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1.
J Stroke Cerebrovasc Dis ; 30(12): 106121, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1415617

ABSTRACT

BACKGROUND: There is little information regarding the safety of intravenous tissue plasminogen activator (IV-tPA) in patients with stroke and COVID-19. METHODS: This multicenter study included consecutive stroke patients with and without COVID-19 treated with IV-tPA between February 18, 2019, to December 31, 2020, at 9 centers participating in the CASCADE initiative. Clinical outcomes included modified Rankin Scale (mRS) at hospital discharge, in-hospital mortality, the rate of hemorrhagic transformation. Using Bayesian multiple regression and after adjusting for variables with significant value in univariable analysis, we reported the posterior adjusted odds ratio (OR, with 95% Credible Intervals [CrI]) of the main outcomes. RESULTS: A total of 545 stroke patients, including 101 patients with COVID-19 were evaluated. Patients with COVID-19 had a more severe stroke at admission. In the study cohort, 85 (15.9%) patients had a hemorrhagic transformation, and 72 (13.1%) died in the hospital. After adjustment for confounding variables, discharge mRS score ≥2 (OR: 0.73, 95% CrI: 0.16, 3.05), in-hospital mortality (OR: 2.06, 95% CrI: 0.76, 5.53), and hemorrhagic transformation (OR: 1.514, 95% CrI: 0.66, 3.31) were similar in COVID-19 and non COVID-19 patients. High-sensitivity C reactive protein level was a predictor of hemorrhagic transformation in all cases (OR:1.01, 95%CI: 1.0026, 1.018), including those with COVID-19 (OR:1.024, 95%CI:1.002, 1.054). CONCLUSION: IV-tPA treatment in patients with acute ischemic stroke and COVID-19 was not associated with an increased risk of disability, mortality, and hemorrhagic transformation compared to those without COVID-19. IV-tPA should continue to be considered as the standard of care in patients with hyper acute stroke and COVID-19.


Subject(s)
COVID-19/complications , Fibrinolytic Agents/administration & dosage , Ischemic Stroke/drug therapy , Thrombolytic Therapy , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/mortality , Disability Evaluation , Europe , Female , Fibrinolytic Agents/adverse effects , Hospital Mortality , Humans , Infusions, Intravenous , Intracranial Hemorrhages/chemically induced , Iran , Ischemic Stroke/complications , Ischemic Stroke/diagnosis , Ischemic Stroke/mortality , Male , Middle Aged , Risk Assessment , Risk Factors , Thrombolytic Therapy/adverse effects , Thrombolytic Therapy/mortality , Time Factors , Treatment Outcome
3.
J Neurol ; 268(10): 3549-3560, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1092677

ABSTRACT

BACKGROUND: Since the emergence of COVID-19 pandemic, several cases of cerebral venous sinus thrombosis (CVST) have been reported in SARS-CoV-2 infected individuals. METHODS: Consecutive patients with documented SARS-CoV-2 infection, as well as clinical and radiological characteristics of CVST, were reported from three teaching hospitals in the South West, North West, and the center of Iran between June and July 2020. We also searched the abstract archives until the end of August 2020 and gathered 28 reported cases. The diagnostic criteria for SARS-CoV-2 infection were determined according to SARS-CoV-2 detection in oropharyngeal or nasopharyngeal samples in clinically suspected patients. Demographics, prominent COVID-19 symptoms, confirmatory tests for SARS-CoV-2 infection diagnosis, the interval between the diagnosis of SARS-CoV-2 infection and CVST, clinical and radiological features of CVST, therapeutic strategies, CVST outcomes, rate of hemorrhagic transformation, and mortality rate were investigated. RESULTS: Six patients (31-62 years-old) with confirmed CVST and SARS-CoV-2 infection were admitted to our centers. Four patients had no respiratory symptoms of SARS-CoV-2 infection. Five patients developed the clinical manifestations of CVST and SARS-CoV-2 infection simultaneously. Three patients had known predisposing factors for CVST. Despite receiving CVST and SARS-CoV-2 infection treatments, four patients died. SARS-COV-2 associated CVST patients were older (49.26 vs. 37.77 years-old), had lower female/male ratio (1.42 vs. 2.19), and higher mortality rate (35.29% vs. 6.07%) than CVST not associated with COVID-19. CONCLUSIONS: The role of SARS-CoV-2 as a "cause" versus an "additive contributor" remains to be elucidated. Practitioners should be aware of the possibility of CVST in SARS-CoV-2 infection.


