Update on COVID-19 and Parkinson’s disease

Latest Research on COVID-19 & Parkinson’s disease

UPDATE: This post (originally published in June) has been updated with the latest information available.
We will continue to keep this post up-to-date as new information develops.

As citizens of the world, we all continue to grapple with the COVID-19 pandemic. And as members of the Parkinson’s disease (PD) community, we continue to have specific concerns about COVID-19 and how it relates to PD. There is so much information out there, some of it misinformation, so it is important to rely on credible, trusted sources. In this post, I will cover the latest information (as of the date this was published) that investigates the relationship between PD and COVID-19.

What the research data tells us

Over the past eight months, physicians and scientists with expertise in PD have gathered their preliminary data on the experience of people with PD with COVID-19. These findings have been published in journals for others to learn from. This type of work is not unique to PD of course. Physicians are collating the data on how COVID-19 affects different people with the entire array of human conditions.

The data falls into two general categories:

• Data regarding the lived experience of people with PD during the era of the pandemic COVID-19 (meaning the effect of the COVID-19 situation at large on their lives, not the effects of having contracted the virus)
• Data regarding people with PD who have contracted COVID-19

Studies that investigate the relationship between PD and COVID-19

1. A study of anxiety during the pandemic was conducted in Iran. Patients with PD were asked to fill out questionnaires to rate their levels of anxiety. Questionnaires also contained questions related to PD and COVID-19. Data was collected from patients, caregivers and controls. The study showed that:
   • Levels of moderate and severe anxiety were significantly increased in PD patients over caregivers or controls.
   • 20% of patients that were polled felt that the COVID-19 pandemic exacerbated their PD symptoms.
   • 12% increased their PD medication use during the pandemic.
2. A study of the impact of the COVID-19 lockdown on PD patients was conducted in Egypt. Patients from the movement disorders clinic were assessed over the phone. The study demonstrated that:
   • Compared to controls, PD patients had significantly increased levels of stress, depression and anxiety along with decreased measures of quality of life, as compared to controls.
   • PD patients also reported a significant decline in physical activity as compared to pre-lockdown.
3. Two movement disorders groups – one in London and one in Italy – published a case series of 10 patients with advanced PD symptoms and COVID-19. The average age of the group was 78 with a 12-year duration of disease. The study showed that:
   • Most of the group that was studied required additional levodopa during their COVID-19 infection.
   • Anxiety, fatigue, orthostatic hypotension, cognitive impairment, and psychosis worsened during the infection.
   • Four patients (40%) died.
   • The case series was not large enough to statistically determine if risk of death is increased in people with advanced PD over other patients of the same age.
4. Another study took a different approach and did not report on the known cases of people with PD and COVID-19 (which would skew the people studied to ones who were sicker and thereby came to the attention of their movement disorders physicians). Instead, they selected a non-biased sample of people with PD in Northern Italy and interviewed them to determine their experience with COVID-19. Of the group of PD patients that were randomly selected for interview, 8.5% were found to have contracted COVID-19.

An analysis of this group of people with PD and COVID-19 showed that:

• • They were statistically of a similar age (approximately 66) and had a similar disease duration (approximately 8 years) as compared to those with PD that did not contract COVID-19.
  • Most has mild COVID-19 illness.
  • One needed to be hospitalized.
  • No one died.
  • The number of patients with PD and COVID-19 who were interviewed was small which limits the ability to draw statistically meaningful conclusions. However, hospitalizations and deaths for this group were similar to those with COVID-19 in Northern Italy who did not have PD. While ill with COVID-19 however, there was worsening of both motor and non-motor PD symptoms, which required changes in medication in one third of cases. The most significant non-motor issues were urinary problems and fatigue.

5. A case series was published which detailed the cases of two patients with advanced PD whose PD symptoms suddenly worsened right before a diagnosis of COVID-19 infection. The symptom worsening included increased falls, increased speech disturbances, and increased swallowing difficulties.

