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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.


[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.


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


  • 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!

      • Steven R. says:

        I have just now, after 14 days of covid infection, received a negative test result. Why am I sitting here at 1:00 am instead of finally relaxing in bed and enjoying a little worry free nap? Well, I’m exhausted but can’t sleep, pain in the lower back of my neck, can’t keep a rational thought in my brain, equilibrium has decided to take a break, I’ve developed a minor tremble inside my torso with a weakened way of moving around, and blurred vision that comes and goes. I have a pre-existing head injury that caused me to become epileptic in. 1996. I take 500 mg. of Dilantin per day to control my seizures . This might be a bit of a stretch for a question, but, can anyone out there relate to this at all?? If so, could you reply to let me know that I’m not alone, because I’m about to short circuit trying to explain this to people. Please and thank you.

        • Shirley L. says:

          I also had covid19 in Dec.2020. I had long term effects…brain fog fatigue, pain everywhere.
          I have had epilepsy from a car accident in 1989.
          My primary care dr. said I should get the vaccine. I got the Pfizer vaccine with no problems then got the second a few weeks later, after the second I expected to have flu-like symptoms but instead started feeling like my old self again. I still don’t have much of an appetite but try to make sure I keep my weight up. Sometimes I feel dizzy. I take Keppra ER for my seizures plus CBD oil. I haven’t had any seizures since on the Keppra and CBD oil. I have to be careful so I don’t overdo now or I pay the price the next day with my joints aching.
          I realize I should have died from the covid19 because I am 85 years old. I spent a few times in the hospital and also had pneumonia. I guess I am one tough cookie!!!!
          Stay strong and hope for the best!!

        • Lee L. says:

          I feel the same way. I’m confused and I’m exhausted and I cannot sleep. I wake up, I fall asleep, but then I wake up and have a hard time going back to bed unless I take all kinds of medicine. Feel free to answer me or contact me anytime you want to? I think the cognitive problems are the worst and the exhaustion.

      • Lynn perry says:

        Does anyone know if spike proteins can be transferred and what the symptoms are?

  • 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?

    • Shirley L says:

      I also was a long hauler. I had the vaccine and got better but I still have some issues likeshortness of breath and lack of taste.

      • T says:

        I spend time thinking about receiving the vaccine but I am worried everything could get worse. Tinnitus, concentration, memory, balance, mood, energy, hold on let me check my notes, vision etc…

  • 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

    • KAL says:

      I had Covid in early February. It was a mild case. Two weeks ago, I started feeling like my left leg had some circulation issues. Now, the left, upper, inner thigh and pelvic area are vibrating. It’s not something I can feel from the outside, only internally. When I brought the issues up to my doctor, he acted like it wasn’t that big of a deal. Did your tremors go away? They keep me up at night. I otherwise feel fine but this constant vibrating is driving me crazy.

    • Linn says:

      Sounds like you may have acid reflux/gurd. There is a strange feeling in the chest. A pressure. Not the burning pain that anacid commercials predict. I do hope it is gurd b/c you can do something to fix that.

  • Mason says:

    I had covid,& never had symptom…one morning went numb..month later,had stroke….after cat scan.they told me had tumor on thalamus…meanwhile my feet swelled.with serious pain…to no available diagnosis yet….a follow up mri, revealed the “tumor” on brain has all but gone away…. tho still numb on right side.pain in feet..and seeing at least 6 different doctors..still no diagnosis… but tested positive for covid antibodies….. anyone experience anything remotely the same????

    • Thurlo Tim B. says:

      I have no reason to lie or otherwise. Took the Pfizer made me physically a touch I’ll. Went away and they had the most intense adverse physical effects, one could every believe. In addition of not sleeping 3 days or eating. COULD Not put two words together. Motor control down 50% this is barely the tip of the ice berg. Please help with advice. Can barely form the correct words much less than sentence. I feel like I have had a stroke. For day I slurred like 2 many Valium. Days of no sleep all my friends and family ask if I had used meth. No I’m not getting better. Feel like it changed me and I’ll never be me again.

      • Miriya says:

        That’s messed up. I’m sorry. I feel like that as well now, 8 days after second dose. Not that bad, but getting there. This is seriously messed up. Where in the US do you live?

  • Kathy W, says:

    I contacted covid-19 in mid October. No taste or smell, fatigue, short term memory loss, confusion and blurred vision at different times of the day. At this time all still exist, however, my loss of taste and smell has changed. I open a jar of peanut butter and can smell something but not peanuts. Nothing smells the same. Also, did anyone notice a change of temperature? I was always 98.6 till covid. I’m in the 97 count. I want my temperature back to normal along with everything else.

