As I have discussed in detail in my previous blog in our long COVID series, residual virus is not thought to be the only problem we face relevant to ongoing neurological issues following an infection. Medical News Today reported in a new perspective article, based on clinical observations, autopsies, and lab findings by a team of researchers in Chicago, which argues against the virus directly affecting brain cells. Instead, it appears that the brain is affected by systemic inflammation and circulatory problems.1
I also would add that it is even more complicated than that, as discussed here in “Why does long COVID happen?” https://www.suzannegazdamd.com/blog---long-covid/why-does-long-covid-happen
Researchers are just beginning to piece together how Covid-19 affects the body long-term, but it's clear that the disease causes lasting cognitive impairment and other symptoms in some people, including those who have had mild cases.
History reflects a sharp increase in Parkinson's cases following the 1918 influenza pandemic.
What we are all wondering now is whether we will we see a similar rise in neurodegenerative diseases post COVID.
One published study linked biomarkers indicative of Alzheimer's disease and dementia to those found in recovered Covid patients who experienced cognitive impairment2 while other studies have found that loss of smell appears to be tied to symptoms related to cognitive function.
In this study, patients with mild cognitive impairment were found to have an increased blood level of the three microRNAs and 90 percent developed Alzheimer’s disease (AD) within two years. The study found that on mice and cell cultures, the three microRNAs influence inflammatory processes in the brain and “neuroplasticity,” including the ability of nerve cells to connect to one another. MicroRNAs are molecules that regulate and influence the production of proteins and are a central process in metabolism and there is accumulating evidence which shows that microRNAs play a critical role in the pathogenesis of AD. In this study, it was found that exosomes carry mRNA post vaccine3; so, do we subsequently need to be concerned about the circulating mRNA given the connection to neurodegenerative disease?
Ongoing research continues to identify more neurological concerns.
As I have previously discussed, the UK Biobank studies indicated a loss of cortical brain volume following a COVID infection (see https://www.suzannegazdamd.com/blog---long-covid/long-covid-and-the-brain-what-happens-when-the-storm-passes). And in an October 2021 publication in JAMA Network Open, scientists reported on a data analysis of a cohort study of 740 patients at Mount Sinai Health System during the period of April 2020 to May 2021. They noted “a relatively high frequency of cognitive impairment several months after patients contracted COVID-19.” 4
Now in another new study, published in JAMA Network Open, researchers in Norway found that 12 percent of patients reported continual issues with concentration eight months after they had Covid-19. Eleven percent had ongoing memory problems, leaving clinicians to ponder just how long these effects could last? 5
A study from researchers at Columbia University Vagelos College of Physicians and Surgeons reports that the brains of a small sample of patients who died of COVID display some of the same molecular changes found in the brains of people with Alzheimer’s disease.
In the new study, the Columbia researchers found high levels of phosphorylated tau in the brains of the COVID patients in addition to defective ryanodine receptors.6 Ryanodine receptors (RyRs) are intracellular calcium-release channels found on the endoplasmic reticulum of all cells. This RyR2 remodeling results in intracellular Ca2+ leak, which can play a role in heart failure progression, pulmonary insufficiency, as well as cognitive dysfunction.
Their findings link the inflammatory response to SARS-CoV-2 infection with the neuropathological pathways causing tau hyperphosphorylation typically associated with Alzheimer's. Hyperphosphorylation is one of the signaling mechanisms used by the cell to regulate mitosis, the process by which a cell divides into two identical cells. The study results also point to a role for leaky ryanodine receptor 2 (RyR2) in the pathophysiology of SARS-CoV-2 infection. Alteration of calcium signaling and high levels of oxidative stress are known factors in the pathophysiology of AD.
Alteration of Ca2+ signaling may be particularly crucial in COVID-19-infected patients with cardiovascular/neurological diseases due, in part, to the multifactorial RyR2 remodeling after the cytokine storm, increased TGF-β activation, and increased oxidative stress
In yet another investigation, researchers at the Yale School of Medicine found that susceptible neurons in the prefrontal cortex develop a “leak” in calcium storage with advancing age.7
Neurons run on calcium, which plays a dual role as a charge carrier and an intracellular messenger. Calcium signals regulate various developmental processes and have a key role in apoptosis, neurotransmitter release, and membrane excitability; calcium is also involved in memory formation, metabolism, and cell growth, all of which it makes it a diverse multitasker.
