 PART 9: The long COVID tsunami – what are the neurological implications?  What we have learned and shared in this blog address just some of the mysteries of long COVID. Given the ever-growing need to better understand the mechanisms and the impact of even more virus variants now, it’s critical to expand our knowledge in order to most appropriately identify treatment options for each individual.
As many clinicians and scientists alike have noted, never before has humanity faced health challenges of this proportion, as well as the potential for a tsunami of neurodegenerative disease and other health problems affecting millions of people worldwide. We all have experienced a major amount of stress as well as fear since the beginning of the pandemic, including much that has been driven by our 24/7 news cycles. It’s very concerning to realize that this only adds to the potential for deleterious effects on our brain health and supports the need to acquire the most relevant and thorough information so we can move forward together in a positive way. Sometimes, understanding and knowledge is hidden in what can feel like a “fog” so it is more important than ever totruly see the total landscape in front of us. As the fog lifts, we are hopeful that soon we all will learn more and be able to identify more answers – and more hope - for so many patients. In health and healing, Dr. Suzanne Gazda References: Guo P, Benito Ballesteros A, Yeung SP, Liu R, Saha A, Curtis L, Kaser M, Haggard MP and Cheke LG (2022) COVCOG 1: Factors Predicting Physical, Neurological and Cognitive Symptoms in Long COVID in a Community Sample. A First Publication From the COVID and Cognition Study. Front. Aging Neurosci. 14:804922. doi: 10.3389/fnagi.2022.804922 Thompson, E.J., Williams, D.M., Walker, A.J. et al. Long COVID burden and risk factors in 10 UK longitudinal studies and electronic health records. Nat Commun 13, 3528 (2022). https://doi.org/10.1038/s41467-022-30836-0 Boldrini M, Canoll PD, Klein RS. How COVID-19 Affects the Brain. JAMA Psychiatry. 2021;78(6):682–683. doi:10.1001/jamapsychiatry.2021.0500 https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2778090 Matschke J, Lütgehetmann M, Hagel C, et al. Neuropathology of patients with COVID-19 in Germany: a post-mortem case series. Lancet Neurol. 2020;19(11):919-929. doi:10.1016/S1474-4422(20)30308-2. https://pubmed.ncbi.nlm.nih.gov/33031735/ Marshall, M. How COVID-19 can damage the brain. Nature Sept 2020. https://www.nature.com/articles/d41586-020-02599-5 Shanley, J.E., Valenciano, A.F., Timmons, G., Miner, A.E., Kakarla, V., Rempe, T., Yang, J.H., Gooding, A., Norman, M.A., Banks, S.J., Ritter, M.L., Ellis, R.J., Horton, L. and Graves, J.S. (2022), Longitudinal evaluation of neurologic-post acute sequelae SARS-CoV-2 infection symptoms. Ann Clin Transl Neurol, 9: 995-1010. https://doi.org/10.1002/acn3.51578 Lee MH, Perl DP, Nair G, Li W, Maric D, Murray H, Dodd SJ, Koretsky AP, Watts JA, Cheung V, Masliah E, Horkayne-Szakaly I, Jones R, Stram MN, Moncur J, Hefti M, Folkerth RD, Nath A. Microvascular Injury in the Brains of Patients with COVID-19. New England Journal of Medicine, December 30, 2020 DOI: 10.1056/NEJMc2033369. Phetsouphanh, C., Darley, D.R., Wilson, D.B. et al. Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection. Nat Immunol 23, 210–216 (2022). https://doi.org/10.1038/s41590-021-01113-x Mehandru, S., Merad, M. Pathological sequelae of long-haul COVID. Nat Immunol 23, 194–202 (2022). https://doi.org/10.1038/s41590-021-01104-y Ceban F, Ling S, Lui LMW, et al. Fatigue and cognitive impairment in Post-COVID-19 Syndrome: A systematic review and meta-analysis. Brain Behav Immun. 