A few weeks ago, I diaried in depth about Covid, as has been my wont over the past year. However, in this last diary, not only did I advance what may be rather cutting-edge understandings about Covid’s methods of interaction—that it can directly invade through the nose, that it can inflict Alzheimer’s-like damage—I went out on a limb and speculated even further, saying that it may even be possible that Covid could induce something resembling a prion disease.
The diary received some pushback in the comments, which while expected was a bit surprising in some of the particulars. I realize that was somewhat exposing myself to criticism along an axis that could be considered getting ahead of the science, a proverbial cart before the horse (though I was using logic to advance these ideas). So I resolved to dive a little deeper and maybe resurface with something more faceted and compelling.
This is lengthy, but there is a tl;dr at the end. (Please bear with me! The endnote references are alphabetized, so be sure to align in-line references with the correct numeral.)
That Covid causes neurological symptoms has been well established. In addition to being characterized as being “at the same magnitude as intoxication at the UK drink driving limit or 10 years of cognitive ageing”8, just this week (January 26, 2023), George Monbiot at the Guardian14 provided further perspective:
The impacts of long Covid, according to health metrics researchers, are “as severe as the long-term effects of traumatic brain injury”. Now that we know how the virus attacks our cells, “traumatic brain injury” looks less like an analogy than a description.
Severe concussive damage is a direct parallel to what is going on in the brains of some Covid sufferers.
Not to be a downer! Many of us have contracted Covid and would not like to think of the ramifications of the disease as being so dire. But consider that approximately 20 million Americans are estimated to suffer from some form of Long Covid,19 and that about 30% of those people list cognitive, psychiatric or other neurological problems as their primary complaint.7 (At the same time, it’s acknowledged that only a third of COVID-19 infections are symptomatic5, so there are probably vast numbers of silent sufferers of Covid, some of whom may not even themselves know that Covid could be a culprit.)
One major influence of Covid on cognitive function to which scientists have pointed has been that of inflammation. Brought on in many cases by immune molecules known as cytokines (the cascade of which is “cytokine storm”),26,27 this inflammation can bring about among other things tissue swelling (edema), which in the brain can distort the actual shape of neurons.
Blood flow can be restricted or dammed altogether (especially if other processes have caused microclots to form, another Covid hallmark).
If the immune system gets caught in this feedforward process, resident macrophages known as microglia can activate and begin trying to clean up debris, but in so doing the microglia may mistake one’s own body as a foreign substance. It can begin munching on dendrites of neurons—that is, the little hair-like appendages that allow the neurons to receive messages.2 (I’ve written about microglia in the context of Covid here.) I’ll return to microglia a little later.
Another thing that can happen within this cytokine cascade is that the immune system can begin producing excessive amounts of something known as kynurenic acid,10 sometimes in an effort to bring neuroinflammation under control. However, the same general pathway that causes this material to be made also can lead to its neurochemical opposite, quinolinic acid, which is neurotoxic. The brain is a murky soup at this point, which opposing processes fighting it out in a very delicate arena.
Because kynurenic acid attempts to rescue the brain by tamping down activity at what’s known as NMDA receptors,10 a particular receptor in the brain for excitatory neurotransmitters, it ultimately acts to send the brain into a state of hypofunction. The NMDA receptors react on a somewhat lengthy timeframe, as neuronal impulses (known as action potentials) are sustained over longer periods of time than AMPA receptors, which operate at very brief increments of time. In fact, the two often modulate an overall neural signal, so both are important to neural transmission. (I touched on some of these interactions in my previous Covid diary.)
If the NMDA receptors are suffering from what’s known as NMDA blockade, this means that those receptors will be working at less than efficient capacity. The manner in which this manifests depends on the area of the brain where the cascade is happening. In acute and long Covid, this has been demonstrated to happen in the frontal areas especially (though other areas may see this happen, too).
