MSc Data Project 2024 - Covid - Long Covid and Stroke PDF

MSc PROJECT: 2024 Systematic data analysis with relevant associated supporting basic science review Dr Michael Leach ([email protected]) 10,000 word target (excluding references). Student AIM: An investigative data evidence analysis of the mechanisms which cause cardiovascular issues and ischemic brai...

MSc PROJECT: 2024 Systematic data analysis with relevant associated supporting basic science review Dr Michael Leach ([email protected]) 10,000 word target (excluding references). Student AIM: An investigative data evidence analysis of the mechanisms which cause cardiovascular issues and ischemic brain stroke following SARS-CoV-2/ Covid 19 infection, plus emerging Long Covid complications. Science targets which give rise to treatment options and relevant clinical trial and treatment data will be evaluated. SARS-CoV-2/Covid-19 infection and stroke. The basics- PRE-Covid-19: Stroke is both a cardiovascular (CV) and neurological event – a cardiovascular event leading to ischemic brain damage!. Approx. 60 cases/100,000/annum. Pre-Covid: 2022- UK population~68.5M. In UK: ~41,000/annum stroke victims. 15M worldwide: over 1/3rd can die. 1 in 4 adults over 25 may experience stroke in their lifetime. Cerebral ischemic stroke can occur due to a blocked blood vessel in the brain (Thrombotic) stroke. OR a burst blood vessel (Haemorrhagic). Stroke brain damage is time determined – through both biochemical and inflammatory mechanisms. Major evolution of critical brain damage from 4 hours to 4 days! “TIME IS BRAIN”. Major risk factor is high blood pressure (there are others) – A RISK FACTOR NOW IS COVID-19 INFECTION!  Literature Statements and Figures available for Covid-19: 600 Million Covid-19 infections as of January 2023! 21% of SARS-CoV-2/Covid-19 patients have both neurological symptoms and thromboembolic events. 7.6 fold increased chance of stroke over and above influenza (avoid both!). 1.3% of ALL Covid-19 patients WORLDWIDE have been stroke victims. January 2022 World data: Covid-19 infection: 328M cases, 5.54M deaths  Approx. 4.3M stroke victims worldwide due to Covid-19 alone! Intensive care unit (ICU) patients with Covid-19: 31% thrombotic complications. Covid-19 is an independent risk factor for stroke in hospitalised patents. Covid-19 induced abnormal blood coagulation/hyper coagulability can lead to stroke (often observed in Covid intravenous cannulated patients).  Covid 19/SARS-CoV-2: pathological mechanisms are MANY!!. 1. Cytokine Storm –proinflammatory cytokines Role of Interleukin-6. IL6 is a drug target. 2. Coagulation dysfunction: triggers coagulation/blood clot pathway. 3. Viral CNS invasion: infects endothelial cells/Blood Brain Barrier. 1. Angiotensin converting enzyme 2 (ACE2) as a viral carrier expressed in heart/blood vessels/ gut/ lung/ kidneys. 2. ACE2 in Brain: on neurons, glial cells, cerebral blood vessel endothelium. 3. Covid-19 binds to ACE2 and “hijacks” to gain CNS entry via ACE2. 4. ACE2 expression 3X higher in adult males to females. Covid related References to help!! Spence JD, et al. Mechanisms of stroke in Covid-19. Cerebrovascular Diseases (2020), Published online July 20, 2020, Karger. DOI: 10.1159/000509581. Fifi JT and Mocco J. Covid-19 related stroke in young individuals. Lancet Neurology (2020), 19, 713-715. Ojo AS, et al. Acute ischemic stroke in Covid-19: Putative mechanisms, clinical characteristics and management. Neurology Research International (2020). Article ID 7397480, 7 pages, Hindawi (https://doi.org/10.1155/2020/7397480) Tang Y et al. Cytokine storm in Covid-19: the current evidence and treatment strategies. Frontiers in Immunology (2020). 11, Article 1708. Published 10th July 2020. Doi:10.3389/fimmu.2020.01708 Xu X. et al. Effective treatment of severe Covid-19 patients with tocilizumab. PNAS (Proceedings National Academy Science), (2020). 