19: a case-based systematic review

In patients with acute ischemic stroke and COVID-19, the highest ratio between neutrophils and lymphocytes and increased serum levels of C-reactive protein, ferritin, D-dimer and fibrinogen are associated with poor neurological prognosis;75% of these patients die or survive with significant disability. At the moment, however, they cannot be established firm conclusions about the long-term evolution of these patients. Thus, the objective of this systematic review was to identify and correlate clinical and biochemical findings in patients with infection confirmed by SARS-CoV-2 and acute ischemic stroke.

Brain damage in COVID-19. Case reports and summary of data in literature

SARS-CoV-2 (severe acute respiratory syndrome), rapidly escalated to a pandemic and has a significant impact on the quality of human life and activity, affecting millions of people. The presentation resumes data regarding the neurological impairment of patients affected by COVID-19;although the data was observational and limited, this examination would help us to broaden our understanding on the association between COVID-19 and the stroke. In order to support such observations I will present two cases of patients diagnosed with COVID-19 that have shown neurological damage, but with different altogether outcomes. The first case analysed, the age and comorbidities of the patient determined an unfavourable evolution, partly also due to tardiness in getting admitted. The apparition of the stroke after the serological negative bias SARS-CoV-2 denotes the complications recently emerged after the severe infection with COV-2, therefore while the viral infection remitted, the physical and pathological tumult determined the emergence of complications with unfavourable evolution. Although similar in certain ways to the first case, the second patient that also presented multiple unfavourable factors, such as old age, severe comorbidities and beyond that - multiple hospital admissions, recent neurosurgical intervention- clinical, immune-serum and biological evolutions have been favourable. Cerebrovascular events are somewhat common findings in COVID-19 infected patients and they could bare a multifactorial etiology. In order to better understand the impact of cerebrovascular events in COVID-19 infection, more precise and prospective data are needed.

Timing of headache after COVID-19 vaccines and its association with cerebrovascular events: An analysis of 41,700 VAERS reports.

BACKGROUND: Delayed-onset of headache seems a specific feature of cerebrovascular events after COVID-19 vaccines. METHODS: All consecutive events reported to the United States Vaccine Adverse Reporting System following COVID-19 vaccines (1 January to 24 June 2021), were assessed. The timing of headache onset post-vaccination in subjects with and without concomitant cerebrovascular events, including cerebral venous thrombosis, ischemic stroke, and intracranial haemorrhage was analysed. The diagnostic accuracy in predicting concurrent cerebrovascular events of the guideline- proposed threshold of three-days from vaccination to headache onset was evaluated. RESULTS: There were 314,610 events following 306,907,697 COVID-19 vaccine doses, including 41,700 headaches, and 178/41,700 (0.4%) cerebrovascular events. The median time between the vaccination and the headache onset was shorter in isolated headache (1 day vs. 4 (in cerebral venous thrombosis), 3 (in ischemic stroke), or 10 (in intracranial hemorrhage) days, all P < 0.001). Delayed onset of headache had an area under the curve of 0.83 (95% CI: 0.75-0.97) for cerebral venous thrombosis, 0.70 (95% CI: 0.63-76) for ischemic stroke and 0.76 (95% CI: 0.67-84) for intracranial hemorrhage, and >99% negative predictive value. CONCLUSION: Headache following COVID-19 vaccination occurs within 1 day and is rarely associated with cerebrovascular events. Delayed onset of headache 3 days post-vaccination was an accurate diagnostic biomarker for the occurrence of a concomitant cerebrovascular events.

Patients with hypercoagulability and cerebral infarction caused by COVID-19

Corona Virus Disease 19 (COVID-19) plague is a deadly disease that gets the world's attention, also in Indonesia. The death cases report shows a high number with a sum of more than 95.723 in August 2021 and predicted the case will increase. The virus can cause cerebral edema which penetrates the brain through the olfactory epithelium and induces Cytokine Storm Syndrome (CSS) which can cause interference with the Blood-Brain Barrier (BBB) resulting in hypoxia and coagulopathy. This study used a case study approach with detail testing towards one event. In this case, cerebral infarction caused by COVID-19 was proven by laboratory results with symptoms of inflammation, CSF, sepsis, and coagulopathy. These symptoms can lead to cerebral infarction and hypercoagulability. Treatment interventions are carried out to reduce inflammation and cerebral edema and prevent secondary infection. COVID-19, in this case, is considered to have a deleterious effect on cerebral infarction patients. Proper treatments are needed to give better results.

Shared genetic background between SARS-CoV-2 infection and large artery stroke.

BACKGROUND AND AIMS: Increased risk of stroke, particularly large artery stroke (LAS), has been observed in patients with COVID-19. The biological processes underlying the observed higher risk are still unknown. We explored the association between stroke subtypes and COVID-19 susceptibility to understand whether biological mechanisms specific to SARS-CoV-2 uptake/infection could be leading to excess stroke risk in this population. PATIENTS AND METHODS: We constructed a polygenic risk score (PRS) of COVID-19 susceptibility and tested its association with stroke subtypes using individual- and summary-level genetic data (SiGN, MEGASTROKE). We generated co-expression networks of genes involved in SARS-CoV-2 uptake/infection (ACE2, TMPRSS2, BEST3, ISLR2 and ADAM17) based on existing tissue expression libraries. Gene-based association testing was performed using S-PrediXcan and VEGAS2. Permutation independence tests were performed to assess SARS-CoV-2-related gene enrichment in stroke and its subtypes. RESULTS: Our PRS demonstrated an association between COVID-19 susceptibility and LAS in SiGN (OR = 1.05 per SD increase, 95% CI: (1.00, 1.10), p = 0.04) and MEGASTROKE (ß = 0.510, 95% CI: (0.242, 0.779), FDR-p = 0.0019). The SARS-CoV-2 risk-related ISLR2 co-expression gene network was significantly associated with genetic risk of LAS in aorta, tibial arteries, and multiple brain regions (P < 0.05). CONCLUSION: Presence of genetic correlation and significant pathway enrichment suggest that increases in LAS risk reported in COVID-19 patients may be intrinsic to the viral infection, rather than a more generalized response to severe illness.