    • Janet S says:

      I am having the same exact issues. Mid Oct I also had covid and lost had the same issues you list. FInally now, Sept. 2022 I am getting taste back but it is off. My smell is still gone. I go from being cold to over heated several times a day and I am exhausted but have insomnia at night. My largest concern though….brain fog. I am struggling with transposing numbers and doing my day to day normal tasks. I see more and more comments, Lets hope someone chimes in with some help soon!

  • Pauline T. says:

    My 95 year old mother who lives in a Nursing Home, got Covid 19 at the end of January and was put on an isolated unit with others. She now has memory problems, personality changes, gets angry at the staff, will throw things around, cries and sobbing a lot, suspicious of what is going on, thinks the staff is playing tricks on her, swears-which she never did before, can’t walk with her walker, have to use a Hoyer lift which causes her discomfort, if touched at times she cries out in pain, anxious where I worry she will have a stroke or heart attack, calls me up to 25 or more times per day and more. How do I deal with this and also the poor staff taking care of her? They have put her on Lexepro 5mg daily, which was started last Saturday am. That takes 6 weeks to get into her system. She did get an IV med that was recommended to help her on her second day of being on the unit. The name of the med is Bamlanivimab. I gave them permission to do so and at times I feel guilty that I did so as reading up on the drug, it can cause confusion. Is there anything that can help her? Thank you in advance for answering and guiding me.

    • Megan Joyner says:

      Pauline, Have them first test for a urinary tract infection. They cause confusion in the elderly with sometimes little or no side effects, second speak to the doctors abt the lexapro, it may be making her feel bad. I did better with Zoloft bachelor lexapro made me feel so crazy and confused, and there are other better ones. Make sure she’s taking a calcium magnesium zinc multivitamin combo to help with the transition of starting her new antidepressant.

    • Chandra Zinola says:

      Pauline, my mother has Alzheimer’s and early on, she had a lot of anger, throwing things, etc. My father and I were devastated. Her Neurologist prescribed Depakote, actually for sleep, but it was a miracle med. for the anger! (250mg, initially; then increased to 500 mg). It worked amazingly well and fortunately, with none of the listed side effects. That was in 2018 and she continues to do well. She was already taking Pristiq for depression/anxiety. She is currently 83. I am SO sorry for what you are going through with your Mom. I am not a doctor, but my guess is that the isolation brought on most of your Mom’s symptoms. I pray that once a couple of these medications kick in, she will get back to normal. By the way, Depakote is not an antidepressant, so it should not take 6 weeks to be effective. All the best to you and your Mom. Many Blessings.

  • Lorez M. says:

    I started having weak legs and the feeling as if my collar needed to be loosened back in 2018. I began having difficulty keeping my body from bending toward the front. This continues while more concerns began, since last year I’ve hardly been able to walk given tremors in legs mostly, but all over if I over exert myself. I keep brain fog and I wonder do I have covid antibodies from an unaware exposure.

  • Geff says:

    Has anyone experienced an overwhelming smell of smoke . It is driving my wife crazy. Any treatment advice would be appreciated.

    • Linn says:

      Geoff- the smell of smoke or burning can be due to her medications. Especially depression medication like Effexor. Start there.

    • Leigh says:

      Geff….one of my first symptoms of Covid19 was “smelling smoke/something burning”. It was the exact odor. Of course, no one else smelled it.

      • Miriya says:

        That’s a sign of a stroke, smelling smoke. Please go get checked ASAP.

      • Kate says:

        I believe I had Covid January 2020. No tests were available yet so I was never tested, but at the time my doctors called it a 3 week coughing virus. My sense of smell is still not normal. Meat smells rotten to me, most especially pork, but beef also. That’s before I cook it, but even after cooking I can’t stomach the smell or taste of it. I did not have this issue prior to Covid.

  • Elizabeth G says:

    I had cov in January for 6 weeks it is now March 26th and i am back to work but I can’t take the pain in the left side of my head anymore the doctor has gave me solpadol 30mg/500mg nothing is helping why

  • Lynn N. says:

    My 39-year-old daughter had COVID in December. She has a speech problem, memory problems, concentration problems, headaches.
    What is the cure? Will she get better with time? So sad…..

    • Hambone says:

      I,too, tested positive for COVID this past December. Gradually after, noticed increased difficulty enunciating. But I’m old, so, who knows…

  • Jennifer M says:

    I was initially diagnosed with COVID in November and continue to test positive… got dubbed a “long hauler”. My most annoying symptom has been on going restless leg syndrome and inability to sleep, let alone that cognitive decline. I had a severe TBI many years ago, but with COVID, it feels like I’m reliving the trauma all over again!