An additional study examined post-COVID symptoms in a small number of Parkinson’s’ patients. Among the symptoms that persisted after COVID infection were worsening of motor function, increased levodopa daily dose requirements, fatigue, cognitive disturbances, and sleep disturbances. Experts believe that in people with Parkinson’s, the molecules of a protein in the brain called alpha-synuclein clump together at the cellular level to form toxic amyloid fibrils. Over time, these kill off the neurons that produce the neurotransmitter dopamine, which is essential for motor control.
For more about alpha-synuclein see: https://www.suzannegazdamd.com/scientifically-speaking1/alpha-synuclein-in-neurodegenerative-disease
Scientists at the University of Twente in Enschede, the Netherlands, have now found evidence that one of the proteins in SARS-CoV-2 may speed up the conversion of alpha-synuclein to amyloid fibrils. Their study, which involved experiments in test tubes using human cell cultures, appears in ACS Chemical Neuroscience.
In a preprint study published at medRxiv.com, researchers aimed to identify a potentially important cluster of similar patient-reported symptoms from individuals diagnosed with post-acute sequelae SARS-CoV-2 infection (PASC). The results showed that patients experiencing PASC exhibit a prolonged and debilitating symptom complex that prominently involves vibrations and tremors. These are also common symptoms that have occurred in some instances following vaccination.
The concern for rising cases of neurodegenerative disease in the wake of COVID-related developments is very real – and we have to wonder if there is indeed a possible “tsunami” to come. As of this writing, according to the website https://vaersanalysis.info/, there are over a million adverse events reported to the Vaccine Adverse Event Reporting System (VAERS), although this may be underrepresented. 8, 9 VAERS is a publicly accessible platform operated by the Centers for Disease Control and Prevention (CDC) to analyze reports of possible vaccine side effects; note that anyone can report an adverse event to VAERS. It’s important to understand that VAERS is a passive reporting system, meaning it relies on individuals to send in reports of their experiences. VAERS is not designed to determine if a vaccine caused a health problem, but is useful for detecting unusual or unexpected patterns of adverse event reporting that might indicate a possible issue with a vaccine. In this way, VAERS can provide health agencies and researchers with valuable information that additional evaluation may be necessary to further assess any possible issues.
Prior to the start of the COVID pandemic, these were once the statistics: five million Americans suffer from Alzheimer's disease; one million from Parkinson's; 400,000 from multiple sclerosis (MS); 30,000 from amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease); and 30,000 from Huntington's disease. Because neurodegenerative diseases strike primarily in mid- to late-life, the incidence is expected to soar as the population ages, which by 2030, will include as many as one in five Americans over age 65. Subsequently, if these trends are left unchecked, it’s entirely possible that 30 years from now, more than 12 million Americans will suffer from neurodegenerative diseases. And that’s without including the potential for increased brain disorders as a result of COVID.
A common feature of neurodegenerative diseases such as Alzheimer’s, Parkinson’s, amyotrophic lateral sclerosis (ALS) and Huntington’s is the formation of clumps of misfolded proteins in the brain. These aggregations fasten around or inside neurons, which find it increasingly difficult to communicate with each other.
The link between neurodegeneration and viral infection is unclear. Direct causation has been suggested by the occurrence of Aβ peptide aggregates in cell lines and in animals infected with herpes simplex and respiratory syncytial virus.
But remember, we have never seen a virus like COVID 19 before. And it’s important to note as well that we have never before employed a vaccine that works in the same manner and forms potentially damaging spike proteins. So, the “unknown” element is worrisome.
The Rising Tide
Before the rollout of the COVID vaccines, we did not fully realize the potential harm of this very dangerous viral fragment, e.g. spike protein.
