Wednesday, September 23, 2020

Review Article: Parkinsonism as a Third Wave of the COVID-19 Pandemic?



Within the first few months of COVID-19's arrival it became apparent that the SARS-CoV-2 virus was producing a high morbidity - low mortality pandemic; several times deadlier than than seasonal flu, but not as lethal as would be expected from MERS-CoV, SARS, or avian H5N1, H5N6, or H7N9.

Hospitalized patients often required weeks of medical care before being discharged, and a significant number of `recovered' patients continue to battle lingering - and sometimes permanent - health issues.

We've seen ample evidence that the SARS-CoV-2 virus provokes far more than just a respiratory disease (see Nature Med. Review: Extrapulmonary manifestations of COVID-19), and reports of cardiac, renal, pulmonary, and neurological impacts are increasingly common. 

Eurosurveillance: Reduced Maximal Aerobic Capacity After COVID-19 In Young Adult Recruits

JASN: Acute Kidney Injury In Hospitalized Patients With COVID-19

JAMA: Two Studies Linking SARS-CoV-2 Infection To Cardiac Injury

The Lancet: Yet Another Study On Neurological Manifestations In Severe COVID-19 Patients

In early July, Dr. Anthony Fauci expressed concerns that many COVID patients are suffering from a post-viral syndrome - similar to ME/CFS - which has disabled and traumatized well over a million Americans over the past 3 decades (see NIH About CFS/ME).

The long-term public health legacy of this pandemic is uncertain, but over the past few months we've seen cardiologists and neurologists weigh in on the potential for seeing huge increases in COVID-19 related heart failure and neurological diseases, some that may not become fully apparent for years.
Clyde W. Yancy, MD, MSc1,2; Gregg C. Fonarow, MD3,4
JAMA Cardiol. Published online July 27, 2020. doi:10.1001/jamacardio.2020.3575

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

In the decade following the 1918 pandemic, the world saw a huge increase in Parkinsonism and other neurological conditions, including Encephalitis Lethargica (see  The Lancet: COVID-19: Can We Learn From Encephalitis Lethargica?).

Although a causal link to the 1918 H1N1 pandemic virus has not been established, many researchers believe these neurological epidemics of the 1920s were caused by either a viral infection or the body's immune response to an infection (see Nature Comms: Revisiting The Influenza-Parkinson's Link).

While there are relatively simple medical tests to detect diminished cardiac, lung, or renal function, the same can not be said for pre-clinical Parkinsonism (a group specific neurological disorders, which includes Parkinson's Disease). 

It may take years before we can fully appreciate COVID's ultimate impact on neurological health. 

All of which brings us to a Review Article, published yesterday in the Journal of Parkinson's Disease, that looks at the parallels between COVID-19 and epidemics of the past, and the potential for seeing a new wave of neurological disorders. 

This is a lengthy, and quite detailed review. I've only posted the link and a brief excerpt from the abstract, you'll want to follow the link to read it in its entirety.  I've also included a link, and some excerpts, from a press release.  

Parkinsonism as a Third Wave of the COVID-19 Pandemic?
Authors: Beauchamp, Leah C.a; b | Finkelstein, David I.a | Bush, Ashley I.a; c | Evans, Andrew H.d | Barnham, Kevin J.a; b; c; *
Correspondence: [*] Correspondence to: Kevin J. Barnham, PhD, Florey Institute of Neuroscience and Mental Health, Parkville, Australia. E-mail:
Keywords: Parkinson’s disease, parkinsonism, COVID-19, SARS-CoV-2
DOI: 10.3233/JPD-202211
Journal: Journal of Parkinson's Disease, vol. Pre-press, no. Pre-press, pp. 1-11, 2020
Accepted 27 August 2020 | Published: 22 September 2020

Since the initial reports of COVID-19 in December 2019, the world has been gripped by the disastrous acute respiratory disease caused by the SARS-CoV-2 virus. There are an ever-increasing number of reports of neurological symptoms in patients, from severe (encephalitis), to mild (hyposmia), suggesting the potential for neurotropism of SARS-CoV-2.
This Perspective investigates the hypothesis that the reliance on self-reporting of hyposmia has resulted in an underestimation of neurological symptoms in COVID-19 patients. While the acute effect of the virus on the nervous system function is vastly overshadowed by the respiratory effects, we propose that it will be important to monitor convalescent individuals for potential long-term implications that may include neurodegenerative sequelae such as viral-associated parkinsonism.

 As it is possible to identify premorbid harbingers of Parkinson’s disease, we propose long-term screening of SARS-CoV-2 cases post-recovery for these expressions of neurodegenerative disease. 

An accurate understanding of the incidence of neurological complications in COVID-19 requires long-term monitoring for sequelae after remission and a strategized health policy to ensure healthcare systems all over the world are prepared for a third wave of the virus in the form of parkinsonism.
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MELBOURNE, Australia, September 22, 2020 - Is the world prepared a wave of neurological consequences that may be on its way as a result of COVID-19? This question is at the forefront of research underway at the Florey Institute of Neuroscience and Mental Health. A team of neuroscientists and clinicians are examining the potential link between COVID-19 and increased risk of Parkinson's disease, and measures to get ahead of the curve.

"Although scientists are still learning how the SARS-CoV-2 virus is able to invade the brain and central nervous system, the fact that it's getting in there is clear. Our best understanding is that the virus can cause insult to brain cells, with potential for neurodegeneration to follow on from there," said Professor Kevin Barnham from the Florey Institute of Neuroscience & Mental Health.

In a review paper published today, researchers put spotlight on the potential long-term neurological consequences of COVID-19, dubbing it the 'silent wave'. They are calling for urgent action to be taken to have available more accurate diagnostic tools to identify neurodegeneration early on and a long-term monitoring approach for people who have been infected with the SARS-CoV-2 virus.

The researchers report that neurological symptoms in people infected with the virus have ranged from severe, such as brain hypoxia (lack of oxygen), to more common symptoms such as loss of smell.

"We found that loss of smell or reduced smell was on average reported in three out of four people infected with the SARS-CoV-2 virus. While on the surface this symptom can appear as little cause for concern, it actually tells us a lot about what's happening on the inside and that is that there's acute inflammation in the olfactory system responsible for smell," explained Florey researcher Leah Beauchamp.

Inflammation is understood to play a major role in the pathogenesis of neurogenerative disease and has been particularly well studied in Parkinson's. Further research into these illnesses may prove critical for future impacts of SARS-CoV-2.

"We believe that loss of smell presents a new way forward in detecting someone's risk of developing Parkinson's disease early. Armed with the knowledge that loss of smell presents in around 90% of people in the early stages of Parkinson's disease and a decade ahead of motor symptoms, we feel we are on the right track," added Ms Beauchamp.

Clinical diagnosis of Parkinson's disease currently relies on presentation of motor dysfunction, but research shows that by this time 50-70% of dopamine cell loss in the brain has already occurred. 


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The popular notion is that if you are young and healthy, COVID-19 is likely to be a minor illness with little or no lasting sequelae. And for many - perhaps even most - that is likely true. But the evidence suggests not everyone who contracts the virus - and recovers - will come away unscathed.

Like Agent Orange, or the air quality at ground zero in Manhattan, the risks from COVID-19 many not become fully apparent for years.

Something to seriously consider when deciding how rigorously to follow social distancing and other NPI recommendations this fall and winter.