PARKINSON’S DISEASE/PARKINSONISM AS A RESULT OF COVID-19? · Parkinson's Resource Organization

PARKINSON’S DISEASE/PARKINSONISM AS A RESULT OF COVID-19?

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UPDATE ON THE ROAD TO THE CURE

A REAL-TIME SCIENCE REPORT

by Ram Bhatt, Ph.D., CEO, CSO of ICBII

Since December 2019, the world has been caught off guard by COVID-19, a disease caused by the disastrous Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). As of September 26, 2020, more than 32,400,000 cases of COVID-19 have been reported globally with 985,823 deaths. The US alone has 6,910,082 COVID-19 cases with more than 201,634 deaths. 

ASSOCIATION OF NEUROLOGICAL SYMPTOMS WITH COVID-19

To date, there have been at least three major case reports demonstrating the presence of neurological symptoms in COVID-19. For example, Mao et al. performed a retrospective case study on 214 hospitalized patients in China and demonstrated that 78 (36.4%) patients presented with varying neurological symptoms for instance: headache, dizziness, hyposmia, and skeletal muscle symptoms [JAMA, Neurology, 77, 683 (2019)]. Helms et al. evaluated 58 hospitalized patients in France, 8 (13.8%) had neurological symptoms upon admission into the intensive care unit (ICU), and a further 39 (67.2%) demonstrated neurological symptoms when sedation and neuromuscular blockers were withheld [New Eng. Jour. Med., 382, 2268 (2020)]. Romero-Sanchez analyzed the medical history of patients on the Spanish ALBACOVID registry [Neurology, 95, e1060 (2020)]. Of the 841 patients in this study, 483 (57.4%) developed neurological symptoms and of the 197 people who died, neurological complications were determined to be the cause of death in 8 (4.1%). The neurological symptoms reported to date, range from severe, such as encephalitis (brain inflammation) in hospitalized patients to mild (e.g., hyposmia). 

Even though there were no control groups associated with these reports, which would have been of great value to understand the prevalence of these neurological symptoms in COVID-19, there is evidence that SARS-CoV-2 can affect the central nervous system (CNS).  This is reflected in the large number of COVID-19 patients presenting with concurrent olfactory complications. As of today, six studies have been performed that utilize clinical olfactory tests, including the Sniffin’ Sticks, University of Pennsylvania Smell Identification Test (UPSIT), and Connecticut Chemosensory Clinical Research Centre Test (CCCRC), that can quantify the degree of hyposmia and anosmia in patients.  These data demonstrate a range of olfactory disruption prevalence from 58.3–87.1%, which is substantially higher than originally reported. 

SARS-CoV-2 Entry into the CNS

How does a giant viral particle such as that of SARS-CoV-2 enter the CNS when most even small molecule drugs cannot cross the blood-brain barrier?  Several viruses are known to be neurotropic (invading of nerve cells), including herpes simplex virus, poliovirus, influenza Type A virus, Swine Flu (H1N1), Avian Flu (H5N1), and the coronaviruses. To understand the pathogenesis of these viruses within the central nervous system, it is critical to understand the mechanisms of entry into the CNS. There are many ways in which viruses are hypothesized to enter the brain:

  1.  Infection of the Olfactory Epithelium: The virus that has been studied the most, with a view to understanding CNS penetration and the subsequent neurotropism, is influenza. It has been reported that intranasal infection with H1N1 (Swine Flu) and H5N1 (Avian Flu) resulted in infection of the olfactory epithelium and transmission through the axons into the olfactory bulb of wildtype mice.
    SARS-CoV-2 may be using the route for CNS penetration. 
     
  2. Viremia: Viruses with RNA genome such as SARS-CoV-2 has an outer protein core that is stabilized by the lipids. It is a well-known fact that lipids facilitate blood-brain barrier permeability. Since the virus is detectable in the blood it is highly probable that lipid layer on viral particles circulating in the blood help transport SARS-CoV-2 into the brain.
Can COVID-19 Result in Parkinson’s/Parkinsonism?

Since loss of smell is one of the symptoms of Parkinson’s disease/parkinsonism and there is a convincing evidence that COVID-19 patients experienced anosmia, there is a potential of myriad of long-term delayed neurological and neuropsychiatric complications secondary to SARS-CoV-2 infection including a potential link to worsening parkinsonism in Parkinson’s patients. However, there is insufficient data at this point to quantify the increased risk of developing parkinsonism associated with COVID-19. The high prevalence of anosmia combined with a suspicion about a link between an encephalitis lethargica-type association with a historic influenza pandemic leads us to question whether history is going to repeat again. At face value it is attractive to equate the hyposmia and anosmia in COVID-19 to the hyposmia and anosmia in parkinsonism. Such a determination cannot be unequivocally made without extensive future studies on patients recovered from the disease. One can only postulate today that there may be an increase in the risk profile of individuals with neurological complications associated with SARS-CoV-2 infection, as demonstrated by symptoms such as hyposmia or encephalitis that may reflect a neurological injury. Furthermore, individuals who have more severe symptoms may have a higher risk of developing parkinsonism. 

The best cure for the potential future epidemic of neurological disorders due to delayed affect of COVID-19 is in our hands right now and that is the prevention of SARS-CoV-2 infection by using common sense methods to mitigate the chances of infection.

Would you like to help get ICBII’s drugs to market faster?

The joy of being a part of this historical event can be had by helping ICBI find the funds to bring these trials to fruition through your investing, and by finding others with the financial ability and humanitarian mindset to accomplish the—until now—impossible. Please contact ICBI directly through their website icbii.com, or by phone at 858-455-9880, or contact Jo Rosen at PRO for a personal introduction to the scientists.

IMAGINE the world without Parkinson’s, MSA, or Alzheimer’s disease. JUST IMAGINE.

 

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Updated: August 16, 2017