Vaccine-induced immune thrombotic thrombocytopenia and cerebral venous sinus thrombosis post COVID-19 vaccination; a systematic review.

INTRODUCTION: The common reported adverse effects of COVID-19 vaccination consist of the injection site's local reaction followed by several non-specific flu-like symptoms. However, rare cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) and cerebral venous sinus thrombosis (CVST) after viral vector vaccines (ChAdOx1 nCoV-19 vaccine, Ad26.COV2 vaccine) have been reported. Herein we systemically reviewed the reported cases of CVST and VITT following the COVID-19 vaccination. METHODS: This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We searched PubMed until May 19, 2021, and the following Keywords were used: COVID Vaccine & Neurology, AstraZeneca COVID vaccine, ChAdOx1 nCoV-19 COVID vaccine, AZD1222 COVID vaccine, Janssen COVID vaccine, Johnson & Johnson COVID vaccine, Ad26.COV2 COVID vaccine. The authors evaluated the abstracts and titles of each article for screening and inclusion. English reports about post-vaccine CVST and VITT in humans were collected. RESULTS: Until May 19, we found 877 articles with the searched terms. We found 12 articles, which overall present clinical features of 36 patients with CVST and VITT after the ChAdOx1 nCoV-19 vaccine. Moreover, two articles were noted, which present 13 patients with CVST and VITT after Ad26.COV2 vaccine. The majority of the patients were females. Symptom onset occurred within one week after the first dose of vaccination (Range 4-19 days). Headache was the most common presenting symptom. Intracerebral hemorrhage (ICH) and/or Subarachnoid hemorrhage (SAH) were reported in 49% of the patients. The platelet count of the patients was between 5 and 127 cells×109/l, PF4 IgG Assay and d-Dimer were positive in the majority of the reported cases. Among 49 patients with CVST, at least 19 patients died (39%) due to complications of CVST and VITT. CONCLUSION: Health care providers should be familiar with the clinical presentations, pathophysiology, diagnostic criteria, and management consideration of this rare but severe and potentially fatal complication of the COVID-19 vaccination. Early diagnosis and quick initiation of the treatment may help to provide patients with a more favorable neurological outcome.

Safety and efficacy of antiplatelet use before intravenous thrombolysis for acute Ischemic stroke.

AIM: To study the effects of pretreatment with Antiplatelet (AP) before IV thrombolysis (IVT) on the rate of symptomatic intracranial hemorrhage (sICH) and functional outcome in patients with Acute Ischemic stroke (AIS). METHOD: In this retrospective study, the medical records and cerebrovascular images of all the patients who received IVT for AIS in our center in a 9.6-year period were reviewed. Patients who took at least one dose of any APs in the last 24 h prior to IVT were identified. They were categorized according to the type of AP, single versus dual AP therapy (DAPT), and dose of AP. Rate of sICH and functional outcome at discharge were compared between the AP users and non-users. RESULTS: A total of 834 patients received IVT for AIS in our center during a 9.6- year period. Multivariate models were adjusted for age, NIHSS on admission, history of atrial fibrillation, history of hypertension, INR on admission, history of stroke and diabetes mellitus. In multivariate regression analyses and after adjusting for the variables mentioned above, the use of any AP was not associated with an increased rate of sICH (OR = 1.28 [0.70-2.34], p = 0.425). Furthermore, the use of DAPT did not significantly increase the rate of sICH in multivariate regression analyses. (OR = 0.663 [0.15-2.84], p = 0.580). The patients on any AP had a lower chance of having good functional outcome in univariate analysis (OR = 0.735 [0.552-0.979], p = 0.035). However, when adjusted for age, baseline NIHSS, history of diabetes, hypertension and prior stroke, AP use was not associated with a decreased chance of having a good functional outcome at discharge. (OR = 0.967 [0.690-1.357], p = 0.848). In addition, no significant difference was noted in the rate of good functional outcome between patients on DAPT and no AP users in multivariate regression analyses. (OR = 1.174 [0.612-2.253], p = 0.629). CONCLUSION: Our study did not show any significant association between the risk of sICH and good functional outcome after IVT for AIS patients on AP therapy (dual or single) in comparison with AP naïve patients.

COVID-19 and disease-modifying therapies in patients with demyelinating diseases of the central nervous system: A systematic review.

INTRODUCTION: The Coronavirus disease-19 (COVID-19) pandemic continues to expand across the world. This pandemic has had a significant impact on patients with chronic diseases. Among patients with demyelinating diseases of the central nervous system (CNS), such as Multiple Sclerosis (MS) or Neuromyelitis Optica Spectrum Disorder (NMOSD), concerns remain about the potential impact of COVID-19 on these patients given their treatment with immunosuppressive or immunomodulatory therapies. In this study, we review the existing literature investigating the impact of disease-modifying therapies(DMT) on COVID-19 risks in this group of patients. METHOD: For this systematic review, we searched PubMed from January 1, 2020, to December 3, 2020. The following keywords were used: "COVID-19" AND "Multiple Sclerosis" OR "Neuromyelitis Optica." Articles evaluating COVID-19 in patients with demyelinating diseases of CNS were included. This study evaluates the different aspects of the DMTs in these patients during the COVID-19 era. RESULTS AND CONCLUSION: A total of 262 articles were found. After eliminating duplicates and unrelated research papers, a total of 84 articles met the final inclusion criteria in our study. Overall, the experiences of 2493 MS patients and 37 NMOSD patients with COVID-19 were included in this review. Among them, 46(1.8%) MS patients died(the global death-to-case ratio of Covid-19 was reported about 2.1%). Among DMTs, Rituximab had the highest mortality rate (4%). Despite controversies, especially concerning anti-CD20 monoclonal antibody therapies, a relation between DMT-use and COVID-19 disease- course was not found in many studies. This observation reinforces the recommendation of not stopping current DMTs. Other variables such as age, higher expanded disability status scale (EDSS) scores, cardiac comorbidities, and obesity were independent risk factors for severe COVID-19. Despite the risks of infection, most patients were willing to continue their DMT during the pandemic because of more significant concern about the risk of relapse or worsening MS symptoms. After the infection, an immune response's attenuation was seen in the patients on Fingolimod and anti-CD20 monoclonal antibodies. This may be a critical finding in future vaccinations.