117, 10970-10975. (Tocilizumab targets Interleukin-6!! ) Zhang S, et al. Covid-19 and Ischemic stroke: Mechanisms of hypercoagulability. International Journal of Molecular Medicine (2021), 46: 21 Tang X, and Zheng F. A review of ischemic stroke in Covid-19: currently known pathophysiological mechanisms. Neurological Sciences (2021), published online 21 October. https://doi.org/10.1007/s10072-021- 05679-0 Yang L et al. The signal pathways and treatment of cytokine storm in COVID- 19 Signal transduction and targeted therapy (2021), 6, 255. https://doi.org/10.1038/s41392-021-00679-0 Nannoni S et al. Stroke in Covid 19: a systematic review and meta-analysis. International Journal of Stroke (2021). 16(2), 137-149 Andrada B.S. et al. Long-COVID and Post-COVID health complications: An Up- to-date review on clinical conditions and their possible molecular mechanisms. Viruses (2021): 13,700. MDPI (https://doi.org/10.3390/v13040700) Hingorani K.S. et al , COVID-19 and the brain. Trends in Cardiovascular Medicine (2022): 32,323-330. Li G. et al. Therapeutic strategies for COVID-19: progress and lessons learned. Nature Reviews Drug Discovery (2023): 22,449-475. Sherif Z.A. et al. Pathogenic mechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC). (2023): eLIFE 12:e86002. DOI: https://doi.og/10.7554/eLife.86002 Vlaicu S.I. et al. COVID, complement and the brain. (2023): Frontiers in Immunology. Review. 14:1216457. doi: 10.3389/fimmu.2023.1216457 [Krishna B.A et al. Spontaneous, persistent, T-cell-dependent IFN- gamma release in patients who progress to Long Covid. (2024) Science Advances. 10, eadi937 (21 February 2024). ] More useful general articles on cerebral ischemic stroke. Maida CD. et al. Neuroinflammatory mechanisms in ischemic stroke: focus on cardioembolic stroke, background and therapeutic approaches. International Journal Molecular Sciences. (2020), 21, 6454; doi:10.3390/ijms21186454. Khosh ES. et al. Pathogenic mechanisms following ischemic stroke. Neurological Science (2017), 38, 1167-1186. Yang C et al. Neuroinflammatory mechanisms of blood brain barrier damage in ischemic stroke. Am. J. Physiol. Cell Physiol. (2019), 316(2), C135-C153, Patel RAG and McMullen PW. Neuroprotection in the treatment of acute ischemic stroke. Progress in cardiovascular disease (2017), 59, 542-548. Structure: Student AIM: An investigative data analysis of the mechanisms which cause cardiovascular issues and ischemic brain stroke following SARS-CoV-2/ Covid 19 infection, plus emerging Long Covid complications. Science targets which give rise to treatment options and relevant clinical trial and treatment data will be evaluated. Start by searching and make notes plus writing on the cardiovascular issues and cerebral ischemic stroke and what we know and the available treatments before the COVID-19 pandemic occured. Treatment stems from trial data! Look for the data which allowed regulatory approval for patient use! (~30% ). Then focus on new science on Covid 19 induced cardio issues and stroke- what we know (data evidence!) about how the virus enters the brain/ACE2 transport/cytokine storm inflammatory process/hyper- coagulation. EVIDENCED BASED SCIENCE is what points to avenues for intervention and therapies, data obtained, tried and clinically trialled in Covid-19 infected patients. Also :Long Covid- what do we know now (2023/24) and emerging data to guide intervention. (I will help and guide you, but you must read and research first to learn!!). (BUT NOTE: THIS IS NOT AN ESSAY ON VACCINES!) (~70% ) AND FINALLY…………. PLEASE DO NOT RESORT to USING AI!!! I will know! Turnitin score 20 or less please] Recently released statement regarding AI use (faculty of Engineering and Science) - “Students must reference any copying or paraphrasing of AI-generated content. - Using AI without acknowledgment for analysis, evaluation, calculation, or coding is academic misconduct. - Failing to declare AI usage, leading to inflated achievement against assessment criteria, is also misconduct. - Acknowledging AI use in assignments via a declaration appended to assessed work is required.” [Suspected inappropriate AI use is subject to Academic Misconduct Procedure].