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COVID-19 infections

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 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


Study of Healthcare Workers Shows COVID-19 Immunity Lasts Many Months

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Healthcare Workers
Credit: iStock/SelectStock

Throughout the COVID-19 pandemic, healthcare workers around the world have shown willingness to put their own lives on the line for their patients and communities. Unfortunately, many have also contracted SARS-CoV-2, the coronavirus that causes of COVID-19, while caring for patients. That makes these frontline heroes helpful in another way in the fight against SARS-CoV-2: determining whether people who have recovered from COVID-19 can be reinfected by the virus.

New findings from a study of thousands of healthcare workers in England show that those who got COVID-19 and produced antibodies against the virus are highly unlikely to become infected again, at least over the several months that the study was conducted. In the rare instances in which someone with acquired immunity for SARS-CoV-2 subsequently tested positive for the virus within a six month period, they never showed any signs of being ill.

Some earlier studies have shown that people who survive a COVID-19 infection continue to produce protective antibodies against key parts of the virus for several months. But how long those antibodies last and whether they are enough to protect against reinfection have remained open questions.

In search of answers, researchers led by David Eyre, University of Oxford, England, looked to more than 12,000 healthcare workers at Oxford University Hospitals from April to November 2020. At the start of the study, 11,052 of them tested negative for antibodies against SARS-CoV-2, suggesting they hadn’t had COVID-19. But the other 1,246 tested positive for antibodies, evidence that they’d already been infected.

After this initial testing, all participants received antibody tests once every two months and diagnostic tests for an active COVID-19 infection at least every other week. What the researchers discovered was rather interesting. Eighty-nine of the 11,052 healthcare workers who tested negative at the outset later got a symptomatic COVID-19 infection. Another 76 individuals who originally tested negative for antibodies tested positive for COVID-19, despite having no symptoms.

Here’s the good news: Just three of these more than 1400 antibody-positive individuals subsequently tested positive for SARS-CoV-2. What’s more, not one of them had any symptoms of COVID-19.

The findings, which were posted as a pre-print on medRxiv, suggest that acquired immunity from an initial COVID-19 infection offers protection against reinfection for six months or maybe longer. Questions remain about whether the acquired immunity is due to the observed antibodies alone or their interplay with other immune cells. It will be important to continue to follow these healthcare workers even longer, to learn just how long their immune protection might last.

Meanwhile, more than 15 million people in the United States have now tested positive for COVID-19, leading to more than 285,000 deaths. Last week, the U.S. reported for the first time more than 200,000 new infections, with hospitalizations and deaths also on the rise.

While the new findings on reinfection come as good news to be sure, it’s important to remember that the vast majority of the 328 million Americans still remain susceptible to this life-threatening virus. So, throughout this holiday season and beyond—as we eagerly await the approval and widespread distribution of vaccines—we must all continue to do absolutely everything we can to protect ourselves, our loved ones, and our communities from COVID-19.

Reference:

[1] Antibodies to SARS-CoV-2 are associated with protection against reinfection. Lumley, S.F. et al. MedRxiv. 19 November 2020.

Links:

Coronavirus (COVID) (NIH)

Combat COVID (U.S. Department of Health and Human Services, Washington, D.C.)

David Eyre (University of Oxford, England)


Masks Save Lives

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Masks save lives

Reminding others that “masks save lives” isn’t just sound advice. It’s a scientific fact that wearing one in public can help to slow the spread of SARS-CoV-2, the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic.

I’m very careful to wear a mask outside my home whenever I’m out and about. I do it not necessarily to protect myself, but to protect others. If by chance I’ve been exposed to the virus and am currently incubating it, I wouldn’t want to spread it to other people. And any of us could be an unknowing superspreader. We owe it to everyone we encounter, especially those who are more vulnerable, to protect them. As my NIH colleague Tony Fauci recently demonstrated, it’s possible to wear your mask even while you’re outside exercising.

But there are still skeptics around. So, just how much does a facial covering protect those around you? Quite a bit, according to researchers who created a sophisticated mathematical model to take a more detailed look [1]. Their model shows that even if a community universally adopted a crude cloth covering that’s far less than 100 percent protective against the virus, this measure alone could significantly help to reduce deaths.

These findings, funded partly by NIH, were published recently in Nature Communications. They come from Colin Worby, Broad Institute of MIT and Harvard, Cambridge, MA, and Hsiao-Han Chang, National Tsing Hua University, Taiwan.

The researchers noted several months ago that recommendations on wearing a mask varied across the United States and around the world. To help guide policymakers, the researchers simulated outbreaks in a closed, randomly interacting population in which the supply and effectiveness of crude cloth or disposable, medical-grade masks varied.

Under different outbreak scenarios and mask usages, the researchers calculated the total numbers of expected SARS-CoV-2 infections and deaths from COVID-19. Not surprisingly, they found that the total number of deaths and infections declined as the availability and effectiveness of face masks increased.

The researchers’ model primarily considered the distribution of medical-grade, surgical masks. But because such masks are currently available in limited supply, they must be prioritized for use by health care workers and others at high risk. The researchers go on to note that the World Health Organization and others now recommend wearing homemade face coverings in public, especially in places where the virus is spreading. While it’s true the ability of these face coverings to contain the virus is more limited than medical-grade masks, they can help and will lead to many fewer deaths.

Another recent paper also suggests that while wearing a mask is primarily intended to prevent the wearer from infecting others, it may also help lower the dose, or inoculum, of SARS-CoV-2 that the wearer might receive from others, resulting in milder or asymptomatic infections [2]. If correct, that’s another great reason to wear a mask.

Already, more than 175,000 people in the United States have died from COVID-19. The latest estimates [3] from the Institute for Health Metrics and Evaluation (IHME) at the University of Washington’s School of Medicine, Seattle, predict that the COVID-19 death toll in the U.S. may reach nearly 300,000 by December 1.

But that doesn’t have to happen. As this new study shows, face coverings—even those that are far from perfect—really can and do save lives. In fact, IHME data also show that consistent mask-wearing—starting today—could save close to 70,000 lives in the months to come. Saving those lives is up to all of us. Don’t leave home without your mask.

References:

[1] Face mask use in the general population and optimal resource allocation during the COVID-19 pandemic. Worby CJ, Chang HH. Nat Commun. 2020 Aug 13;11(1):4049.

[2] Masks Do More Than Protect Others During COVID-19: Reducing the Inoculum of SARS-CoV-2 to Protect the Wearer. Gandhi M, Beyrer C, Goosby E. J Gen Intern Med. 2020 Jul 31.

[3] New IHME COVID-19 forecasts see nearly 300,000 deaths by December 1. Institute for Health Metrics and Evaluation. August 6, 2020.

Links:

Coronavirus (COVID-19) (NIH)

Colin Worby (Broad Institute of MIT and Harvard, Cambridge, MA)

Hsiao-Han Chang (National Tsing Hua University, Taiwan)

NIH Support: National Institute of Allergy and Infectious Diseases