Subject(s)
COVID-19 , Sinus Thrombosis, Intracranial , Adult , Female , Humans , Male , Middle Aged , Pandemics , Research , SARS-CoV-2 , Sinus Thrombosis, Intracranial/complications , Sinus Thrombosis, Intracranial/diagnostic imaging , Sinus Thrombosis, Intracranial/epidemiology
4.
Annu Rev Pharmacol Toxicol ; 2021 Feb 19.
Article in English | MEDLINE | ID: covidwho-1090829

ABSTRACT

In December 2019, a novel coronavirus crossed species barriers to infect humans and was effectively transmitted from person to person, leading including vaccines and antiviral drugs that could prevent or limit the burden or transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health priority. It is thus of utmost importance to assess possible therapeutic strategies against SARS-CoV-2 using experimental models that recapitulate aspects of the human disease. Here, we review available models currently being developed and used to study SARS-CoV-2 infection and highlight their application to screen potential therapeutic approaches, including repurposed antiviral drugs and vaccines. Each identified model provides a valuable insight into SARS-CoV-2 cellular tropism, replication kinetics, and cell damage that could ultimately enhance understanding of SARS-CoV-2 pathogenesis and protective immunity. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 62 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

5.
J Stroke Cerebrovasc Dis ; 30(1): 105454, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1023683

ABSTRACT

OBJECTIVES: COVID-19 disproportionately affects older adults and individuals with cardiovascular co-morbidities. This report presents fifteen patients who had COVID-19 respiratory illness followed by cerebrovascular events. MATERIALS AND METHODS: A call by the Iranian Neurological Association gathered cases across the country who developed neurological symptoms attributed to hemorrhagic or ischemic stroke after a definite or probable Covid-19 respiratory illness. Definite cases were those with a typical respiratory illness, positive nasopharyngeal Covid-19 PCR test, and chest CT consistent with Covid-19 infection. Probable cases were defined by a typical respiratory illness, history of contacts with a Covid-19 case, and chest CT characteristic for Covid-19 infection. RESULTS: Fifteen patients (12 men and 3 women) with an age range of 38 to 93 years old (median: 65 years old) were included. Fourteen patients had a first-ever acute ischemic stroke and one patient had a subarachnoid hemorrhage. Eleven patients (73%) had previous cardiovascular comorbidities. The median time between respiratory symptoms and neurological symptoms was seven days (range 1-16 days). Stroke severity in two patients was mild (NIHSS ≤ 6), in six patients moderate (NIHSS: 7-12), and in seven patients severe (NIHSS ≥13). One patient received intravenous tissue plasminogen activator ( IV-tPA) with improved neurological symptoms. Six out of 15 patients (40%) died. All but one of those who survived had significant disability assessed by a modified ranking scale >2. The majority of patients in this case series had vascular risk factors and their stroke was associated with severe disability and death. CONCLUSION: This report highlights the need for further investigation of the links between Covid-19 and cerebrovascular events.