Frontal hypofrontality could be an overall dimming of power, a distortion in where enough signal can boost so as to properly propagate (this could even lead to otherwise distinct and reciprocal neural networks becoming merged or functionally fused), or possibly wetware destruction, where the receptors are physically deformed due to extracellular conditions (pH, pyrexia, pinballing macrophages) or demolished altogether due to cellular apoptosis (that is, self-directed elimination, itself possibly caused by certain immune factors).6
What does frontal hypofrontality look like to an observer? Well, a person might look drunk. If NMDA receptors are blocked, the main excitatory neurotransmitter—glutamate—cannot effectively enter certain cells, such as those that help coordinate movements. In fact, NMDA and dopamine, a chemical used by the brain to spur motility, often fire together; so if one is missing from a necessary constellation of signals from one neuron to the next, the entire message might be garbled. Thus uncoordinated movement might be a sign.
Also, a person might observe signs that look like disinhibition and impulsivity. The erstwhile patient might be undergoing what for all purposes looks like a personality change. They may be overactive and hyper, edging maybe even into mania; they may, conversely, retreat into mutism and rigidity, or lapse into dissociation. They may be irritable, more emotional, perhaps even less in control of their temper. They may be overly familiar with people in what would be a new turn of physical appreciation—petting or other advances—that most other folks would recognize as not being appropriate for the given circumstances.
This general constellation of symptoms, of which not all need be present, looks and acts like frontotemporal dementia. In this dementia, memory loss does not prominently figure. More loss of control, more heightened emotionality, and lack of caring typify the condition, a lack of regard.
The main area of the brain affected in this case is known as the orbitofrontal cortex, which I wrote about here. Other areas may also play roles (such as other frontal structures like the dorsomedial prefrontal cortex, and an area known as the basal ganglia,5 a gray matter structure that is below the surface of the brain that serves as a juncture between the newer and more ancient parts of the brain), creating a picture of someone who behaves in a way contrary to their normal behavior.
These issues of neurochemicals out of balance and areas of the brain underperforming or disabled due to SARS-CoV-2 infection, these have been known for some time, though it appears that last year a good deal more became clarified in the publicly accessible scientific press. Several watershed studies, particularly the UK BioBank study, really advanced our understanding of how the virus affects the brain (for example, scientists out of UC Davis in a primate study3 demonstrated with a high degree of confidence that SARS-CoV-2 can directly invade the brain through the nostrils). This fuller picture finally lets us peer through a window that otherwise would be more akin to a black box.
What’s going on under the hood?
We’re still getting a better idea of all of the possible mechanisms and pathways that may be altered or disturbed in Covid, but Esposito and colleagues9 showed that the olfactory system can undergo physical remodeling.
[M]ore supra-threshold functional connections occur for the group of COV+ subjects, linking the APC node, not only to the closest sensory nodes along the posterior piriform cortex-APC-OFC axis, but also to additional limbic nodes within primary olfactory areas (olfactory tubercle, amygdala) and to posterior-middle OFC, which, in turn, also appear more inter-connected among themselves.
Beyond APC, extra connections can also be noted for the group of COV+ subjects between the (sensory) PPC node and additional limbic nodes (e.g., entorhinal), while it appears there is a lack of functional connectivity in the COV+ group between at least two sensory nodes in the insula (posterior and ventral insula) and two limbic nodes in the hippocampus (anterior and posterior hippocampus).
A post hoc comparison of the mean functional connectivity (two sample t-test with signed values) on inter-module connections between COV+ and COV groups, resulted in a significantly (p <.05) increased functional connectivity between PCC and entorhinal and a reduced functional connectivity in three connections between insula and hippocampus nodes.
(APC is the anterior piriform cortex, which fits in snugly with the entorhinal cortex, olfactory areas, amygdala and hippocampus. See figure. Also: PCC = posterior cingulate cortex, another area of the limbic system which helps direct decision-making and social cognition. OFC=orbitofrontal cortex. The insula is a subsurface gray matter structure.)