  • Laura H. says:

    If the SARS CoV2 spike proteins alone can cause these problems (weakening of the blood-brain barrier, inflammation in the brain, thickening of blood vessel walls, etc.), I am wondering why the mRNA vaccines’ spike proteins are considered “harmless” (according to the CDC). Is this a matter of quantity? In other words, do the vaccines lead to only a relatively small number of these spike proteins circulating (small in comparison to the amount present from a COVID infection), so that there just aren’t enough spike proteins to create these negative effects in the brain and blood vessels? Or is this more of a matter of the risks outweighing the benefits–i.e. the risks of vaccine spike proteins are small compared to risks from COVID infection–so that the vaccines are still considered the best option? Either way, I don’t understand why the vaccine-produced spike proteins are considered “harmless.” Could someone with a medical/biochem background help clarify this for me?

  • Kathy Barnett says:

    Ketamine shot for the brain inflammation encephalitis caused from COVID 19 will help

  • T says:

    Very true for myself. I contracted this virus in November 2019 here in the US. My life changed and has not recovered. I had an MRI done in December 2019 and nothing was found. All doctors pointed at PVI. Very upset with the medical field and how we have no vital recovery methods for this problem I have.

  • Tom says:

    I had Covid in September 2020. It started as a fever of 98-100.4 along with some stiffness in my back and neck. Day by day it got much worse; the pain in my back was so bad I could barely walk or turn over in bed. I couldn’t even put on my socks! The pain bordered on paralysis – it was hard to move at all. After about a week the symptoms slowly disappeared, leaving me weak with that Covid “fog” and some dizziness. Now I have the same symptoms all over again, back pain that moves from the lower back to between the shoulder blades. I used Thermacare wraps on my back and CBD gummies to deal with the pain. I have been vaccinated 2x with the Pfizer vaccine but I wonder how many times I will go through this again. I’m not sure the doctors have realized all the neurological and nerve problems this virus can cause.

  • Rhonda says:

    My daughter experienced her first gran mal seizure March 1st 2021. She tested positive for covid 19 January 27th. I can’t help but think there is a connection between these two things. If covid can cause inflammation of the heart, surely it can cause inflammation of the brain. That’s why we can’t smell when we have covid … correct ?

  • Janice Z says:

    I had Covid in December 2020 that lasted for 20 days. I finally got over it, but had a slight drag in my left eye and some memory issues that got better. However, Feb 27, 2021 my world was changed forever. I woke up that morning with ringing in my left ear, headaches, hand tremors, stomach pain, fatigue, twitching eye and shaky legs. Later, I developed back problems, because I was pretty much stuck in bed. The doctors did find an eroded duodenum the second week of March. I am now being treated for depression and anxiety. I have been to the ER 11 times for chest pain, two hematomas, to begin with. I did have a heart stent in Sept of 2020, so the regular drugs are in place, such as: Aspirin, Plavix, Blood Pressure. There was a second minor blockage in September at 30%, which is now at 50 to 60%. Did the Covid accelerate the blockage? Since March 1st, I have have seen so many doctors, I have lost track. My ear is still ringing, the headaches are really bad, stomach spasms continue, tremors in my hands, shaky legs, fatigue, confusion, nausea, back pain and neck pain. I cry a lot and the anxiety is horrible. I am taking Ativan, which helps a little. Several of the doctors just say Covid brain give you a pill and move on. My husband was working from home, but is going to return back to work shortly. I can’t be left alone due to separation anxiety. I’m looking in to Adult Day Care. I am only 61 and this stuff has left me almost unable to take care of myself. I am seeing someone for talk therapy. What is wrong with me? If you have any information, please share. Some days I feel like this is never going to end.

    • Louise S. says:

      Janice Z, nothing is wrong with you, just with your body, which took a severe dislike to covid, heart disease, etc, and the crying is probably a valid stress reaction. When the immune system gets triggered, it can accelerate other health issues, such as your heart issues. Stress hormones your body makes normally can affect cardiac problems such as blockage. My psoriasis (autoimmune) is familial, but became much worse after a “strange illness” in January 2020, when covid was not supposed to be here yet, so have never had a positive covid test, am vaccinated, and do have good antibodies now.
      Tinnitus, psoriatic arthritis, weakness, low tolerance to activity, new onset headaches, nausea, neck and back pain, muscle spasms, stressed, blurry vision, brain fog, dizzy spells…welcome to the club I joined that month. I changed my diet to eliminate foods that trigger inflammation which helped some of my symptoms, lowered my cholesterol and blood sugar, but not all the inflammatory reactions. My ears are ringing loudly all the time. And yes, I am more moody than I used to be.

      Be sure to check all the side affects of every medication you are on with your pharmacist. Sometimes meds for one problem can trigger other problems or interact with other meds you are taking, and some can cause depression or anxiety. My latest med for the inflammation doubled the intensity of my headache and made it last 18 hours, only stopping then because I stopped the med at my doctor’s direction when it caused me problems.

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