For more about spike protein, inflammation and COVID see:
Dr. Patterson’s discovery of S 1 protein in circulation monocytes for up to 15 months and high levels of inflammatory cytokines shows us the mechanisms involved in long COVID. His next paper, soon to be in preprint, will show the same phenomena going on in the vaccine injured.
Here are some of my thoughts as to how and why I believe we will see a rise in neurodegenerative disease (NDD) in the coming months and years:
ACE2 receptors act like locks on cells, and the SARS-CoV-2 spike proteins act like keys that open the locks letting the virus enter cells to rapidly multiply. The ACE 2 receptors are all over the body and the brain and these receptors can respond to spike protein alone without any virus present.
SARS-CoV-2 spike protein elicits cell signaling in human host cells.
The SARS-CoV-2 spike protein, a class I viral fusion protein, is critical to initiating the interactions between the virus and the host cell surface receptor, facilitating viral entry into the host cell by assisting in the fusion of the viral and host cell membranes.
The spike protein may also affect the cells of systemic, brain, and coronary vasculatures, eliciting other cardiovascular diseases such as coronary artery disease, systemic hypertension, and stroke. In addition to cardiovascular cells, other cells that express ACE2 have the potential to be affected by the SARS-CoV-2 spike protein, which may cause adverse pathological events.
Multiple other tissues/ organs house ACE 2 receptors besides the cardiovascular system and ACE 2 receptors are found throughout the body in the GI system, kidney, skin, vasculature, , testis, lung (type I and type II alveolar epithelial cells), nasal, and oral mucosa and nasopharynx, and the brain (astrocytes, pericytes, amygdala, cerebral cortex and brainstem, endothelial cells). Studies have shown that spike protein has been shown to damage and cross the blood-brain barrier (BBB). 9. 10
The diagram below shows just how widespread the ACE 2 receptors are throughout the body and brain.
Figure 1. Schematic representation of ACE2 expression in human organs. ACE2 mRNA is present in all organs (28). ACE2 protein expression is present in heart, kidney, testis, lung (type I and type II alveolar epithelial cells), nasal, and oral mucosa and nasopharynx (basal layer of the non-keratinizing squamous epithelium), smooth muscle cells and endothelium of vessels from stomach, small intestine and colon, in smooth muscle cells of the muscularis mucosae and the muscularis propria, in enterocytes of all parts of the small intestine including the duodenum, jejunum, and ileum (but colon), skin (basal cell layer of the epidermis extending to the basal cell layer of hair follicles smooth muscle cells surrounding the sebaceous glands, cells of the eccrine glands), endothelial, and smooth muscle cell of the brain (28). Red asterisk (*): ACE2 deficiency only hypothesized.
Renin Angiotensin System (RAS) also plays an indispensable role in brain function, and studies have demonstrated that renin, ACE, Ang II, and Ang (1-7) are all found in the central nervous system. They participate in the blood pressure regulation, water and food intake, maintenance of the blood–brain barrier, and even movement, learning, memory, and emotional control.
It’s well established that ACE2 plays a regulatory role in neurodegenerative diseases. The level of ACE was decreased in the cerebrospinal fluid of AD patients, and it was negatively correlated with the level of Aβ. So, if we are blocking ACE 2 from spike protein attachment or autoantibodies bind to spike protein, this may well provoke pathophysiological mechanisms to enhance NDD.12, 13, 14 And autoantibodies against ACE2 may develop after SARS-CoV-2 infection or after COVID vaccines and this forms anti-idiotypic antibodies to anti-spike protein antibodies.
Protein misfolding is increased.
SARS-CoV-2 spike protein can form amyloid and toxic aggregates that can act as seeds to aggregate many of the misfolded brain proteins and can ultimately lead to neurodegeneration.
In this study, findings showed how spike protein can induce protein misfolding with the outcome of toxic proteins like tau, alpha synuclein, prion, and amyloid. Heparin-binding site on the S1 might assist the binding of amyloid proteins to the viral surface and subsequently could lead to neurodegeneration in brain.
SARS-CoV-2 spike protein interactions with amyloidogenic proteins: potential clues to neurodegeneration.15
Continuing research has identified, as scientists seek to better understand the evolving health situation, other mechanisms of concern including:
In this study, COVID vaccinations seem to cause a specific amyloid-beta immune-reactivity noted on some PET and CT scans.