In other words, neural networks that normally would send separate signals to cognitive areas (frontal lobe and/or the thalamus, the brain’s central processing center) begin to become physically fused, firing together in ways that normally they would not. Additionally, other areas that should be connected lose contact. The olfactory system as well as parts of the limbic system (famously containing the amygdala, known as the brain’s alarm bell) can join to send unusual or confused messages.
These changes may be permanent; we simply do not know at this time.
But that’s not the only type of physiological remodeling that may be going on. In addition to the microglia overly ambitiously eating precious dendrites from the neural processes, they might even attack fellow support cells known as oligodendrocytes. (I’ve written about oligodendrocytes here.) These are cells that support neurons by ensheathing them in insulating myelin, a material that boosts neurons’ electrical signals. If microglia degrade these myelin sheaths, the conductance velocity of those neurons could slow by about three orders of magnitude.
Watch microglia at work addressing a perforation in tissue.
Profound changes are occurring in the brain. But is that all?
In my last Covid diary, I advanced the idea—which I acknowledged was somewhat early, more of a projection from variables I was taking into account rather informally—that Covid might represent something that functions like a prion disease. I made the statement, as I noted, after sitting on the speculation for quite some time (over a year). I came forward with it because I felt, and still feel, that the level of neurodegeneration experienced by certain individuals, the degree and the swiftness of the deterioration, indicates that perhaps if an Alzheimer’s-like process21 was going on, it could indeed be on a faster time table.
Almost all of our known human neurodegenerative diseases are relatively long-lasting, except for ALS (aka Lou Gehrig’s disease, which is a motor neuron disease), and a handful of others. Conversely, prion diseases are known to advance with swift onset.
Not only has Covid been shown in some cases to descend with rapidity, causing confusion, delirium, and other signs of possible organic deterioration (hallucinations can arise as sequela from temporal lobe epilepsy, a possible complication of Covid infection),9 varied individuals have shown extraordinary changes at autopsy, including gliosis,7 which can lead to pockets where brain tissue is occupied by glial cells instead of gray or white matter.
What does that have to do with prion disease? Well, when I considered how the hippocampus might find itself remolded in Covid as mentioned above, I saw a similarity between that and Alzheimer’s in their patterns of plaque deposition. So, this might be the fastest-moving Alzheimer’s the world has yet encountered; or possibly this virus has acquired properties that other viruses haven’t.
An intrepid reader in my last diary pointed me helpfully in the direction of a paper by Hara and colleagues11 that demonstrated in several ways that a strain of the Influenza A virus (the same as related to the 1918 flu pandemic) can induce both protein misfolding and protein aggregation in human cells. (These were results in vitro.) While the cells were neuroblastoma cells—cancer—at least one other team described the findings as proof that such a mechanism was possible as a viral legacy. The aggregates are known as seeds and serve as templates for more prion protein, known as PrPC, to misfold and join the group.
The rogue prion protein, PrPSc, is called that as it gives rise to what’s known as scrapie in sheep. Prion diseases affect both humans and nonhuman animals, a notorious example of which came to be known as mad cow disease. In the ‘90s, Britain suffered a tragic food contamination catastrophe, where infected cattle, who’d themselves been fed infected beef trimmings that included brain material, were slaughtered and sold on the open market. This disease in cattle is called bovine spongiform encephalitis, and the human form obtained through the diet is known as Creutzfeldt-Jakob disease. (The scandal was eventually addressed, though in a less-than-timely manner; and those people affected have all since passed; there’s no current emergency on this front.)
Spongiform means that the brain becomes sponge-like, in that it develops large vacuoles—empty spaces—where before there had been tissue. This disease happens in the context of encephalopathy, which is an overall swelling of the brain, sometimes leading to increased cranial pressure that can in itself be a risk factor). These diseases generally strike within a year, wherein the patient suffers sensory derangement, fatigue, ataxia (unsteady gait), myoclonus (brief, uncontrolled muscle jerks), memory loss, and even EEG abnormalities. Eventually, the body cannot withstand the onslaught of deterioration.
