I’ve been working toward a Covid diary more in-depth than this, but there were some developments that have come to public attention in the last month or so, and I felt remiss if I passed up the opportunity to let people know of these updates. Many people have already left for Thanksgiving travels, but perhaps this will encourage people to mask when the situation calls for it.
I say mask because we’ve recently gotten further confirmation that Covid can be transmitted directly through the nose. (There was a slight caveat to that study, but when combined with others it seems that the indicators are indeed that nasal invasion is a pathway.) So please, if you’re around people outside of your regular household, think about barrier protection. Even if you’ve been vaccinated, masking can offer added protection against this avenue of infection.
I also may have passed up writing this diary were it not for a conversation I had with my best friend five days ago. I told her of this first item, that Covid has been associated with Alzheimer’s-like symptoms, and she took it in stride, as though she already knew what I was talking about. Then she brought up her previous bout with Covid and how she had “brain fog” (something she’d described as “the worst headache of my life”), and that thankfully it had gone away.
It wasn’t until we’d ended our phone call that I realized that she’d fundamentally misunderstood me. Brain fog from Covid can indeed resolve. But Alzheimer’s-like symptoms means neurodegeneration, and that generally does not resolve so simply.
COVID-19 causes Alzheimer’s-like symptoms
The full name of the study is SARS-CoV-2 invades cognitive centers of the brain and induces Alzheimer’s-like neuropathology.
The paper was pre-published September 6, 2022 on bioRxiv, so it has not been peer-reviewed. However, the study was an autopsy sample, and their methodology is sound, using tissue from recognized tissue banks. “The 17 COVID-19 cases were matched to 17 non-COVID-19 cases by age, underlying diseases, postmortem intervals, retrieval time window, and other parameters when it is possible,” the authors wrote. Seventeen cases may seem like not a lot, but that is more than sufficient for the type of study conducted.
The researchers, working together from both University of Maryland School of Medicine and University of California San Diego
detected SARS-CoV-2 RNA in all 17 COVID-19 cases but not in the 17 matched non-COVID-19 cases, in the three cortical regions, the entorhinal (ENT) cortex, the inferior frontal cortex (IPC) and the dorsolateral prefrontal cortex (DPC).
(My emphasis.)
To start off, here is a related brain atlas, to bring a clearer window.
Inferior frontal gyrus: middlemost-labeled structure on the left (that is, fourth down)
That’s “cut” on the sagittal plane through the midline of the brain (or just before), presented as though viewing the left hemisphere after cutting away. The inferior frontal gyrus is near the general center of the brain. It performs several functions, foremost of which is that of expressing speech: it houses what’s known as Broca’s area. Damage to Broca’s can cause expressive aphasia, a condition where language is understood by the patient but he or she cannot communicate intelligibly with others.
Dorsolateral PFC is the topmost structure.
The dorsolateral prefrontal cortex is part of the overall prefrontal cortex, which means it helps with executive function, such as working memory and selective attention. According to Wikipedia, it “is also the highest cortical area that is involved in motor planning, organization and regulation.” Additionally, it helps guide our social behaviors. It helps interpret speech and furthermore is directly connected with structures associated with the limbic system. The limbic system is renown as the seat of emotional regulation.
If you’ve two minutes, you can learn more about the prefrontal cortex here:
The entorhinal cortex (which I’ll abbreviate EC) is a waystation between the olfaction region (known as the piriform cortex) and the temporal lobe, which houses memory. Specifically, it lies between the olfactory bulb to the hippocampus, relaying information about odor and activating the areas that bring into memory information associated with that odor. The EC coordinates several systems and it too connects directly with the limbic system.
This leads directly into a separate paper, published by Cell Reports November 1, 2022, by a team out of UC Davis, titled SARS-CoV-2 infects neurons and induces neuroinflammation in a non-human primate model of COVID-19. It had been prepublished not too long ago, and I highlighted the press release then when the team spoke publicly of their findings. However, I had not gone into the paper in-depth, and I now mean to in a future diary. For this diary, though, I wanted to bring forward one of their simplified cartoons, to give a better idea of the affected areas.
OB: Olfactory bulb. OT: Olfactory tubercle. PC: Piriform cortex. OFC: Orbitofrontal cortex. EC: Entorhinal cortex.
So you see how these structures connect.