An overwhelmed endoplasmic reticulum.
Viral infections typically lead to an increase in protein synthesis that can overwhelm the endoplasmic reticulum (ER) folding capacity, which may result in unfolded protein accumulation and ER stress:
SARS-CoV-2 activates ER stress and Unfolded protein response 2021
Take down of innate immunity.
The innate immune system is the first line of the host defense program against pathogens and harmful substances. Coronaviruses like SARS-CoV-2 have evolved multiple means to evade host antiviral immune responses. In this preprint study in medRxiv, “The BNT162b2 mRNA vaccine against SARS-CoV-2 reprograms both adaptive and innate immune responses” found that the mRNA BNT162b2 vaccine induces complex functional reprogramming of innate immune responses. There is a direct and well established link between the innate immunological systems in neurodegenerative and psychiatric diseases. So, will this alteration in our innate immune system pave the way for rising rates of NDD? 16
Exosomes act as a communication network for cells.
When a cell is under stress, it releases exosomes containing some of the molecules that are stressing it. Exosomes act as intercellular messengers that give the ability to communicate between both cells of the same type and other cell types. So, in the case of the COVID vaccines, the exosomes contain spike protein and microRNA; microRNAs are signaling molecules that are able to influence cell function.
Two microRNAs, miR-148a and miR-590, are excreted in the exosomes along with the spike protein. This significantly disrupts the type-1 interferon response in any cell, including immune cells. Type-1 interferon keeps latent viruses like herpes and varicella (which causes shingles) viruses in check, so if your interferon pathway is suppressed, these latent viruses can also start to emerge. It is vital to have a healthy innate immune system
Over the course of the past year, research groups have detected unusually high levels of autoantibodies, which can attack the body’s own cells and tissues, in people after a SARS-CoV-2 infection. In Nature in May 2021, immunologists Aaron Ring and Akiko Iwasaki at Yale School of Medicine and their colleagues reported finding autoantibodies in acute COVID-19 patients that target the immune system and brain; they are now investigating how long the autoantibodies persist and whether they can damage tissues. This month, Cedars-Sinai Medical Center cardiologist Susan Cheng and protein chemist Justyna Fert-Bober wrote in the Journal of Translational Medicine that autoantibodies could last up to 6 months after infection, although the researchers did not correlate autoantibodies’ persistence with ongoing symptoms.17 Autoantibodies have been implicated in several neurodegenerative diseases.18
Other concerns about spike protein.
SARS-CoV-2 spike protein have the potential to cause microvascular injury to the brain, heart, liver, and kidneys. The association between COVID-19 and blood clots was recognized early in the pandemic among hospitalized COVID-19 patients. Two studies published by JAMA Cardiology in 2021 discuss adverse effects associated with COVID-19 vaccines; one investigation describes vaccine-induced immune thrombotic thrombocytopenia with cerebral venous sinus thrombosis (VITT with CVST) linked to the AstraZeneca/Oxford and Johnson & Johnson vaccines.19 Another study examined the cases of 15 adolescents who experienced short-term myocarditis after receiving the Pfizer/BioNTech vaccine.20
Some researchers are looking at another possible culprit for long COVID: tiny clots in the blood. In an acute SARS-CoV-2 infection, small clots can form that can damage cells that line blood vessels. Resia Pretorius, a physiologist at Stellenbosch University in South Africa, and her colleagues published preliminary evidence in August in Cardiovascular Diabetology that microscopic clots can linger after an infection clears. Data is accumulating that this same phenomenon can happen in some patients after the COVID vaccination.21 There are numerous case reports of stroke, venous thrombosis, blood clots, myocardial infarction and other information that has been submitted to VAERS. Remember, the vaccines can produce the same side effects as the infection because as we have discussed, it is the viral fragment, e.g. the spike protein, which can linger and wreak havoc on the body and the brain.