Subject(s)
COVID-19/complications , Cerebrovascular Disorders/etiology , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/mortality , COVID-19/therapy , Cerebrovascular Disorders/diagnosis , Cerebrovascular Disorders/mortality , Cerebrovascular Disorders/therapy , Disability Evaluation , Female , Humans , Iran , Male , Middle Aged , Recovery of Function , Risk Factors , Severity of Illness Index , Thrombolytic Therapy , Treatment Outcome
6.
J Neurol Sci ; 419: 117183, 2020 12 15.
Article in English | MEDLINE | ID: covidwho-1023662

ABSTRACT

BACKGROUND: SARS-CoV-2 induced coagulopathy can lead to thrombotic complications such as stroke. Cerebral venous sinus thrombosis (CVST) is a less common type of stroke which might be triggered by COVID-19. We present a series of CVST cases with SARS-CoV-2 infection. METHODS: In a multinational retrospective study, we collected all cases of CVST in SARS-CoV-2 infected patients admitted to nine tertiary stroke centers from the beginning of the pandemic to June 30th, 2020. We compared the demographics, clinical and radiological characteristics, risk factors, and outcome of these patients with a control group of non-SARS-CoV-2 infected CVST patients in the same seasonal period of the years 2012-2016 from the country where the majority of cases were recruited. RESULTS: A total of 13 patients fulfilled the inclusion criteria (62% women, mean age 50.9 ± 11.2 years). Six patients were discharged with good outcomes (mRS ≤ 2) and three patients died in hospital. Compared to the control group, the SARS-CoV-2 infected patients were significantly older (50.9 versus 36.7 years, p < 0.001), had a lower rate of identified CVST risk factors (23.1% versus 84.2%, p < 0.001), had more frequent cortical vein involvement (38.5% versus 10.5%, p: 0.025), and a non-significant higher rate of in-hospital mortality (23.1% versus 5.3%, p: 0.073). CONCLUSION: CVST should be considered as potential comorbidity in SARS-CoV-2 infected patients presenting with neurological symptoms. Our data suggest that compared to non-SARS-CoV-2 infected patients, CVST occurs in older patients, with lower rates of known CVST risk factors and might lead to a poorer outcome in the SARS-CoV-2 infected group.


Subject(s)
COVID-19/complications , SARS-CoV-2 , Sinus Thrombosis, Intracranial/etiology , Adult , Aged , COVID-19/blood , Female , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Pandemics , Retrospective Studies , Sinus Thrombosis, Intracranial/diagnostic imaging , Tertiary Care Centers/statistics & numerical data , Thrombophilia/etiology
7.
Virus Res ; 294: 198282, 2021 03.
Article in English | MEDLINE | ID: covidwho-1019557

ABSTRACT

Type V and VI CRISPR enzymes are RNA-guided, DNA and RNA-targeting effectors that allow specific gene knockdown. Cas12 and Cas13 are CRISPR proteins that are efficient agents for diagnosis and combating single-stranded RNA (ssRNA) viruses. The programmability of these proteins paves the way for the detection and degradation of RNA viruses by targeting RNAs complementary to its CRISPR RNA (crRNA). Approximately two-thirds of viruses causing diseases contain ssRNA genomes. The Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) has caused the outbreak of the coronavirus disease 2019 (COVID-19), which has infected more than 88 million people worldwide with near 2 million deaths since December 2019. Thus, accurate and rapid diagnostic and therapeutic tools are essential for early detection and treatment of this widespread infectious disease. For us, the CRISPR based platforms seem to be a plausible new approach for an accurate detection and treatment of SARS-CoV-2. In this review, we talk about Cas12 and Cas13 CRISPR systems and their applications in diagnosis and treatment of RNA virus mediated diseases. In continue, the SARS-CoV-2 pathogenicity, and its conventional diagnostics and antivirals will be discussed. Moreover, we highlight novel CRISPR based diagnostic platforms and therapies for COVID-19. We also discuss the challenges of diagnostic CRISPR based platforms as well as clarifying the proposed solution for high efficient selective in vivo delivery of CRISPR components into SARS-CoV-2-infected cells.