Another map I wanted to show comes from this reference: Functional connectome analyses reveal the human olfactory network organization (2020). It’s one thing to see a cartoon schematic such as the one above; but a bird’s-eye view might give a helpful second viewpoint.
Entorhinal cortex is #4, which is on the furthest right, near the inside center of the hemisphere (axial view), in red. It’s a bit hard to read at this resolution; the original paper has a fantastic image on p. 29.
That gives you a rough idea. Putting these findings together, one can see that if Covid enters the nose and travels into the body through that direct route, it has a clear shot at directly disturbing the centers of olfaction, which lead to these other highly important structures that deal with memory, coordination, social behaviors, perception and assessing risk, organizing and expressing speech, and many other functions.
What did the group from Maryland and UC San Diego find about these areas, with regards to Covid? That “viral RNA has been detected in 36.4% of brain biopsies of fatal COVID-19 cases”. The researchers acknowledge that this “suggest[s] that SARS-CoV-2 invades some COVID-19 patients’ brains but may not invade all patients’ brains.”
Although it is still controversial whether SARS-CoV-2 invades patients’ brains, we provide strong evidence that SARS-CoV-2 can invade the cognitive centers of the brain, leading to AD-like neurophenotypes in both non-neurodegenerative disease and neurodegenerative disease individuals.
They spell it out:
COVID-19 patients and survivors experience AD-like neural syndrome including memory loss, delirium and cognitive deficits, suggesting that there is a cellular mechanism underlying these phenomena.
(My emphasis.) This adds to the growing body of work that locates neurodegenerative biomarkers such as amyloid-beta and phosphorylated tau—proteins commonly found in Alzheimer’s disease—in the bodies of Covid patients.
As I mentioned earlier, neurodegeneration is a somatic change, meaning it is organic disease. Earlier this year it was shown that Covid shrinks the overall volume of brain tissue and simultaneously increases cerebrospinal fluid. There is no easy fix for neurotropism.
Other factors could also be contributing, of course, such as neuroinflammation, which has been covered elsewhere. These factors all add up to a profoundly altered environment for the brain.
So, again, take simple measures. Mask up! Although Covid is an airborne disease, it does not hurt to wash hands frequently, and maintaining some distance socially might still be worthwhile (although at this point in the pandemic, most people have dropped this safety measure). Of course, after discussing with your doctor to see what’s the best course, I would add my vote toward getting vaccinated, also, if you haven’t already.
Forewarned is forearmed, yes? Enjoy your holiday season. Just be thoughtful. Remain vigilant!
References
- SARS-CoV-2 invades cognitive centers of the brain and induces Alzheimer’s-like neuropathology. Wei-Bin Shen et al., bioRxiv, 2022.
- SARS-CoV-2 infects neurons and induces neuroinflammation in a non-human primate model of COVID-19. Danielle Beckman et al., Cell Reports, 2022.
- Functional connectome analyses reveal the human olfactory network organization. T. Campbell Arnold et al., eNeuro, 2020.
- SARS-CoV-2 is associated with changes in brain structure in UK Biobank. Gwenaëlle Douaud et al., Nature, 2022.
- Structural and metabolic brain abnormalities in COVID-19 patients with sudden loss of smell. Maxime Niesen et al., European Journal of Nuclear Medicine and Molecular Imaging, 2021.
- Olfactory loss and brain connectivity after COVID-19. Fabrizio Esposito et al., Human Brain Mapping, 2022.
- The human entorhinal cortex: normal morphology and lamina-specific pathology in various diseases. Heiko Braak and Eva Braak, Neuroscience Research, 1992.
- Absent Blood Oxygen Level-Dependent Functional Magnetic Resonance Imaging Activation of the Orbitofrontal Cortex in a Patient With Persistent Cacosmia and Cacogeusia After Covid-19 Infection. Ismail Ismail and Khaled Gad, JAMA Neurology, 2021.
- Magnetic Resonance Imaging Alteration of the Brain in a Patient With Coronavirus Disease 2019 (COVID-19) and Anosmia. Letterio Politi et al., JAMA Neurology, 2020.
- Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation. Anthony Fernandez-Castaneda et al., Cell, 2022.
- Entorhinal Cortex and Persistent Olfactory Loss in COVID-19 Patients: A Neuroanatomical Hypothesis. Comment on Fiorentino et al. Correlations between Persistent Olfactory and Semantic Memory Disorders after SARS-CoV-2 Infection. Pietro de Luca et al., Brain Sciences, 2022.