The soluble spike variants may induce thrombotic events via an antibody-mediated mechanism when binding to ACE2-expressing endothelial cells in blood vessels.22 Other possible causes of thrombosis include spike protein interactions with different C-type lectin receptors, heparin sulfate proteoglycans, and the CD147 receptor. Platelets also become activated for they carry ACE 2 receptors. Binding of the spike protein to platelets can also cause the platelets to become activated; activated platelets tend to clump, which can lead to the formation of clots. There is evidence that the spike protein can interact with other proteins in the blood to promote clotting. Spike proteins binding to the cells that line our blood vessels can cause these cells to over-produce cell-signaling cytokines that can potentially contribute to dangerous cytokine storms.
Various investigators have shown that the endocytosed spike glycoprotein, even in the absence of viral RNA, can induce a caspase-3 mediated cell death, complement activation, which could lead to a hypercoagulable state, and the increase of many cytokines/proteins associated with severe COVID-19, including TNFα, IL6, IL8, IL1β, and p38. Microclotting and vascular disease has been linked to neurodegenerative disease.
Additional studies related to microvascular injury and thrombosis:
Endothelial cell damage is the central part of COVID-19 and a mouse model induced by injection of the S1 subunit of the spike protein
Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: A report of five cases
ARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE 2
Inflammatory microclots in blood of individuals suffering from Long COVID
Prion spreading and exosomes
Exosomes provide an environment that can induce the conformational conversion of native proteins into aggregates that can be transmitted to otherwise aggregate-free cells in the brain.
Circulating exosomes are strongly involved in SARS-CoV-2 infection. But in this study, circulating exosomes with spike protein were noted after immunization. So, will these exosomes provide a transport system for neurological prion disease?
The role of prions has been shown in neurodegenerative diseases like Alzheimer’s, Parkinson’s disease, Huntington’s disease, amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). In this review the authors provided the latest information about the role of viruses, prions and miRNAs in neurodegeneration and neurodegenerative disorders leading to dementia. It is well known that amyloidogenic proteins or peptides, like Aβ, α-synuclein, tau, and huntingtin, can also spread from cell to cell or can be transmitted from animal to animal or human to animal in a prion-like fashion to cause neurodegenerative disease.
The last decade has shown progression in the establishment of circular miRNAs as a potential biomarker in the diagnosis of NDD.23 How will circulating mRNA post-vaccine potentially affect this balance? In this study the authors propose that we look beyond the established definition of what causes prions (infectious pathogens) to include the inducible transmissible entities undergoing autocatalytic conversion and consisting of RNA rather than protein.
The spike protein houses a prion domain; this was designed for higher affinity of the SARS-CoV-2 receptor binding domain (RBD) to the ACE 2 receptor.24
Credit: Dr. Richard Fleming
Viral persistence/viral reactivation.
Multiple different viruses can be reactivated after COVID and after the COVID vaccines including varicella, Epstein-Barr virus, hepatitis, herpes, herpes simplex, and cytomegalovirus.
Viral infections and inflammation subsequently may prime neurons and immune cells in the brain, rendering neuronal populations vulnerable to degeneration in the face of subsequent insults. The innate immune response is an early line of defense against microbes (bacteria or viruses) that is launched in the first hours of infection. Viruses can induce brain dysfunction by either direct cytolytic effects or bystander inflammatory reactions - and viral and microbial infections are a risk factor for NDD.25, 26
How the COVID vaccines work.
As noted in some settings, over the last few months there have been multiple studies and articles appearing in peer-reviewed and other scientific journals that discuss the potentially serious side effects occurring in some patients following vaccination.
The vaccine places a novel molecule (spike protein) in or on the surface of host cells. This spike protein is a potential receptor for another possibly novel infectious agent. That spike protein, encoded into every cell of the body and brain, can act as a beacon for future COVID 19 infections and therefore provide a rapid immune response.
All the injections induce genetic modification so that your body becomes a factory for spike protein production. Unfortunately, researchers have come to learn that the mRNA vaccines do not stay in the shoulder muscle. In fact, they have the potential to spread far and wide throughout the body via the blood. A recent report shows that the COVID spike protein gets into the blood where it circulates for several days post-vaccination and then accumulates in organs and tissues, including the spleen, bone marrow, the liver, adrenal glands and in “quite high concentrations” in the ovaries.