2022;101:93-135. doi:10.1016/j.bbi.2021.12.020 Premraj L, Kannapadi NV, Briggs J, et al. Mid and long-term neurological and neuropsychiatric manifestations of post-COVID-19 syndrome: A meta-analysis. J Neurol Sci. 2022;434:120162. doi:10.1016/j.jns.2022.120162 Warren KN, Beason-Held LL, Carlson O, et al. Elevated Markers of Inflammation Are Associated With Longitudinal Changes in Brain Function in Older Adults. J Gerontol A Biol Sci Med Sci. 2018;73(6):770-778. doi:10.1093/gerona/glx199 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946946/ Najjar, S., Pearlman, D.M., Alper, K. et al. Neuroinflammation and psychiatric illness. J Neuroinflammation 10, 816 (2013). https://doi.org/10.1186/1742-2094-10-43 https://jneuroinflammation.biomedcentral.com/articles/10.1186/1742-2094-10-43 Villa, C et al. Can SARS-CoV-2 Infection Exacerbate Alzheimer’s Disease? An Overview of Shared Risk Factors and Pathogenetic Mechanisms. J. Pers. Med. 2022 Noval Rivas M, Porritt RA, Cheng MH, Bahar I and Arditi M (2022) Multisystem Inflammatory Syndrome in Children and Long COVID: The SARS-CoV-2 Viral Superantigen Hypothesis. Front. Immunol. 13:941009. doi: 10.3389/fimmu.2022.941009 Kell DB, Laubscher GJ, Pretorius E. A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications. Biochem J. 2022;479(4):537-559. doi:10.1042/BCJ20220016 Chen Chen, Spencer R. Haupert, Lauren Zimmermann, Xu Shi, Lars G. Fritsche, Bhramar Mukherjee, Global Prevalence of Post-Coronavirus Disease 2019 (COVID-19) Condition or Long COVID: A Meta-Analysis and Systematic Review, The Journal of Infectious Diseases, 2022;, jiac136, https://doi.org/10.1093/infdis/jiac136 Douaud, G., Lee, S., Alfaro-Almagro, F. et al. SARS-CoV-2 is associated with changes in brain structure in UK Biobank. Nature 604, 697–707 (2022). https://doi.org/10.1038/s41586-022-04569-5 Zoe Swank, Yasmeen Senussi, Galit Alter, David R. Walt. Persistent circulating SARS-CoV-2 spike is associated with post-acute COVID-19 sequelae. medRxiv 2022.06.14.22276401; doi: https://doi.org/10.1101/2022.06.14.22276401 Nunez-Castilla J, Stebliankin V, Baral P, Balbin CA, Sobhan M, Cickovski T, Mondal AM, Narasimhan G, Chapagain P, Mathee K, Siltberg-Liberles J. Potential Autoimmunity Resulting from Molecular Mimicry between SARS-CoV-2 Spike and Human Proteins. Viruses. 2022; 14(7):1415. https://doi.org/10.3390/v14071415 Frontera JA, Yang D, Lewis A, et al. A prospective study of long-term outcomes among hospitalized COVID-19 patients with and without neurological complications. J Neurol Sci. 2021;426:117486. doi:10.1016/j.jns.2021.117486 Hugon J, Msika EF, Queneau M, Farid K, Paquet C. Long COVID: cognitive complaints (brain fog) and dysfunction of the cingulate cortex. J Neurol. 2022;269(1):44-46. doi:10.1007/s00415-021-10655-x Spudich, S., Nath, A. Nervous system consequences of COVID-19. Science. 20 Jan 2022. https://www.science.org/doi/10.1126/science.abm2052 Boldrini M, Canoll PD, Klein RS. How COVID-19 Affects the Brain. JAMA Psychiatry. 2021;78(6):682–683. doi:10.1001/jamapsychiatry.2021.0500 Nabil J. Alkayed and Marilyn J. Cipol. Role of Endothelial Cells and Platelets in COVID-Related Cerebrovascular Events. AHA Journal. June 2022. https://www.ahajournals.org/doi/10.1161/STROKEAHA.122.039971 Myoung Hwa Lee, Daniel P Perl, Joseph Steiner, Nicholas Pasternack, Wenxue Li, Dragan Maric, Farinaz Safavi, Iren Horkayne-Szakaly, Robert Jones, Michelle N Stram, Joel T Moncur, Marco Hefti, Rebecca D Folkerth, Avindra Nath, Neurovascular injury with complement activation and inflammation in COVID-19, Brain, 2022. awac151, https://doi.org/10.1093/brain/awac151 https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awac151/6621999 Rhea, E.M., Logsdon, A.F., Hansen, K.M. et al. The S1 protein of SARS-CoV-2 crosses the blood–brain barrier in mice. Nat Neurosci 24, 368–378 (2021). https://doi.org/10.1038/s41593-020-00771-8/; https://www.nature.com/articles/s41593-020-00771-8 Tetyana P. Buzhdygan, Brandon J. DeOre, Abigail Baldwin-Leclair, Trent A. Bullock, Hannah M. McGary, Jana A. Khan, Roshanak Razmpour, Jonathan F. Hale, Peter A. Galie, Raghava Potula, Allison M. Andrews, Servio H. Ramirez. The SARS-CoV-2 spike protein alters barrier function in 2D static and 3D microfluidic in-vitro models of the human blood–brain barrier, Neurobiology of Disease, Volume 146, 2020, 105131, ISSN 0969-9961, https://doi.org/10.1016/j.nbd.2020.105131 Barhoumi T, Alghanem B, Shaibah H, et al. SARS-CoV-2 Coronavirus Spike Protein-Induced Apoptosis, Inflammatory, and Oxidative Stress Responses in THP-1-Like-Macrophages: Potential Role of Angiotensin-Converting Enzyme Inhibitor (Perindopril). Front Immunol. 