In the previous diary I was challenged for submitting this idea to scrutiny, perhaps due to it being offered at a juncture that may have seemed premature. Indeed, I got the sense (though I may be mistaken) that this idea seemed to at least one reader to be so far-fetched as to be rejected out-of-hand. So, using the Hara paper as a springboard, I looked into more information along the prion-virus front.
I felt so bold as to directly search for “SARS-CoV-2” and “prion”. My efforts returned several papers on that hybrid topic,1,4,20,27 including some that dealt with Covid as a neurodegenerative disease that could self-assemble prion-like seeds or aggregate them.6,12,22 For example, Zhao and associates27 stated directly that
Bernardini et al. (2022) recently described a ∼40 year old male COVID-19 patient who developed CJD 2 months after COVID-19 onset with presenting symptoms of visuospatial deficits, hallucinations, ataxia and diffuse myoclonus—and their study concluded that the short interval between SARS-CoV-2 respiratory and CJD neurological symptoms was indicative of a causal relationship between a COVID-mediated neuroinflammatory state, protein misfolding and subsequent aggregation of PrPc into PrPSc, and emphasized the role of SARS-CoV-2 as an significant viral initiator of neurodegeneration[.]
(emphasis added)
Similarly, Tavassoly and colleagues22 advanced:
Like other viruses, one of the possible outcomes of COVID-19 might be pathology development in the brain that might serve as an environmental factor to accelerate neurodegeneration due to an increase in the brain protein aggregation.
This paper addressed two possible mechanisms through which this virus can increase aggregation of brain proteins: (1) seeding protein aggregation on intact viral particles by spike proteins and (2) a peptide derived from spike protein acting as functional amyloid to cross-seed aggregation of brain proteins. In both of these mechanisms, the role of SARS-CoV-2 is to serve as a seed to catalyze and accelerate the aggregation of brain aggregation proteins.
(emphasis and paragraphing added)
Why would this be so? Some scientists have found features in the spike protein of SARS-CoV-2 that sets it apart. According to Zhao et al.,27 “[S]everal recent reports link multiple aspects of the ‘S1’ spike protein structure and function, immunology and epidemiology with PrD, prion-like spread and prion neurobiology” (p. 3). Corroborating that, Shahzad and Willcox20 found that
PrDs [prion-like domains] have been identified in the spike proteins of SARS-CoV-2[.] The spike protein binds to receptors on human cells. Although SARS-CoV and SARS-CoV-2 both bind to angiotensin-converting enzyme-2 (ACE2), SARS-CoV-2 binds at 10 to 20 times higher affinity[.] SARS-CoV-2 has been reported to be the only coronavirus with such a unique distribution of PrDs in its spike protein, which occur at the receptor-binding domain at S1 region.
(emphasis added)
So in this regard, the S1 protein is special.
What else about the spike protein? Well, in addition to its efficient method of cell entry, it has been shown to stimulate amyloid production. Baazaoui and associates1 offered this into the record:
The cleavage of the SARS-COV-2 virus via its spike protein at the S1/S2 site and the S2’ results in a cleavage of a peptide (∼150 Aas [amino acids]) the pathological function of which is still unknown. If this peptide is dissociated and released into the intracellular or the extracellular space it might induce some immunological reactions or act by itself as a functional amyloid. Hence, this peptide could seed aggregation of brain proteins as a possible pathological mechanism like some viral and bacterial-derived functional amyloids.
Additionally, Bernardini and colleagues4 said, “It has been recently demonstrated that SARS-CoV-2 spike proteins show high affinity for amyloid-forming proteins, the highest being for PrP” (p. 81, emphasis added).
