#19,319
One of the great - yet unanswered - questions about acute viral illnesses is what role (if any) do they play in the development of neurodegenerative diseases, perhaps years or even decades later?
A hundred years ago the world was embroiled in a global epidemic of Encephalitis Lethargica (EL) following the 1918 influenza pandemic, which appears to have affected millions of people.
While a viral cause is suspected, it isn't clear whether it was sequelae from the H1N1 influenza virus, or from some other viral agent (see Evidence for an enterovirus as the cause of encephalitis lethargica).
Throughout history, there have been other reports of neurological outbreaks following severe epidemics, including febris comatosa which sparked a severe outbreak in London between 1673 and 1675, and following the 1889–1890 influenza (?) pandemic, a severe wave of somnolent illnesses (nicknamed the "Nona") was described in Italy
Among those who survived, Parkinsonism and other neurological sequelae was common.
Over the past 6 years, we've seen numerous reports of memory and neurological problems associated with COVID infection, including 2025's BMC Neurology: Long-term Neurological and Cognitive Impact of COVID-19: A Systematic Review and Meta-analysis in over 4 Million Patients.
While this is an extensive review - and its 16-page PDF deserves careful review - briefly, they report fatigue affecting over 40% of patients and memory disorders affecting nearly 30%, at least 6 months post infection.
More broadly, in 2023 we looked at a study (see Neuron: Virus Exposure and Neurodegenerative Disease Risk Across National Biobanks), which found statistical linkage between viral illnesses and developing neurodegenerative diseases in the future.
With the very strong caveat that the exact cause of Alzheimer's, Parkinson's, and other neurodegenerative diseases are not yet known - and all are likely the result of multiple genetic and environmental factors - the role of infectious diseases is a hypothesis under serious investigation.
All of which brings us to a report in Nature Communications which reports that a single, nonfatal respiratory virus infection appears to hasten ALS-like disease in genetically susceptible mice (SOD1-G93A mutation).
ALS-susceptible mice were infected before they showed motor symptoms with either influenza A (H1N1) or SARS-CoV-2 and compared with uninfected (SOD1-G93A) mice.
- Influenza-infected mice developed declining motor performance earlier and reached severe ALS-related endpoints sooner.
- SARS-CoV-2 infected mice saw similar declines in motor ability, but their endpoint was not significantly shortened.
Acute viral infection accelerates neurodegeneration in a mouse model of ALSArt Marzok, Jonathan P. Mapletoft, Imran Ahmed, Braeden Cowbrough, Daniel B. Celeste, Michael R. D’Agostino, Jann C. Ang, Andrew T. Chen, Vithushan Surendran, Yona Tugg, Hahn Li, Karena Wong, Anna Dvorkin-Gheva, Ali Zhang,
Hannah D. Stacey, Mannie Lam, Yasmine Kollar, Kevin R. Milnes, Sam Afkhami & Matthew S. Miller
Nature Communications (2026) Cite this article
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Abstract
While several viral infections have been associated with amyotrophic lateral sclerosis (ALS), the mechanism(s) through which they promote disease remains elusive. Here we investigate the impact of common, acute viral infections on ALS disease onset and progression in the SOD1G93A mouse model.A single sublethal infection prior to onset of ALS clinical signs is associated with markedly accelerated ALS disease progression characterized by rapid loss of hindlimb function. Prior infection results in gliosis in the lumbar spine and upregulation of transcriptional pathways involved in inflammatory responses, metabolic dysregulation, and muscular dysfunction. Therapeutic suppression of gliosis with an anti-inflammatory small molecule, or administration of a direct-acting antiviral, is associated with significantly improved ALS clinical signs, akin to what is observed in uninfected animals.Our study provides causal and mechanistic evidence that the immune response elicited by acute viral infections may be an important etiological factor that alters ALS disease trajectory.
Although the link between COVID/Flu infection and neurodegenerative diseases later in life is far from established, over the past 15 years we've seen numerous studies that have linked heart attacks and strokes to acute influenza and respiratory infections.
At the same time, we've seen growing evidence that the uptake of the seasonal flu vaccine may reduce the incidence of heart attack and stroke, even if the vaccine doesn't prevent influenza infection.
Conclusions
Our findings add to the evidence that influenza vaccination confers cardiovascular protection. In this study, prior vaccination halved the excess risk of acute myocardial infarction or stroke following breakthrough influenza infection.
Which is why I'll be rolling up my sleeve again for my 21st consecutive yearly flu shot later this month, and why I'll be getting the updated COVID shot when it becomes available.
If they turn out to be neuroprotective as well, I'll consider it a welcome bonus.
