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Taking a Closer Look at COVID-19’s Effects on the Brain

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MRI of a brain damaged by COVID-19
Caption: Magnetic resonance microscopy showing lower part of a COVID-19 patient’s brain stem postmortem. Arrows point to light and dark spots indicative of blood vessel damage with no signs of infection by the coronavirus that causes COVID-19. Credit: National Institute of Neurological Disorders and Stroke, NIH

While primarily a respiratory disease, COVID-19 can also lead to neurological problems. The first of these symptoms might be the loss of smell and taste, while some people also may later battle headaches, debilitating fatigue, and trouble thinking clearly, sometimes referred to as “brain fog.” All of these symptoms have researchers wondering how exactly the coronavirus that causes COVID-19, SARS-CoV-2, affects the human brain.

In search of clues, researchers at NIH’s National Institute of Neurological Disorders and Stroke (NINDS) have now conducted the first in-depth examinations of human brain tissue samples from people who died after contracting COVID-19. Their findings, published in the New England Journal of Medicine, suggest that COVID-19’s many neurological symptoms are likely explained by the body’s widespread inflammatory response to infection and associated blood vessel injury—not by infection of the brain tissue itself [1].

The NIH team, led by Avindra Nath, used a high-powered magnetic resonance imaging (MRI) scanner (up to 10 times as sensitive as a typical MRI) to examine postmortem brain tissue from 19 patients. They ranged in age from 5 to 73, and some had preexisting conditions, such as diabetes, obesity, and cardiovascular disease.
The team focused on the brain’s olfactory bulb that controls our ability to smell and the brainstem, which regulates breathing and heart rate. Based on earlier evidence, both areas are thought to be highly susceptible to COVID-19.

Indeed, the MRI images revealed in both regions an unusual number of bright spots, a sign of inflammation. They also showed dark spots, which indicate bleeding. A closer look at the bright spots showed that tiny blood vessels in those areas were thinner than normal and, in some cases, leaked blood proteins into the brain. This leakage appeared to trigger an immune reaction that included T cells from the blood and the brain’s scavenging microglia. The dark spots showed a different pattern, with leaky vessels and clots but no evidence of an immune reaction.

While those findings are certainly interesting, perhaps equally noteworthy is what Nath and colleagues didn’t see in those samples. They could find no evidence in the brain tissue samples that SARS-CoV-2 had invaded the brain tissue. In fact, several methods to detect genetic material or proteins from the virus all turned up empty.

The findings are especially intriguing because there has been some suggestion based on studies in mice that SARS-CoV-2 might cross the blood-brain barrier and invade the brain. Indeed, a recent report by NIH-funded researchers in Nature Neuroscience showed that the viral spike protein, when injected into mice, readily entered the brain along with many other organs [2].

Another recent report in the Journal of Experimental Medicine, which used mouse and human brain tissue, suggests that SARS-CoV-2 may indeed directly infect the central nervous system, including the brain [3]. In autopsies of three people who died from complications of COVID-19, the NIH-supported researchers detected signs of SARS-CoV-2 in neurons in the brain’s cerebral cortex. This work was done using the microscopy-based technique of immunohistochemistry, which uses antibodies to bind to a target, in this case, the virus’s spike protein. Also last month, in a study published in the journal Neurobiology of Disease, another NIH-supported team demonstrated in a series of experiments in cell culture that the SARS-CoV-2 spike protein could cross a 3D model of the blood-brain barrier and infect the endothelial cells that line blood vessels in the brain [4].

Clearly, more research is needed, and NIH’s National Institute of Neurological Disorders and Stroke has just launched the COVID-19 Neuro Databank/Biobank (NeuroCOVID) to collect more clinical information, primarily about COVID-19-related neurological symptoms, complications, and outcomes. Meanwhile, Nath and colleagues continue to explore how COVID-19 affects the brain and triggers the neurological symptoms often seen in people with COVID-19. As we learn more about the many ways COVID-19 wreaks havoc on the body, understanding the neurological symptoms will be critical in helping people, including the so-called Long Haulers bounce back from this terrible viral infection.

References:

[1] Microvascular Injury in the Brains of Patients with Covid-19. 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. N Engl J Med. 2020 Dec 30.

[2] The S1 protein of SARS-CoV-2 crosses the blood-brain barrier in mice. Rhea EM, Logsdon AF, Hansen KM, Williams LM, Reed MJ, Baumann KK, Holden SJ, Raber J, Banks WA, Erickson MA. Nat Neurosci. 2020 Dec 16.

[3] Neuroinvasion of SARS-CoV-2 in human and mouse brain. Song E, Zhang C, Israelow B, et al. J Exp Med (2021) 218 (3): e20202135.