Amyloid, a substance that is implicated in a wide variety of neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and Pick’s disease (a form of frontotemporal dementia) among others, can accumulate in the brain without being broken down by the brain’s normal processes. These insoluble particles can interfere with neuronal conduction of messages, which can be devastating. The hippocampus, for example, a key center for memory, visuospatial orientation and situational context, is especially susceptible to this process in the unfolding of Alzheimer’s disease, in the form of amyloid-beta (Aβ) deposition. This can cause acute and intractable damage to these sensitive tracts.
Not only might SARS-CoV-2 induce the brain’s own resident prion protein (PrP, normal physiologically) to undergo this rapid dilapidation, it could leave its own template behind in the form of the cleft segment of ~150 amino acids.12 This protein’s function is otherwise unknown; but it could be the genesis of an amyloid criticality. Charnley et al.6 found that this may be due to the viral replication cycle. Showing that a particular open reading frame (ORF, a mechanism involved in gene transcription; in this case, ORF6) produced a fragment termed I14LLIIMR (aka ILLIIM), the team noted,
The significant increase in apoptosis and reduction in cell number seen for ILLIIM [the cytotoxic protein] correlates with the work of Lee et al. who have previously shown that the ORF6 protein (that contains the ILLIIM sequence) is the most cytotoxic protein in the proteome of SARS-CoV-2[.] Combined with our data, this suggests that this toxicity might be due to the amyloidogenic nature of this short protein.
The fragment also is replete with β-pleated sheets,6 a conformational shape indicative of pathological prion protein.
This is important because, as infectious disease expert Jing Zhang explained, neurotropic viruses and prions share many aspects in common.26
Since pathological proteins such as beta-amyloid, tau, alpha-synuclein and transactive response DNA binding protein 43 (TDP-43) in AD [Alzheimer’s disease], PD [Parkinson’s disease] or ALS act like prions in misfolding, aggregating, seeding, and spreading in the brain, these neurodegenerative disorders have been called prion-like diseases[.] In addition, prion diseases (such as Kuru and Creutzfeldt-Jakob disease) are both infectious diseases and neurodegenerative disorders. Thus, prion diseases and prions are the links between infectious diseases and neurodegenerative disorders.
Both prions and such viruses are infectious agents that can wreak tremendous organic damage. The one major difference, the expert stressed, is that viruses are contagious—propagated by incidental contact, while prions are not easily transmitted (the range restricted to direct contact with bodily fluids). Should a prion disease acquire traits seen in viruses, however, in terms of transmissibility that would fundamentally change the dynamics, as in such an instance prions would become the greater threat. Alternatively, SARS-CoV-2 might be a virus that has picked up prion-like traits that could kickstart this rogue process and, in fact, the spike protein provides a basis for considering this.
A last point generally, in this brief overview of how SARS-CoV-2 possesses prion-like behaviors, one should look at the brain regions of interest, or ROIs, in a side-by-side comparison.
It turns out these two diseases have significant overlap. I mean not to present an exhaustive list, but of the sources I have been able to collate so far, sporadic Creutzfeldt-Jakob disease (sCJD) has been known to affect portions of the brain involved in various levels of cognition. (‘Sporadic’ means there is no known etiology, or origin, of the disease; it may have arisen in an individual spontaneously.)
Notably, the olfactory centers are specially remodeled in sCJD.
In contrast to the results obtained in postmortem samples, we observed a marked deposition of PrPSc in ciliated dendrites of olfactory sensory neurons and in a proportion of basal cells (Fig. 2A and B). This is at variance with the negative PrP staining in olfactory biopsy specimens obtained from subjects without neurologic disorders and from patients with AD.25
Immunostaining for PrP was negative in the olfactory epithelium of all postmortem and biopsy specimens from controls (Fig. 2A). In contrast, immunohistochemical analysis revealed marked deposition of PrP in the cilia of olfactory receptor neurons and a faint PrP immunoreactivity in basal cells of the olfactory epithelium from all patients with sporadic Creutzfeldt–Jakob disease (Fig. 2B and 2C). Conversely, the respiratory epithelium did not stain for PrP (data not shown). In the brains of patients with sporadic Creutzfeldt–Jakob disease, there was selective deposition of PrP in olfactory bulb glomeruli (Fig. 2D), olfactory tracts (Fig. 2E), and primary olfactory cortexes (Fig. 2F).24
(emphases added; panels referenced found in figure just above)
Reuber and colleagues16 said of variant CJD (the human form of bovine spongiform disease):
Spongiform change and plaques were most prominent in the cortical regions and cerebellum. Plaques were particularly dense in the molecular and granular layers of the cerebellar cortex. Neuronal loss, gliosis, and spongiform change were most conspicuous in the basal ganglia and thalami. Immunohistochemistry for prion protein … showed prominent staining in the plaques and diffusely in the neuropil of cerebral and cerebellar cortices. The olfactory tract showed prominent and diffuse staining for prion protein (PrP) associated with vacuolation[.]