2021;12:728896. Published 2021 Sep 20. doi:10.3389/fimmu.2021.728896 Carbone MG, Pagni G, Tagliarini C, Imbimbo BP, Pomara N. Can platelet activation result in increased plasma Aβ levels and contribute to the pathogenesis of Alzheimer's disease?. Ageing Res Rev. 2021;71:101420. doi:10.1016/j.arr.2021.101420 Dunai C, Collie C and Michael BD (2022) Immune-Mediated Mechanisms of COVID-19 Neuropathology. Front. Neurol.13:882905. doi: 10.3389/fneur.2022.882905 https://doi.org/10.3389/fneur.2022.882905 Frank MG, Nguyen KH, Ball JB, et al. SARS-CoV-2 spike S1 subunit induces neuroinflammatory, microglial and behavioral sickness responses: Evidence of PAMP-like properties. Brain Behav Immun. 2022;100:267-277. doi:10.1016/j.bbi.2021.12.007 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8667429/ Anthony Fernández-Castañeda, Peiwen Lu, Anna C. Geraghty, Eric Song, Myoung-Hwa Lee, et al. Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation, Cell, Volume 185, Issue 14, 2022, Pages 2452-2468.e16, ISSN 0092-8674, https://doi.org/10.1016/j.cell.2022.06.008. https://www.sciencedirect.com/science/article/pii/S0092867422007139 Soto C, Estrada LD. Protein Misfolding and Neurodegeneration. Arch Neurol. 2008;65(2):184–189. doi:10.1001/archneurol.2007.56 See also: https://www.scientia.global/dr-david-westaway-misfolding-of-brain-proteins-triggering-neurodegenerative-diseases/ Reiken, S, Sittenfeld, L, Dridi, H, Liu, Y, Liu, X, Marks, AR. Alzheimer's-like signaling in brains of COVID-19 patients. Alzheimer's Dement. 2022; 18: 955– 965. https://doi.org/10.1002/alz.12558 Bruno AM, Huang JY, Bennett DA, Marr RA, Hastings ML, Stutzmann GE. Altered ryanodine receptor expression in mild cognitive impairment and Alzheimer's disease. Neurobiol Aging. 2012;33(5):1001.e1-1001.e10016. doi:10.1016/j.neurobiolaging.2011.03.011 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3160507/ Datta, D, Leslie, SN, Wang, M, et al. Age-related calcium dysregulation linked with tau pathology and impaired cognition in non-human primates. Alzheimer's Dement. 2021; 17: 920– 932. https://doi.org/10.1002/alz.12325 Zhang H, Cao Y, Ma L, Wei Y, Li H. Possible Mechanisms of Tau Spread and Toxicity in Alzheimer's Disease. Front Cell Dev Biol. 2021;9:707268. Published 2021 Jul 28. doi:10.3389/fcell.2021.707268 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355602/ Viral Proteins Help Shuttle Tau Aggregates Among Cells. https://www.alzforum.org/news/research-news/viral-proteins-help-shuttle-tau-aggregates-among-cells Liu, S., Hossinger, A., Heumüller, SE. et al. Highly efficient intercellular spreading of protein misfolding mediated by viral ligand-receptor interactions. Nat Commun 12, 5739 (2021). https://doi.org/10.1038/s41467-021-25855-2 Masaharu Somiya. Comment on “Cutting Edge: Circulating Exosomes with COVID Spike Protein Are Induced by BNT162b2 (Pfizer-BioNTech) Vaccination prior to Development of Antibodies: A Novel Mechanism for Immune Activation by mRNA Vaccines”. The Journal of Immunology. April 15, 2022, 208 (8) 1833; DOI: 10.4049/jimmunol.2101082 Douglas B. Kell, Gert Jacobus Laubscher, Etheresia Pretorius; A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications. Biochem J 25 February 2022; 479 (4): 537–559. doi: https://doi.org/10.1042/BCJ20220016 https://portlandpress.com/biochemj/article/479/4/537/230829/A-central-role-for-amyloid-fibrin-microclots-in Etheresia Pretorius, Chantelle Venter, Gert Jacobus Laubscher et al. Combined triple treatment of fibrin amyloid microclots and platelet pathology in individuals with Long COVID/ Post-Acute Sequelae of COVID-19 (PASC) can resolve their persistent symptoms, 28 December 2021, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-1205453/v1] Additional reading: More details about these or other resources are available upon request, so please let us know if you have questions: https://www.suzannegazdamd.com/blog---long-covid/chronic-lyme-disease-may-have-lessons-about-long-covid https://www.sciencedirect.com/science/article/abs/pii/S1521661616304004 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8860813/ https://www.frontiersin.org/articles/10.3389/fnagi.2017.00402/full https://link.springer.com/article/10.1007/s13760-022-01984-3 https://www.scientificamerican.com/article/white-matter-matters/
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