In a publication that reported on 13 young healthcare workers who received the Moderna vaccine. Researchers found detectable levels of SARS-CoV-2 protein in 11 of the 13 participants one day after first vaccination. “Spike protein was detectable in three of 13 participants an average of 15 days after the first injection… for one individual (Participant #8), spike was detected at day 29”, circulating in the blood. These findings are very concerning and require further urgent study.27
Where do we go from here?
I have reviewed various mechanisms that could trigger a tsunami of neurodegenerative disease, but have only scratched the surface of this complex topic and the potential implications for our brain health. I remained gravely concerned as to what the future may hold given the unprecedented increase in neurological problems that I have already seen in my own practice of 35 years, as well as in the studies we will continue to closely follow. While we do not as yet know what lies ahead, the need for ongoing and more in-depth research is clear. We are fortunate in that so many brilliant clinicians are continuing to provide additional insight regarding these ever-evolving events – so we remain hopeful that with more study, more investigations, and more clarity that we will have the answers we all need to best support our patients’ health. As always, please reach out to our offices if you have questions or would like to schedule a visit.
In hope and healing,
Dr. Suzanne Gazda
1 McGorray, M. MD. The neurological impact of COVID-19: What we know so far. Medical News Today. (February 3, 2022). https://www.medicalnewstoday.com/articles/the-neurological-impact-of-covid-19-what-we-know-so-far
2 Zhou, Y., Xu, J., Hou, Y. et al. Network medicine links SARS-CoV-2/COVID-19 infection to brain microvascular injury and neuroinflammation in dementia-like cognitive impairment. Alz Res Therapy 13, 110 (2021). https://doi.org/10.1186/s13195-021-00850-3
3 Oshiumi H (2021) Circulating Extracellular Vesicles Carry Immune Regulatory miRNAs and Regulate Vaccine Efficacy and Local Inflammatory Response After Vaccination. Front. Immunol. 12:685344. doi: 10.3389/fimmu.2021.685344
4 Becker JH, Lin JJ, Doernberg M, et al. Assessment of Cognitive Function in Patients After COVID-19 Infection. JAMA Netw Open. 2021;4(10):e2130645. doi:10.1001/jamanetworkopen.2021.30645
5 Søraas A, Bø R, Kalleberg KT, Støer NC, Ellingjord-Dale M, Landrø NI. Self-reported Memory Problems 8 Months After COVID-19 Infection. JAMA Netw Open. 2021;4(7):e2118717. doi:10.1001/jamanetworkopen.2021.18717
6 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; 1- 11. https://doi.org/10.1002/alz.12558
7 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
10 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
11 Raghavan S, Kenchappa DB and Leo MD (2021) SARS-CoV-2 Spike Protein Induces Degradation of Junctional Proteins That Maintain Endothelial Barrier Integrity. Front. Cardiovasc. Med. 8:687783. doi: 10.3389/fcvm.2021.687783
12 Arthur, J.M., Forrest, J.C. et al. Development of ACE2 autoantibodies after SARS-CoV-2 infection. PLOS One. (September 3, 2021). https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0257016
13 Chen R, Wang K, Yu J, Howard D, French L, Chen Z, Wen C and Xu Z (2021) The Spatial and Cell-Type Distribution of SARS-CoV-2 Receptor ACE2 in the Human and Mouse Brains. Front. Neurol. 11:573095. doi: 10.3389/fneur.2020.573095
14 Li, Z., Xu, X., Yang, M., Feng, J., Liu, C., & Yang, C. (2020). Role of angiotensin-converting enzyme 2 in neurodegenerative diseases during the COVID-19 pandemic. Aging, 12(23), 24453–24461. https://doi.org/10.18632/aging.103993
