Patients hospitalised for COVID-19 had higher levels over the short term of blood proteins known to rise with neurological damage than non–COVID-19 patients diagnosed with Alzheimer’s disease, a new study has found.
The research – conducted over two months early in the COVID-19 pandemic – found higher levels of seven markers of brain damage, or neurodegeneration, in patients with COVID-19 with neurological symptoms than those without them, and much higher levels in patients that died in the hospital than in those discharged and sent home.
A second analysis by the team from NYU Grossman School of Medicine found that a subset of the damage markers in patients hospitalised with COVID-19, over the short term, were significantly higher than in patients diagnosed with Alzheimer’s disease, and in one case more than twice as high.
“Our findings suggest that patients hospitalised for COVID-19, and especially in those experiencing neurological symptoms during their acute infection, may have levels of brain injury markers that are as high as, or higher than, those seen in people who have Alzheimer’s disease,” says lead author Dr Jennifer A. Frontera, professor in the Department of Neurology at NYU Grossman School of Medicine.
“Traumatic brain injury, which is also associated with increases in these biomarkers, does not mean that a patient will develop Alzheimer’s disease or related dementias later on, but does increase the risk of it,” says senior author Dr Thomas M. Wisniewski, the Gerald J. and Dorothy R. Friedman Professor in the Department of Neurology and director of the Center for Cognitive Neurology at NYU Langone.
“Whether that kind of relationship exists in those who survive severe COVID-19 is a question we urgently need to answer with ongoing monitoring of these patients.”
The study, conducted from March to May 2020, identified 251 people who, although 71 years on age on average, had no record or symptoms of cognitive decline or dementia before being hospitalised for COVID-19.
These patients were then divided into groups with and without neurological symptoms during their acute COVID-19 infection, when patients either recovered and were discharged, or died.
The research team also, where possible, compared marker levels in the COVID-19 group to patients in the clinical core cohort of NYU Langone’s Alzheimer’s Disease Research Center, an ongoing, long-term study at NYU Langone Health.
None of these 161 control patients (54 cognitively normal, 54 with mild cognitive impairment, and 53 diagnosed with Alzheimer’s disease) had COVID-19. Brain injury was measured using single-molecule array (SIMOA) technology, which can track the minute blood levels of neurodegeneration markers in picograms (one trillionth of a gram) per millilitre of blood (pg/ml), where older technologies could not.
Three of the study markers—ubiquitin carboxy-terminal hydrolase L1 (UCHL1), total tau, and phosphorylated-tau-181 (ptau181)—are known measures of the death or disabling of neurons, the cells that enable nerve pathways to carry messages.
Levels of neurofilament light chain increase with damage to axons, which are extensions of neurons. Glial fibrillary acidic protein (GFAP) is a measure of damage to glial cells, which support neurons. Amyloid beta 40 and 42 are proteins known to build up in people who have Alzheimer’s disease.
Past study results argue that total tau and ptau181 are also specific measures of Alzheimer’s disease, but their role in the disease remains a matter of debate.
Blood markers in the COVID-19 patient group were measured in blood serum (the liquid part of blood that has been made to clot), while those in the Alzheimer’s disease study were measured in plasma (the liquid blood fraction that remains when clotting is prevented).
For technical reasons, the difference meant that neurofilament light chain, GFAP, and UCHL1 levels could be compared between the COVID-19 group and patients in the Alzheimer’s disease study, but total tau, ptau181, amyloid beta 40, and amyloid beta 42 could only be compared within the COVID-19 patient group (neuro symptoms or not; death or discharge).
Further, the main measure of neurological damage in patients with COVID-19 was toxic metabolic encephalopathy, or TME, with symptoms that range from confusion to coma, and caused during severe infections by toxins generated as the immune system overreacts (sepsis), kidneys fail (uremia), and oxygen delivery is compromised (hypoxia).
Specifically, the average percentage increase in levels of the seven markers for hospitalised patients with TME compared to those without neurological symptoms was 60.5 per cent.
For the same markers within the COVID-19 group, average percentage increase when comparing those successfully discharged home from the hospital to those who died in the hospital was 124 per cent.
A secondary set of findings came from comparing neurofilament light chain, GFAP, and UCHL1 levels in the serum of people with COVID-19 against levels of the same markers in the plasma of non–COVID-19 Alzheimer’s disease patients.