[4] The SARS-CoV-2 spike protein alters barrier function in 2D static and 3D microfluidic in-vitro models of the human blood-brain barrier. Buzhdygan TP, DeOre BJ, Baldwin-Leclair A, Bullock TA, McGary HM, Khan JA, Razmpour R, Hale JF, Galie PA, Potula R, Andrews AM, Ramirez SH. Neurobiol Dis. 2020 Dec;146:105131.

Links:

COVID-19 Research (NIH)

Avindra Nath (National Institute of Neurological Disorders and Stroke/NIH)

NIH Support: National Institute of Neurological Disorders and Stroke; National Institute on Aging; National Institute of General Medical Sciences; National Cancer Institute; National Institute of Mental Health

7 Comments

  • Emmanuel Edokobi says:

    The question that comes to the mind of every prudent American would be whether the United States of America’s Frontline Health Experts at these noble institutions that include; NIH, CDC and DHHS are ready and willing to prepare medicines that should address these debilitating effects of Covid-19 on Americans.

    • Elsa S. says:

      We need to be sharing these articles and demanding this. I personally am having neurological symptoms after contracting covid over Thanksgiving. I still do not have all of my taste and smell and I experience frequent dizziness. It’s not spinning like vertigo but a definite warning for me. In regards to crossing the blood brain barrier strip has been wreaking havoc this way and no one is publicly calling attention to it. PANS or PANDAS is raking havoc on my godson. How are brain reacts to our DNA constantly mutating will NOT BE GOOD. Our future contains a lot of poison. We deserve acknowledgment and treatment… NOT SWEPT UNDER A RUG!

  • gardenabbess says:

    This evokes memories of my battle to regain my health after a bout of mononucleosis 50 years ago. I had persistent headaches with abdominal bloating. I gradually developed psych symptoms such as hearing disembodied voices. What finally worked for me after 12 years of pain was to have food allergy testing. I was very allergic to a lot of foods, including cereal grains. Removing those from my diet turned things around until perimenopause when I started to lose my grip again. As I aged into my 60s the clues started showing up. My thyroid is sensitive to thiols. A couple of years later, pancreatitis develops. I found I could manage it successfully by doubling down on a low thiol diet, not just kale/cole crops, but legumes, dairy, coffee and chocolate. So now I’m gluten-free, dairy-free and legume (soy) -free.

    My father had gout and while none of his offspring have gout, there’s a lot of thyroid problems and fibromyalgia. For myself, when I eliminated legumes, my cholesterol dropped from 425 to 250, I don’t have arthritis issues and I haven’t felt as good as when I was a teenager, thanks to a better functioning thyroid. Another thing I discovered while scoping out my health problems was that both my parents had a copy of the A1298C mutation because I have two.

    I’m telling you this because it’s what you don’t know that gets you every time. My hypothesis is that my viral infection sensitized me to thiol-bearing proteins, and that these proteins are the essence of autoimmunity. Because both my thyroid and my pancreas were kicking back at me, one has to consider that this sensitivity could involve the entire endocrine system.

    Little clues that don’t seem to make sense are the clues that are telling the story. Pay attention to family medical history and new protein (food and airborne) intolerances. COVID-19 is a nasty mystery of a disease and I fear its persistence. We are all in it for the long haul. But the discoveries we make going forward will change medicine for the better.

  • Stefan Geier says:

    Excellent science for our benefit! I’m reminded on works on HIV-related microvascular changes associated with neurological, neuropsychological, ophthalmic, and neuroophthalmic etc deficits we studied two decades ago (see Geier S et al: AJO, GJO, AIDS, BrJO etc.). #COVID19 patients might benefit from reception of our research, eg haemorheological, and endothelial (Endothelin, NO) aspects. (Additum: We had a tiny cooperation with R Gallo at NIH.)

  • Samantha G. says:

    I had Covid over Christmas and New Years. It was a very mild case from a symptom standpoint. I had a low grade fever for a day, some sinus pressure, and a mild cough. Now that I’m out of quarantine, however, I have issues with vertigo, headaches, hand tremors, and (the strangest last effect for me) I cannot sneeze. Anyone else out there who can no longer sneeze?

  • Gladys L. says:

    Okay I’m a long hauler and the effects of brain fog, concentration and memory are lingering daily. This has caused me to be out of work from January 16th til this date. I have trouble just cooking a meal and keeping concentration on that. Any ideas on what to do about this?

  • johnnie says:

    Is there anybody else who has had covid-19 and developed internal tremors, blurred vision, and a nagging pain in the chest that has nothing to do with your heart. I have been dealing with these issues since the end of October

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