This study confirmed a well-known reality, that sudden worsening of PD can indicate that an inter-current medical illness is brewing.  In the past, urinary tract infection was often considered first, but today, COVID-19 must be strongly considered among the possible illnesses that could be responsible for the worsening of PD symptoms.

6. In one study, 740 people with PD were interviewed about their COVID-19 experience. Only seven people among this cohort had contracted COVID-19, with one reported death. Among those with PD who did not contract COVID-19, about 30% reported a worsening of motor symptoms, mood, anxiety or insomnia during the period of lockdown.
7. In a similar but larger study, 2,238 patients at multiple PD centers in Italy were interviewed about their COVID-19 experience. 117 of the patients reported COVID-19 infection. A total mortality rate of 20% was reported in this group, with increased mortality correlating with advanced age, hypertension, dementia and more advanced PD (meaning longer duration of disease and higher levodopa requirements).

This study confirmed that mortality of patient with PD with COVID-19 tracks with increased frailty, comorbidities, and advanced age. The correlate of this conclusion is that those with PD who are generally fit, may not experience COVID-19 outcomes that are very different from others of their own age and with similar comorbidity profiles.

8. In order to further clarify whether having PD was a risk factor for increased mortality in COVID-19, one study analyzed a database of approximately 80,000 people with COVID-19, of which approximately 700 were diagnosed with PD. The study showed that the death rate from COVID-19 of those without PD was 5.5%, and was 21.3% for those with However, these results had to be adjusted statistically because the group with PD were also significantly older than the group without PD and it is well known that age alone causes a dramatic increase in death rates from COVID-19. Even with adjustment for age however, the risk of dying from COVID-19 with PD was slightly elevated over those without PD.
9. In one study the data of over 5,000 people with PD and close to 1,500 people without PD were analyzed (with COVID-19 diagnoses reported by 51 people with and 26 without PD). The majority of people with PD who were infected with COVID-19 reported new or worsening motor and/or non-motor PD symptoms. Those with PD without COVID-19 also experienced worsening of motor and non-motor PD symptoms.  People with PD without COVID-19 were affected in various ways from COVID-19 restrictions including disruptions in their medical care, exercise routines and other social activities.

To summarize, although these different studies report varying statistics, the basic principles are:

• Mortality due to COVID-19 among people with PD correlates with more advanced disease.
• Motor and non-motor symptoms increased during the COVID-19 lockdowns in people with PD who did not contract COVID-19.
• People with PD who contracted COVID-19 often reported new or worsening motor and/or non-motor symptoms in the setting of their illness.

Another issue that has emerged in the literature is:

Does COVID-19 invade the central nervous system? If so, can it contribute to development of PD?

Without a doubt, SARS-CoV2, the virus that causes COVID-19, does most of its damage by invading the respiratory system. However, the consequences of the virus can be seen elsewhere in the body as well, with symptoms including diarrhea and rash. There has been debate as to whether SARS-CoV2 can enter the nerves of the brain or spinal cord and there have been studies published in the literature trying to understand this issue. It is known that SARS-CoV2 enters cells through the angiotensin converting enzyme 2 (ACE2) receptor and there is no clear evidence yet that this receptor is found in brain cells. However, it is possible that the receptor is expressed in the brain under specific circumstances, such as inflammation in the brain. It is also possible that additional methods of entry into the brain occur.

Two main types of evidence that SARS-CoV2 affects the brain are reported:

• Studies on neurological symptoms of those with COVID-19.
  1. Studies looked at all neurologic symptoms in patients with COVID-19 and reported on how common they are (approximately 30%). However, this type of study can be tricky to interpret as they mostly include general neurologic symptoms such as headache and dizziness. These symptoms are likely not due to direct invasion of the virus into the brain, but rather reflect a general state of medical illness.
  2. Strokes can be seen uncommonly in acutely ill COVID-19 patients and this symptom is also likely not due to direct invasion of the nerves, but rather reflects a tendency for blood to abnormally clot, which is reported in severe COVID-19 infections.
  3. Some studies focused on the rarer neurologic complications seen in COVID-19. In this category are neuro-inflammatory syndromes such as encephalitis, acute inflammation of the brain which can cause impaired consciousness, seizures, and abnormal movements. Even in the patients with encephalitis however, the virus could not routinely be isolated from the cerebral spinal fluid (CSF) and these syndromes may therefore reflect a general state of inflammation caused by COVID-19 and not a direct infection of the brain.
• Studies which have attempted to isolate the virus from either the cerebrospinal fluid or the brain itself. Another set of studies have tried to find the virus in CSF or brain tissue of people infected with the virus. In one study, 36% of brains from 27 people who died from COVID-19 demonstrated low levels of SARS-CoV2 RNA in the brain. There are also rare reports of SARS-CoV2 presence in the CSF.

Can COVID-19 cause PD?

There have been some articles in the medical literature which have been covered in the general media, suggesting that COVID-19 is linked to PD. It must be emphasized however, that COVID-19 is such a new illness, and PD is known to be a disease that develops slowly over years, that any suggestion that COVID-19 causes PD can only be speculation about what may happen in the future. This review article nicely explains all the issues to consider when thinking about the relationship between SARS-CoV2 and PD.

There are a few lines of evidence that have been suggested that connect SARS-CoV2 to PD:

• SARS-CoV2 can cause loss of smell – this is a well-described symptom of COVID-19 which is not typically seen in other respiratory viruses. Most people who experience loss of smell associated with COVID-19 regain their sense of smell after recovery. There are reports however, of those whose recovery of their smell is very delayed or incomplete. And we know that loss of smell can also occur early in the course of PD. However, we do not know whether lack of smell in COVID-19 shares the same mechanism by which loss of smell occurs in PD. It remains unclear therefore, whether the COVID-19 and PD are related or merely share a symptom.
• There are three case reports in the literature, one of a 45 year old man who developed acute onset parkinsonism in the setting of COVID-19, one of a 35 year old woman who developed parkinsonism after mild COVID-19 infection, and one of a 58 year old man who developed a more complicated parkinsonian syndrome, which subsequently improved, in the setting of COVID-19. In context however, this means that many millions of people contracted the virus without developing these complications.
• The Spanish flu, which caused millions of deaths around the world between the years 1918-1920, and to which the current pandemic has been compared, has been linked to an acute brain inflammation called encephalitis lethargica, which appeared in the world from 1917-1928 and then disappeared. In some cases, post-infectious parkinsonism developed in the aftermath of encephalitis lethargica, up to a year after the infection. (It should be noted that it was never confirmed that the Spanish flu caused encephalitis lethargica.) People with this post-infectious parkinsonism were chronicled by the famous neurologist Dr. Oliver Sacks in his book Awakenings (which became the source of the movie Awakenings). Although the Spanish flu was caused by an entirely different virus from SARS-CoV2 (indeed, it was not a coronavirus), it does stand as an example of a primarily respiratory infection associated with delayed parkinsonism as a neurological consequence.

In summary, although there are some intriguing connections between SARS-CoV2 are PD, there is no concrete evidence that this virus will contribute to PD risk in the future.

Tips and Takeaways

• It is important to consult credible sources of information about COVID-19. APDA has summarized the latest scientific data and reports to help you better understand the connection between COVID-19 and PD.
• People with PD demonstrated more anxiety and depression as well as decreased levels of quality of life and physical activity as compared to controls during the COVID-19 lockdown.
• A random sampling of a small group of mid-stage PD patients with COVID-19 demonstrated outcomes that were similar to others of the same age with COVID-19 who did not have PD.
• In advanced PD, a rapid worsening of PD could mean onset of COVID-19 infection.
• Mortality due to COVID-19 among people with PD correlates with more advanced disease.
• Neurologic symptoms can occur with COVID-19 infections, but the majority are due to general illness and not specific involvement of the brain in the illness.
• There is speculation in the literature and general media that COVID-19 will contribute to increased PD risk. However, the virus is too new for there to be concrete evidence to support this claim.