There were significant histopathological changes [that is, revealed by certain staining techniques] in the basal forebrain where both taste and smell are represented[.]
The authors summarize: “[T]he diagnosis of vCJD [variant Creutzfeldt-Jakob disease] should be considered if hypogeusia and hyposmia are accompanied by changes of personality and other, more ‘typical’ features of vCJD.”16 The effects of loss of smell and/or taste—anosmia and ageusia, respectively—were a defining hallmark of Covid when the disease first descended; and they remain reliably reported complaints.
Regarding sporadic CJD, the diagnostic criteria implemented in Zanusso et al.’s research (2003, p. 712) included:
- progressive dementia over a two-year period;
- myoclonus;
- visual or cerebellar symptoms (or both);
- pyramidal symptoms or extrapyramidal symptoms (or both) [often reminiscent of tardive dyskinesia];
- akinetic mutism;
- EEG signatures showing complexes of periodic sharp and slow waves
EEG, which stands for electroencephalogram, is a measure of brainwave activity. Periodic sharp and slow waves, besides being a signature for prion disease, is also seen in certain sleep disorders, as well as a handful of non-neurological disorders. In the case of periodic sharp and slow waves, these feature delta waves, known to occur in the deepest sleep.
As it happens, Covid has been associated with “epileptiform abnormalities on EEG” per Lin et al.13 (see also Nuzzo et al.15; Sanchez et al.17). Other researchers have found associated with COVID such patterns as diffuse, rhythmic or continuous periodic oscillations, in the lowest registers of activity.
In fact, Vellieux et al.23 stated that in the first Covid EEG case studies of their kind, patients had “continuous, slightly asymmetric, monomorphic, diphasic delta slow waves.” Moreover, Schiff and Brown,18 speaking in their roles as anaesthesiologists who manage brainwave activity as their profession, stated, “While EEG findings in COVID-19 are only just emerging, many COVID-19 patients show severe slowing and discontinuous, intermittent EEG patterns similar to burst suppression.” Other studies have noted similar abnormalities.
Beyond EEG disturbances, the other symptoms listed above in vCJD are seen frequently in COVID. (I am unaware of any firmly documented cases of COVID dementia stretching into the two-year mark, I must admit. At the same time, if they are being classified as Alzheimer’s or other dementias, it would be difficult to get a proper grasp on the scope of the situation.)
More symptoms specific to Covid are the following26:
[M]icrovascular injury was observed in the olfactory bulb, brain stem and basal ganglia (including substantia nigra) in COVID-19 patients[.] In addition, the presence of SARS-CoV-2 was detected in the CSF [cerebrospinal fluid] of 6% patients who had acute neurological symptoms[,] in the brains (frontal lobe, basal ganglia, brain stem, cerebellum, etc.) of 21 (53%) deceased patients[,] and in the substantia nigra of 6 patients[.]
(emphases added)
This compares to a description of vCJD given by Reuber and associates16:
Postmortem neuropathological and histological examination confirmed the diagnosis of vCJD. In addition, there was evidence of bronchopneumonia. Sections of brain (brain weight 1322 g) showed extensive tissue involvement with prominent neuronal loss, astrocytosis, spongiform change, and numerous Kuru-type plaques, including florid plaques. These changes were seen in the cortices of frontal, parietal, temporal, and occipital lobes, basal ganglia, thalami, periventricular grey matter, brain stem, olfactory areas of the cerebrum, and the cerebellar cortex.”