Subject(s)
COVID-19/drug therapy , CRISPR-Cas Systems , SARS-CoV-2/drug effects , SARS-CoV-2/isolation & purification , Antiviral Agents/therapeutic use , COVID-19/diagnosis , COVID-19/therapy , COVID-19 Nucleic Acid Testing , CRISPR-Associated Proteins/therapeutic use , Clustered Regularly Interspaced Short Palindromic Repeats/genetics , Humans , RNA, Guide/genetics , RNA, Guide/metabolism , RNA, Viral/genetics , RNA, Viral/metabolism , SARS-CoV-2/genetics
9.
J Stroke Cerebrovasc Dis ; 29(12): 105321, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-872317

ABSTRACT

BACKGROUND: The emergence of the COVID-19 pandemic has significantly impacted global healthcare systems and this may affect stroke care and outcomes. This study examines the changes in stroke epidemiology and care during the COVID-19 pandemic in Zanjan Province, Iran. METHODS: This study is part of the CASCADE international initiative. From February 18, 2019, to July 18, 2020, we followed ischemic and hemorrhagic stroke hospitalization rates and outcomes in Valiasr Hospital, Zanjan, Iran. We used a Bayesian hierarchical model and an interrupted time series analysis (ITS) to identify changes in stroke hospitalization rate, baseline stroke severity [measured by the National Institutes of Health Stroke Scale (NIHSS)], disability [measured by the modified Rankin Scale (mRS)], presentation time (last seen normal to hospital presentation), thrombolytic therapy rate, median door-to-needle time, length of hospital stay, and in-hospital mortality. We compared in-hospital mortality between study periods using Cox-regression model. RESULTS: During the study period, 1,026 stroke patients were hospitalized. Stroke hospitalization rates per 100,000 population decreased from 68.09 before the pandemic to 44.50 during the pandemic, with a significant decline in both Bayesian [Beta: -1.034; Standard Error (SE): 0.22, 95% CrI: -1.48, -0.59] and ITS analysis (estimate: -1.03, SE = 0.24, p < 0.0001). Furthermore, we observed lower admission rates for patients with mild (NIHSS < 5) ischemic stroke (p < 0.0001). Although, the presentation time and door-to-needle time did not change during the pandemic, a lower proportion of patients received thrombolysis (-10.1%; p = 0.004). We did not see significant changes in admission rate to the stroke unit and in-hospital mortality rate; however, disability at discharge increased (p < 0.0001). CONCLUSION: In Zanjan, Iran, the COVID-19 pandemic has significantly impacted stroke outcomes and altered the delivery of stroke care. Observed lower admission rates for milder stroke may possibly be due to fear of exposure related to COVID-19. The decrease in patients treated with thrombolysis and the increased disability at discharge may indicate changes in the delivery of stroke care and increased pressure on existing stroke acute and subacute services. The results of this research will contribute to a similar analysis of the larger CASCADE dataset in order to confirm findings at a global scale and improve measures to ensure the best quality of care for stroke patients during the COVID-19 pandemic.


Subject(s)
Brain Ischemia/therapy , COVID-19 , Hospitalization/trends , Intracranial Hemorrhages/therapy , Outcome and Process Assessment, Health Care/trends , Stroke/therapy , Thrombolytic Therapy/trends , Time-to-Treatment/trends , Aged , Aged, 80 and over , Bayes Theorem , Brain Ischemia/diagnosis , Brain Ischemia/mortality , COVID-19/epidemiology , Female , Hospital Mortality/trends , Humans , Interrupted Time Series Analysis , Intracranial Hemorrhages/diagnosis , Intracranial Hemorrhages/mortality , Iran/epidemiology , Length of Stay/trends , Male , Middle Aged , Recovery of Function , Stroke/diagnosis , Stroke/mortality , Time Factors , Treatment Outcome
10.
Galen Med J ; 9: e1915, 2020.
Article in English | MEDLINE | ID: covidwho-705482

ABSTRACT

Background: Neurological manifestations and complications are common in viral infections, and they are significant sources for clinical deterioration and poor clinical outcomes. Case report: The current report presents a 38year-old man with Covid-19 respiratory illness who subsequently developed neurological complications and clinical worsening leading to death. This patient sought medical attention after five days of progressive cough, fever, and dyspnea. On arrival in the emergency room, he was found to have hypoxic respiratory failure resulting in intubation and intensive care unit (ICU) admission. Chest CT scan was characteristic for Covid-19 infection, and PCR test on tracheal samples confirmed the diagnosis. On day nine of admission, he developed generalized tonic colonic seizure associated with deterioration of mental status and hemiparesis. Repeated brain CT scans showed subcortical hypoattenuation with associated sulcal effacement in the left occipital and posterior parietal lobes concerning for ischemic changes. The patient passed away on day 17 despite supportive measures. Conclusion: This observation and recent evidence on Covid-19 CNS involvement highlight the need for further studies on early recognition of neurological complications in Covid-19 patients.

