Friday, January 27, 2023

Neuron: Virus Exposure and Neurodegenerative Disease Risk Across National Biobanks


Influenza B Virus - Credit NIH Image Gallery

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Although it has gained renewed attention due to persistent reports of large numbers of COVID survivors continuing to experience `Post-COVID' sequelae (aka `Long COVID'), scientists have long suspected a link between viral infections and neurodegenerative (and other chronic) diseases. 

One hundred years ago the world experienced a mysterious epidemic in the decade following the 1918 influenza pandemic; a devastating neurological disease called Encephalitis Lethargica (EL) 

It has been estimated that as many as 5 million people were afflicted with EL between 1917 and 1927 -  and while roughly 1/3rd died during the acute phase of the illness - many of the survivors would go on to develop Parkinsonian features and other profound neurological sequelae, often years later. 

While some scientists suspect this disease to be a rare sequelae of the 1918 pandemic virus, a 2012 study presented a case for the EL epidemic having been caused by an enterovirus (see Evidence for an enterovirus as the cause of encephalitis lethargica). 

But the exact cause remains unknown.

Throughout history, there have been reports of similar outbreaks, resulting in severe neurological disease, including febris comatosa which sparked a severe epidemic in London between 1673 and 1675, and in 1890 in Italy, in the wake of the 1889–1890 influenza pandemic, a severe wave of somnolent illnesses (nicknamed the "Nona") appeared.

Among those who survived, Parkinsonism and other neurological sequelae was common.

Early in the COVID pandemic, we saw a number of cautionary reports based - at least in part - on those aftermaths, including:

Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms

by Emily A. Troyer, Jordan N. Kohn, and Suzi Hong.

COVID-19: can we learn from encephalitis lethargica?

Antonino Giordano, Ghil Schwarz, Laura Cacciaguerra, Federica Esposito, Massimo Filippi
Published:July, 2020
DOI:https://doi.org/10.1016/S1474-4422(20)30189-7

Even as the world rushes to trivialize `mild' COVID infection in order to revive economies and get on with life, there remains a great deal we don't know about its long term impact.  A few of many studies suggesting a link to neurological diseases include:

Making matters worse, these risks appear to increase with every infection (see Nature: Acute and Postacute Sequelae Associated with SARS-CoV-2 Reinfection). 

Of course, it isn't just COVID.  

In 2011 a study by Boise State biology professor Troy Rohn  appeared in PLOS ONE , which unexpectedly found immunohistochemical evidence of prior influenza A infection in the post-mortem brain tissues of 12 Parkinson’s patients they tested.

Immunolocalization of Influenza A Virus and Markers of Inflammation in the Human Parkinson's Disease Brain

Troy T. Rohn*, Lindsey W. Catlin

And in 2012, in Revisiting The Influenza-Parkinson’s Link, we looked at another study, conducted by the University of British Columbia, that found a linkage between a past history of severe bouts of influenza and the likelihood of developing Parkinson’s disease later in life.

According to their research, a severe bout of influenza doubled a person’s chances of developing the neurological condition (Severe flu increases risk of Parkinson's: UBC research).

All of which brings us to a new study, published last week in Cell Neuron, which finds statistical linkage between viral illnesses and developing neurodegenerative diseases later in life.  While this falls short of proving causality, it bolsters concerns that their is a genuine link. 

First a link, and some excerpts from the study, followed by an NIH press release.  You'll want to follow the links to read them in their entirety.  I'll have a brief postscript when you return. 


Open Access Published:January 19, 2023 DOI:https://doi.org/10.1016/j.neuron.2022.12.029

Highlights
  • Identified 45 pairs of viral exposures associated with increased risk of NDDs
  • Replicated 22 of the viral exposures/NDD pairings
  • Replicated the previously reported Epstein-Barr and multiple sclerosis association
  • Follow-up shows significantly elevated risk of NDD years after viral exposure
Summary

With recent findings connecting the Epstein-Barr virus to an increased risk of multiple sclerosis and growing concerns regarding the neurological impact of the coronavirus pandemic, we examined potential links between viral exposures and neurodegenerative disease risk.

Using time series data from FinnGen for discovery and cross-sectional data from the UK Biobank for replication, we identified 45 viral exposures significantly associated with increased risk of neurodegenerative disease and replicated 22 of these associations.

The largest effect association was between viral encephalitis exposure and Alzheimer’s disease. I

Influenza with pneumonia was significantly associated with five of the six neurodegenerative diseases studied. We also replicated the Epstein-Barr/multiple sclerosis association. Some of these exposures were associated with an increased risk of neurodegeneration up to 15 years after infection. As vaccines are currently available for some of the associated viruses, vaccination may be a way to reduce some risk of neurodegenerative disease.

          (SNIP)

Finally, in light of the current coronavirus pandemic, our results illustrate the need to take seriously the reports of concomitant neurological symptoms accompanying viral exposures and monitor at risk patients to discover if they will be at higher risk of NDDs in the future.

The findings reported here cover multiple NDDs from two different biobanks, and previous research supports the described associations between viral infection and NDD risk, suggesting that virus/NDD associations are worthy of further investigation.

          (Continue . . . )


For a more generalized summary, you may wish to visit the NIH website to read:



January 19, 2023

NIH biobank study suggests vaccinations against viruses may also reduce risk of neurological disorders

Some viral illnesses may increase a person’s chances of later developing Alzheimer’s disease or another neurodegenerative disorder. Though a causal link cannot be confirmed, an NIH study in which researchers mined the medical records of hundreds of thousands of people in Finland and the United Kingdom found significant associations.

NIH scientists used biobank data to estimate the chances that some viral infections, including influenzas (see picture), may lead to a neurodegenerative disorder diagnosis. 

As published in Neuron, the researchers found there may be at least 22 pairings between a neurodegenerative disorder diagnosis and a previous viral infection that led to a hospital visit. The strongest risk association was between viral encephalitis — an inflammation of the brain caused by a virus — and Alzheimer’s disease.

Meanwhile, hospitalizations due to pneumonia-causing flu viruses were linked to the diagnoses of several disorders, including dementia, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS). The study results also raised the possibility that existing vaccinations may help some people reduce the chances of experiencing these disorders.

          (Continue . . .)


While only a small percentage of people who get COVID, severe flu, or viral encephalitis will go on to develop a neurodegenerative condition later in life, it is an additional risk well worth considering when you are deciding whether to get vaccinated, boosted, or to don a face mask when in a crowd.

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