15 Idrees D, Kumar V. SARS-CoV-2 spike protein interactions with amyloidogenic proteins: Potential clues to neurodegeneration. Biochem Biophys Res Commun. 2021;554:94-98. doi:10.1016/j.bbrc.2021.03.100
16 Novellino F, Saccà V, Donato A, et al. Innate Immunity: A Common Denominator between Neurodegenerative and Neuropsychiatric Diseases. Int J Mol Sci. 2020;21(3):1115. Published 2020 Feb 7. doi:10.3390/ijms21031115
17 Liu, Y., Ebinger, J.E., Mostafa, R. et al. Paradoxical sex-specific patterns of autoantibody response to SARS-CoV-2 infection. J Transl Med 19, 524 (2021). https://doi.org/10.1186/s12967-021-03184-8
18 Aharya, Nimish & Nagele, Eric & Han, Min & Coretti, Nick & DeMarshall, Cassandra & Kosciuk, Mary & Boulos, Paul & Nagele, Robert. (2012). Neuronal PAD4 expression and protein citrullination: Possible role in production of autoantibodies associated with neurodegenerative disease. Journal of autoimmunity. 38. 369-80. 10.1016/j.jaut.2012.03.004
19 Rizk JG, Gupta A, Sardar P, et al. Clinical Characteristics and Pharmacological Management of COVID-19 Vaccine–Induced Immune Thrombotic Thrombocytopenia With Cerebral Venous Sinus Thrombosis: A Review. JAMA Cardiol. 2021;6(12):1451–1460. doi:10.1001/jamacardio.2021.344
20 Dionne A, Sperotto F, Chamberlain S, et al. Association of Myocarditis With BNT162b2 Messenger RNA COVID-19 Vaccine in a Case Series of Children. JAMA Cardiol. 2021;6(12):1446–1450. doi:10.1001/jamacardio.2021.3471
21 Heinz, F.X.; Stiasny, K. Distinguishing features of current COVID-19 vaccines: Knowns and unknowns of antigen presentation and modes of action. NPJ Vaccines 2021, 6, 104.
22 Eric, K.; Lea, K.; Jenny, R.; Silvia, B.; Stefan, K.; Rolf, M. “Vaccine-Induced Covid-19 Mimicry” Syndrome: Splice reactions within the SARS-CoV-2 Spike open reading frame result in Spike protein variants that may cause thromboembolic events in patients immunized with vector-based vaccines. Res. Sq. 2021
23 Dolinar, A., Koritnik, B., Glavač, D. et al. Circular RNAs as Potential Blood Biomarkers in Amyotrophic Lateral Sclerosis. Mol Neurobiol 56, 8052–8062 (2019). https://doi.org/10.1007/s12035-019-1627-x
24 Tetz G, Tetz V. Prion-like Domains in Spike Protein of SARS-CoV-2 Differ across Its Variants and Enable Changes in Affinity to ACE2. Microorganisms. 2022; 10(2):280. https://doi.org/10.3390/microorganisms10020280
25 Lotz SK, Blackhurst BM, Reagin KL and Funk KE (2021) Microbial Infections Are a Risk Factor for Neurodegenerative Diseases. Front. Cell. Neurosci. 15:691136. doi: 10.3389/fncel.2021.691136
26 Lensen R, Netea MG, Rosendaal FR. Hepatitis C Virus Reactivation Following COVID-19 Vaccination – A Case Report. Int Med Case Rep J. 2021;14:573-576
27 Alana F Ogata, Chi-An Cheng, Michaël Desjardins, Yasmeen Senussi, Amy C Sherman, Megan Powell, Lewis Novack, Salena Von, Xiaofang Li, Lindsey R Baden, David R Walt, Circulating Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine Antigen Detected in the Plasma of mRNA-1273 Vaccine Recipients, Clinical Infectious Diseases, Volume 74, Issue 4, 15 February 2022, Pages 715–718, https://doi.org/10.1093/cid/ciab465
Additional related reading:
SARS-COV-2 VACCINES AND NEURODEGENERATIVE DISEASE
Innate Immune Suppression by SARS-CoV-2 mRNA Vaccinations. The Role of G-quadruplexes, Exosomes and MicroRNAs"
Worse Than the Disease? Reviewing Some Possible Unintended Consequences of the mRNA Vaccines Against COVID-19
COVID-19 RNA Based Vaccines and the Risk of Prion Disease