11.
12.
Ther Clin Risk Manag ; 16: 595-605, 2020.
Article in English | MEDLINE | ID: covidwho-646401

ABSTRACT

Stroke has been considered as one of the underlying diseases that increases the probability of severe infection and mortality. Meanwhile, there are ongoing reports of stroke subsequent to COVID-19 infection. In this narrative paper, we reviewed major neurologic adverse drug reactions (ADRs) and pharmacokinetics of drugs which are routinely used for COVID-19 infection and their potential drug-drug interactions (PDDIs) with common drugs used for the treatment of stroke. It is highly recommended to monitor patients on chloroquine (CQ), hydroxychloroquine (HCQ), antiviral drugs, and/or corticosteroids about initiation or progression of cardiac arrhythmias, delirium, seizure, myopathy, and/or neuropathy. In addition, PDDIs of anti-COVID-19 drugs with tissue plasminogen activator (tPA), anticoagulants, antiaggregants, statins, antihypertensive agents, and iodine-contrast agents should be considered. The most dangerous PDDIs were interaction of lopinavir/ritonavir or atazanavir with clopidogrel, prasugrel, and new oral anticoagulants (NOACs).

14.
Am J Emerg Med ; 38(7): 1548.e5-1548.e7, 2020 07.
Article in English | MEDLINE | ID: covidwho-232585

ABSTRACT

OBJECTIVE: To present guidance for clinicians caring for adult patients with acuteischemic stroke with confirmed or suspected COVID-19 infection. METHODS: The summary was prepared after review of systematic literature reviews,reference to previously published stroke guidelines, personal files, and expert opinionby members from 18 countries. RESULTS: The document includes practice implications for evaluation of stroke patientswith caution for stroke team members to avoid COVID-19 exposure, during clinicalevaluation and conduction of imaging and laboratory procedures with specialconsiderations of intravenous thrombolysis and mechanical thrombectomy in strokepatients with suspected or confirmed COVID-19 infection. RESULTS: Conclusions-The summary is expected to guide clinicians caring for adult patientswith acute ischemic stroke who are suspected of, or confirmed, with COVID-19infection.


Subject(s)
Brain Ischemia/therapy , Coronavirus Infections/complications , Infection Control , Pneumonia, Viral/complications , Stroke/therapy , Betacoronavirus , Brain Ischemia/diagnostic imaging , COVID-19 , Disease Management , Humans , Pandemics , SARS-CoV-2 , Stroke/diagnostic imaging
15.
J Stroke Cerebrovasc Dis ; 29(9): 104938, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-210006