Neurofilament light chain was, over the short-term, 179 per cent higher (73.2 versus 26.2 pg/ml) in patients with COVID-19 than those with Alzheimer’s disease. GFAP was 65 per cent higher (443.5 versus 275.1 pg/ml) in patients with COVID-19 patients than those with Alzheimer’s disease, while UCHL1 was 13 per cent higher (43 versus 38.1 pg/ml).
‘See the hidden me after brain injury’
Action for Brain Injury Week highlights the struggle of survivors to adapt to the ‘invisible’ effects of brain injury
More than three quarters of brain injury survivors experience problems on a daily basis as a result of their hidden disabilities, new research has revealed.
In Action for Brain Injury Week, the reality for survivors is laid bare through new research from Headway, which reveals 76 per cent experience problems every day as a direct consequence of their brain injury being ‘invisible’.
Further findings reveal:
- More than half (55 per cent) of brain injury survivors feel they have been unfairly treated as a direct consequence of their brain injury being hidden
- Two thirds of friendships (67 per cent) and more than half (55 per cent) of relationships with a spouse/ partner have been negatively affected as a direct consequence of the brain injury being hidden
- 86 per cent of people affected by brain injury (survivors and carers) felt that a lack of understanding from society is one of the main challenges to living life with a hidden disability.
To help raise awareness of the hidden, and often misunderstood, consequences of brain injury, Headway has launched its See The Hidden Me campaign, which shows the battle that survivors and their carers, families and loved ones face to adapt to life.
One survivor, Christine Charles, was diagnosed with a brain tumour in 2014 and underwent numerous surgeries and procedures in her eight-year cancer battle that initially left her unable to walk or talk.
“I was alive and I was walking and talking. And whilst it was the end of that chapter, it’s not the end of the story because there are so many side effects,” she says.
It is now the hidden disabilities that Christine, and her wider caring network, struggle with – her memory, her agitation and the assumption that she’s now ‘well’ which she believes negates the long-term damage that’s been caused to her brain.
“Don’t expect me to be better,” she says.
“It took me a long time to realise I will never be better. That’s fine. I’m ok with that.
“But I think some people [struggle], ‘Well when will you be better? Oh, do you still need that [Headway]? But in the politest of ways, I am never going to be better.”
Christine features in this year’s See the Hidden Me campaign film alongside three other survivors John, Iona and Annette.
In the video they share the very real-life ways the hidden effects of their brain injuries, including memory loss, fatigue and difficulties concentrating, may be perceived, and explain their wish to be given a little more time, a little more understanding, and a little less judgement.
Their message: ‘Be kind. Be patient. Don’t misread the signs. See the Hidden Me’
Their sentiments are echoed by some of the 2,682 respondents to the See the Hidden Me study which reflected the emotional toll it can take on the survivor and their wider caring network.
‘People judge you as a normal person with no issues as that is how I look. They literally judge a book by its cover.” – Stephen
“When I tried to return to work folks would just see I looked fine and one even told me I’d “be fine, you look great” like that’s some kind of good thing when there’s a million symptoms kicking that no-one can see.” – Jodie
“Friends have given up on me because I can’t do all the fun stuff they do.” – Rebecca
Peter McCabe, Headway’s chief executive, said: “The results of this study demonstrate the difficult path survivors, and their carers, tread post-brain injury.
“To see the scale of the struggle endured by those with a hidden disability, not just a couple of years after injury, but decades later, makes depressing reading. The results of this survey are a call to action and should make us all more determined to do better.
“Brain injury can happen to anyone at any time, and when it does, Headway is here to help.
“We need to listen to the voices of these survivors and carers to be more patient, to listen, not to judge or undermine, and to educate ourselves about the long-term impact a brain injury can have on every bit of a person’s life.”
Concussion Legacy Foundation tackles media coverage of concussion
CLF worked with BT Sport on a world-first project in training staff in reporting on concussion
The Concussion Legacy Foundation (CLF) is continuing its commitment to changing the way head injury and concussion is viewed in sport by introducing a world-first media training initiative into the UK.
The CLF has worked with BT Sport on its Concussion Reporting Workshop PRO, a first-of-its-kind program to educate its team in how to report on concussion. The broadcaster involved its cricket, boxing, football and rugby reporting and production teams in the initiative.
The workshops, part of the CLF Media Project – the first and only concussion education program designed specifically for sports media members – were presented by CLF co-founders Dr Robert Cantu and Dr Chris Nowinski, and helped to address areas including the basics of concussion, the dos and don’ts of reporting on concussion, and the importance of concussion reporting to educate hard-to-reach coaches, parents, and athletes.