(emphasis added)
Caveats, Detection, and Possible Future Paths
A few things to wrap this diary (though the topic is not nearly complete or exhausted):
I do not mean to imply that all people who have had or who will catch Covid will experience these neurological changes. Everyone has their own genetic heritage, which may confer protection, susceptibility, or a neutrality with regards to this type of neurodegeneration. Also, individual habits of social behavior, up to and including cooperating with community efforts to reduce Covid spread, will be a further determining factor. At least one study has shown distinct differences in demographic cohorts in terms of their willingness to incorporate these behaviors; and some of these same people prove to be similarly subject to reinfection.
How would we determine if this type of thing truly is happening? I think we can attempt to do this on the front end by designing longitudinal cohort studies, especially those that would compare Covid neurodegeneration with that of sCJD, for example.
Another proactive thing to do would be to run real-time tests for the PrPSc protein. As we learned above, testing for the prion protein does not overlap or coincide with markers that would normally show up in non-prion brain disease. There now exists a test called RT-QuiC that can determine with reliable sensitivity if the PrPSc protein is present in a patient. (Still, any definitive test would come at autopsy.) Perhaps those diagnosed with Covid cognitive problems could be offered this test if they also showed other signs of more advanced or rapid degeneration, especially as corroborated by EEG or other imaging such as MRI (magnetic resonance imaging). However, right now, we’re not testing for this at all. We need data capture to adequately get an idea of the problem’s scope: if we never look for it, we won’t detect it.
On the back end, we have sociological methods. We measure after the fact. So, in a general population, there will be standard rates of disease for each of the maladies discussed herein (the various dementias like Alzheimer’s, corticobasal dementia, frontotemporal dementia, etc.; but also ALS, Huntington’s chorea [which itself has prion-like aspects], and so on). In due time, if the theory bears out, statistically significant increases should make themselves apparent soon in observational data.
Still, Serrano et al.19 estimated (with my emphasis), “If the 20% rate of [SARS-CoV-2] brain invasion we have documented here is a valid estimate for all those that have been infected, then with 20 million US COVID-19 cases there could be 4 million with the potential for long-term viral CNS persistence.” Part of that picture could be a prion-like aspect (or contingency) of Covid.
At the same time, I also want to caution against pigeonholing or scapegoating anyone. Unfortunately but apparently, Democrats might be more likely than political counterparts to stigmatize a person for getting Covid. This is something to keep in forefront of mind, because it is not a moral failing to have contracted Covid. In fact, it’s estimated that the vast majority of people have or statistically speaking are due to get Covid. And once you get it, it’s rather a crapshoot as to what symptoms may manifest, and whether or not they will be long-term.
I think about this because, in a completely different context, I recently came across a video about the families of those individuals who were failed by the health system of their country (in this case, Australia), where the person and their loved ones had tried to get them help through mental services, but the help came only after the person had committed some horrendous crime (proof enough, perhaps, that maybe they do need state attention). The families are anguished about the fact that they attempted to do all they could to get assistance; and in the video their heartbreak comes through. As someone trained in sociology, I would like to stay mindful of this type of scapegoating, a reflexive behavior.
But I wanted to post this and follow up my previous Covid diary because I plan to return to this idea. It was only fair for me to expand on the points that came up in the comment section of the previous diary. Certainly it’s incumbent upon me to make these notes available, if anyone would like to be able to trace my own source materials to see how I substantiated this idea. References will be below, and I plan to import them in a separate post so that they’re also standalone.