ABSTRACT

BACKGROUND AND PURPOSE: The novel severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), now named coronavirus disease 2019 (COVID-19), may change the risk of stroke through an enhanced systemic inflammatory response, hypercoagulable state, and endothelial damage in the cerebrovascular system. Moreover, due to the current pandemic, some countries have prioritized health resources towards COVID-19 management, making it more challenging to appropriately care for other potentially disabling and fatal diseases such as stroke. The aim of this study is to identify and describe changes in stroke epidemiological trends before, during, and after the COVID-19 pandemic. METHODS: This is an international, multicenter, hospital-based study on stroke incidence and outcomes during the COVID-19 pandemic. We will describe patterns in stroke management, stroke hospitalization rate, and stroke severity, subtype (ischemic/hemorrhagic), and outcomes (including in-hospital mortality) in 2020 during COVID-19 pandemic, comparing them with the corresponding data from 2018 and 2019, and subsequently 2021. We will also use an interrupted time series (ITS) analysis to assess the change in stroke hospitalization rates before, during, and after COVID-19, in each participating center. CONCLUSION: The proposed study will potentially enable us to better understand the changes in stroke care protocols, differential hospitalization rate, and severity of stroke, as it pertains to the COVID-19 pandemic. Ultimately, this will help guide clinical-based policies surrounding COVID-19 and other similar global pandemics to ensure that management of cerebrovascular comorbidity is appropriately prioritized during the global crisis. It will also guide public health guidelines for at-risk populations to reduce risks of complications from such comorbidities.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/epidemiology , Hospitalization/trends , Pneumonia, Viral/epidemiology , Practice Patterns, Physicians'/trends , Stroke/epidemiology , Stroke/therapy , COVID-19 , Comorbidity , Coronavirus Infections/diagnosis , Coronavirus Infections/mortality , Coronavirus Infections/virology , Healthcare Disparities/trends , Hospital Mortality/trends , Host-Pathogen Interactions , Humans , Incidence , Interrupted Time Series Analysis , Pandemics , Pneumonia, Viral/diagnosis , Pneumonia, Viral/mortality , Pneumonia, Viral/virology , Prospective Studies , Registries , Retrospective Studies , Risk Factors , SARS-CoV-2 , Stroke/diagnosis , Stroke/mortality , Time Factors , Treatment Outcome
16.
Int J Stroke ; 15(5): 540-554, 2020 07.
Article in English | MEDLINE | ID: covidwho-155280

ABSTRACT

BACKGROUND AND PURPOSE: On 11 March 2020, World Health Organization (WHO) declared the COVID-19 infection a pandemic. The risk of ischemic stroke may be higher in patients with COVID-19 infection similar to those with other respiratory tract infections. We present a comprehensive set of practice implications in a single document for clinicians caring for adult patients with acute ischemic stroke with confirmed or suspected COVID-19 infection. METHODS: The practice implications were prepared after review of data to reach the consensus among stroke experts from 18 countries. The writers used systematic literature reviews, reference to previously published stroke guidelines, personal files, and expert opinion to summarize existing evidence, indicate gaps in current knowledge, and when appropriate, formulate practice implications. All members of the writing group had opportunities to comment in writing on the practice implications and approved the final version of this document. RESULTS: This document with consensus is divided into 18 sections. A total of 41 conclusions and practice implications have been developed. The document includes practice implications for evaluation of stroke patients with caution for stroke team members to avoid COVID-19 exposure, during clinical evaluation and performance of imaging and laboratory procedures with special considerations of intravenous thrombolysis and mechanical thrombectomy in stroke patients with suspected or confirmed COVID-19 infection. CONCLUSIONS: These practice implications with consensus based on the currently available evidence aim to guide clinicians caring for adult patients with acute ischemic stroke who are suspected of, or confirmed, with COVID-19 infection. Under certain circumstances, however, only limited evidence is available to support these practice implications, suggesting an urgent need for establishing procedures for the management of stroke patients with suspected or confirmed COVID-19 infection.


Subject(s)
Brain Ischemia/therapy , Coronavirus Infections/transmission , Pneumonia, Viral/transmission , Stroke/therapy , Betacoronavirus , Brain Ischemia/diagnosis , Brain Ischemia/epidemiology , COVID-19 , Cerebral Angiography , Comorbidity , Computed Tomography Angiography , Coronavirus Infections/blood , Coronavirus Infections/diagnosis , Coronavirus Infections/epidemiology , Disease Management , Health Personnel , Humans , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Magnetic Resonance Angiography , Magnetic Resonance Imaging , Pandemics , Patient Isolators , Perfusion Imaging , Pneumonia, Viral/blood , Pneumonia, Viral/diagnosis , Pneumonia, Viral/epidemiology , Risk , SARS-CoV-2 , Stroke/diagnosis , Stroke/epidemiology , Thrombophilia/blood , Tomography, X-Ray Computed
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