The program has been used successfully by broadcasters and journalists across the United States, and has played a key role in redefining the way concussion is reported and regarded.
Dr Nowinski has previously spoken to NR Times about the importance of challenging the traditional approach of many media outlets in ‘glorifying’ players returning to action after head injury.
Now, through its introduction into the UK, its commitment to changing attitudes, and as a result the future for players of all levels, is increasing further still.
“The UK is many years behind the US in terms of understanding and dealing with concussion in sport,” said Dr Adam J. White, executive director of CLF UK.
“It is great that an organisation as influential as BT Sport is taking this step to educate their team on the proper standards for concussion coverage and shows tremendous leadership on responsible reporting.
“Every concussion on TV is an opportunity to educate, so when a commentator highlights the importance of concussion, it reinforces to every spectator, athlete, kid, and parent why we should be taking concussions seriously.”
“Improving our understanding and research into concussion in sport is a subject that I am hugely passionate about, and whilst it is extremely important that we understand the impact in training, in the game and on our bodies, we the sports media can also play our part in ensuring that we report and describe concussion and head impacts correctly, so that our viewers understand what they are seeing on the field and the correct response,” said Ben Kay, rugby analyst for BT Sport.
“The presentation taught us how to cover the injury while still dealing in facts, something which I would encourage all sports broadcasters to invest their time in learning about.”
CLF launched the Media Project, which includes three parts: a Concussion Reporting Certification for sports media professionals, a Concussion Reporting Workshop for sports journalism students, and the Concussion Reporting Workshop PRO for sports media outlets, in 2018.
Sports media veterans J.A. Adande, Bob Costas, Andrea Kremer, and Olivia Stomski helped CLF create the curriculum for the Media Project and serve as advisors for the program.
More than 140 sports media professionals are now Concussion Reporting Certified, and the Concussion Reporting Workshop has been taught in 54 classes at 24 schools in the US and UK including St. Mary’s University Twickenham and Bournemouth University.
Can concussion clues come from the gut?
Through blood, stool and saliva samples, a new study has examined the diagnostic potential of the gut’s microbiome
Indicators of concussion could be found in the gut, giving new levels of insight into its impact and when it may be safe to return to action, new research has revealed.
By taking blood, stool and saliva samples, a new study was able to examine the diagnostic potential of the gut’s microbiome.
The research, conducted with 33 Rice University footballer players over the course of one season, found a post-concussion drop-off of two bacterial species normally found in abundance in stool samples of healthy individuals.
It also found a correlation between traumatic brain injury linked proteins in the blood and one brain injury linked bacterial species in the stool.
After a concussion, the injuries cause inflammation, sending small proteins and molecules circulating through the blood that breach the intestinal barrier and cause changes in the gut, affecting metabolism.
The Houston Methodist research said these changes in the microbiota can deliver vital clues to help safeguard the person and their recovery.
“Until your gut microbiome has returned to normal, you haven’t recovered,” said Dr Sonia Villapol, assistant professor of neurosurgery at the Center for Neuroregeneration in the Houston Methodist Research Institute.
“This is why studying the gut is so useful. It doesn’t lie. And that is why there is so much interest in using it for diagnostic purposes.”
While brain movement within the skull may cause injury to nerve cells, such microscopic cellular injuries are not visible on imaging tests like X-rays, CT scans and MRIs, which are more capable of finding injuries on the scale of skull fractures, brain bleeding or swelling.
As a result, the most commonly used test for diagnoses of concussions relies on self-reported symptoms like blurry vision, dizziness, nausea and headaches, which can be very vague, subjective and often underreported by athletes who want to continue playing. This can make them notoriously difficult to diagnose.
While there have been dozens of brain injury biomarkers identified, there has been limited success in developing commercial blood tests sensitive enough to detect tiny increases in biomarker concentrations, although a saliva test has been found to be effective.
However, due to the fact the central nervous system is intimately linked to the enteric nervous system, this could provide new insight, Dr Villapol said.
While only four of the players in the study were diagnosed with major concussions, the researchers say the results will need to be confirmed in a larger sample size.
They also plan to conduct a similar study soon among women in sport, who similarly have frequent head trauma.
“Women and men don’t have the same immunities or gut microbiomes, and as a woman and a mother of daughters, I would hate to be that researcher who only looks at men’s issues while overlooking women,” Dr Villapol said.
“Women soccer players have very high rates of concussions, as well, and all the same problems when it comes to existing diagnostic methods.”
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