If you’ve read this far, thank you for sticking with me. In sum, what I’ve presented here is that the S1 spike protein of SARS-CoV-2 has prion-like characteristics that may indeed induce prion-like activity, in terms of seeding protein self-aggregating templates for regular prion protein to copy into a malformed shape. If this is occurring, especially with the other deleterious activities going on in a COVID-affected brain at any one time (i.e., neuroinflammation, etc.), it’s possible that the patient would be in a race against time to preserve his or her brain from one of the worst of possibilities, spongiform disease.
But if nothing else, I hope I have left with you a clear look at how Covid indeed is a brain illness.
Covid & PrP – Works Cited & References for Further Reading
- Baazaoui, Narjes and Khalid Iqbal, “COVID-19 and Neurodegenerative Diseases: Prion-Like Spread and Long-Term Consequences.” Journal of Alzheimer’s Disease (2022), Vol. 88, No. 2. doi: 10.3233/JAD-220105
- Baranova, Ancha et al., “Severe COVID-19 increases the risk of schizophrenia.” Psychiatry Research (2022), Vol. 317, Article 114809. doi: 10.1016/j.psychres.2022.114809
- Beckman, Danielle et al., “SARS-CoV-2 infects neurons and induces neuroinflammation in a non-human primate model of COVID-19.” Cell Reports (2022), Vol. 41, Article 111573. doi: 10.1016/j.celrep.2022.111573
- Bernardini, Andrea et al., “Creutzfeldt-Jakob disease after COVID-19: infection-induced prion protein misfolding? A case report.” PRION (2022), Vol. 16, No. 1. doi: 10.1080/19336896.2022.2095185
- Bhinder, Khurram et al., “Bilateral basal ganglia ischemia associated with COVID-19: a case report and review of the literature.” Journal of Medical Case Reports (2021), Vol. 15, Article 563, p.1. doi: 10.1186/s13256-021-03165-x
- Charnley, Mirren et al., “Neurotoxic amyloidogenic peptides in the proteome of SARS-COV2: potential implications for neurological symptoms in COVID-19.” Nature Communications (2022), Vol. 13. doi: 10.1038/s41467-022-30932-1
- Crunfli, Fernanda et al., “Morphological, cellular, and molecular basis of brain infection in COVID-19 patients.” PNAS (2022), Vol. 119, No. 35. doi: 10.1073/pnas.2200960119
- Davis, Hannah, Eric Topol et al., “Long COVID: major findings, mechanisms and recommendations.” Nature Reviews Microbiology (2023), p. 4. doi: 10.1038/s41579-022-00846-2
- Esposito, Fabrizio et al., “Olfactory loss and brain connectivity after COVID-19.” Human Brain Mapping (2022), Vol. 43, No. 5. doi: 10.1002/hbm.25741
- Fesharaki-Zadeh, Arman et al., “Clinical experience with the 𝛂2A-adrenoreceptor agonist, guanfacine, and N-acetylcysteine for the treatment of cognitive defects in Long COVID-19.” Neuroimmunology Reports (2023). doi: 10.1016/j.nerep.2022.100154
- Hara, Hideyuki et al., “Neurotropic influenza A virus infection causes prion protein misfolding into infectious prions in neuroblastoma cells.” Nature Scientific Reports (2021), Vol. 11, Article 10109. doi: 10.1038/s41598-021-89586-6
- Idrees, Danish and Vijay Kumar, “SARS-CoV-2 spike protein interactions with amyloidogenic proteins: Potential clues to neurodegeneration.” Biochemical and Biophysical Research Communications (2021), Vol. 554. doi: 10.1016/j.bbrc.2021.03.100
- Lin, Lu et al., “Electroencephalographic Abnormalities are Common in COVID-19 and are Associated with Outcomes.” Annals of Neurology (2021), Vol. 89, No. 5. doi: 10.1002/ana.26060
- Monbiot, George. “We are all playing Covid roulette. Without clean air, the next infection could permanently disable you.” The Guardian, January 26, 2023. http://www.guardian.com/commentisfree/jan/26/covid-roulette-clean-air-ventilation-long-covid
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