There's no robust evidence that having Parkinson's disease increases susceptibility to COVID-19, or that COVID-19 confers a greater risk of Parkinson's disease.
But there are reported cases of worsening Parkinson's symptoms in infected patients, said K. Ray Chaudhuri, MD, DSc, of King's College London in England. A community-based , for example, suggested substantial symptom worsening in Parkinson's patients with mild-to-moderate COVID-19, independent of age and disease duration.
also have shown that most people with Parkinson's disease and COVID-19 experience new or worsening motor and non-motor symptoms. The survey findings, published in the Journal of Parkinson's Disease, were the first and largest self-reported data set to date about Parkinson's disease symptoms and care disruptions during the pandemic.
"This is quite useful because it gives us insight into the patient's own experience," said Caroline Tanner, MD, PhD, of the University of California San Francisco, who led the study.
"Pretty much everyone had a worsening of Parkinson's symptoms if they were also infected with COVID-19," Tanner said. "It's relevant for us to have this in mind, so it's part of what we're thinking when we hear patients talk about sudden worsening."
The online survey, conducted by the Michael J. Fox Foundation for Parkinson's Research in April and May, included 5,429 Parkinson's disease patients and 1,452 people without Parkinson's. Of these, 77 people reported a COVID-19 diagnosis, including 51 Parkinson's patients.
During SARS-CoV-2 infection, most Parkinson's patients experienced new or worsening motor symptoms (63%) and non-motor (75%) symptoms, including stiffness, tremor, difficulty walking, mood symptoms, cognition, and fatigue.
Among all respondents with COVID-19, outcomes were largely similar between people with and without Parkinson's. Longer Parkinson's disease duration was associated with a higher risk of pneumonia, the need for supplemental oxygen, or hospitalization (44% for disease duration greater than 9 years vs 14% for disease duration of 9 years or less).
"What was really remarkable was the number of people who didn't have COVID, but who did suffer from the experience of the pandemic," Tanner noted. Medical care (64%), exercise (21%), and social activities (57%) were disrupted for these patients, and many reported worse Parkinson's motor (43%) and non-motor (52%) symptoms.
New-onset motor symptoms were more likely in Parkinson's patients who had disrupted medical care. Patients who experienced interruptions to exercise, social activities, or who were asked to self-isolate also were more likely to report worsening of Parkinson's symptoms.
To date, there's no data from large-scale observational studies about people with Parkinson's disease who have COVID, but it seems younger patients at early motor stages without significant comorbidities may not have high risk for adverse outcomes, Chaudhuri noted.
Frail, older Parkinson's patients with advanced motor disease, comorbidities, or who are undertaking advanced therapies may have more complications. "Frailty in Parkinson's is a risk factor," Chaudhuri said. "Such patients must have their vitamin D checked. Management should focus on fatigue and pain, as well as possible increased levodopa requirement."
Is Post-COVID Parkinsonism Possible?
More than 6 months into the COVID-19 pandemic, one thing still isn't clear: what SARS-CoV-2 can do to the brain. There are theories, and olfactory dysfunction has been well documented, but pathology studies haven't really answered the key question of whether the virus enters central nervous system neurons, astrocytes, or microglia, noted Chaudhuri.
A recent case report in showed that a 45-year-old Israeli patient was diagnosed with probable Parkinson's disease several months after he was hospitalized with SARS-CoV-2 infection, though the mechanism that led to this was unclear.
Viral infections and parkinsonism have been linked together before, most notably the post-encephalitic parkinsonism seen during an unusual outbreak of , or "sleeping sickness," that coincided with the 1918 Spanish flu.
No causal evidence ties encephalitis lethargica -- the subject of the -- to the Spanish flu. In COVID-19, reports of encephalopathy have been slow to emerge, and so far, there's been only a single case report of parkinsonism.
While SARS-CoV-2 has infected millions of people, "there are only a , and only two that show evidence of COVID-19 virus in the cerebrospinal fluid as assessed by reverse transcription polymerase chain reaction (RT-PCR)," Chaudhuri and colleagues wrote in npj Parkinson's Disease.
"This suggests that even with the presence of high viral load in the blood stream and severe inflammation, COVID-19 virus is unlikely to exhibit direct neurotropism, but rather appears to cause inflammatory-mediated brain responses," they added.
The idea that a peripheral cytokine storm from non-neurotropic viruses can induce encephalitis has been suggested for other viral infections, including the 1918 flu and respiratory syncytial virus, Chaudhuri and co-authors noted.
Some scientists have wondered if COVID-19 survivors may represent a large proportion of the future Parkinson's patient population. Evidence about the Spanish flu is inconclusive, but people who were born or were young at the time of the 1918 influenza outbreak had a two- to threefold than people born before 1888 or after 1924, noted Carla Alessandra Scorza, PhD, of the Federal University of São Paulo in Brazil, and co-authors in the Journal of Parkinson's Disease.
"The long-term link between viruses and neurodegenerative disorders is difficult to demonstrate, but we should not cast aside the long-lasting impacts that the growing COVID-19 pandemic may have on the pandemic of Parkinson's disease," they wrote.
"Although it is too early to know what the long-term consequences of COVID-19 will be on the brain, clinical psychiatry and neurology research communities need to be vigilant in monitoring how those who recover from moderate and severe COVID-19 fare in the future," said Patrik Brundin, MD, PhD, director of the Center for Neurodegenerative Science at the Van Andel Institute in Grand Rapids, Michigan.
"Depressive disorders are undoubtedly associated with inflammation, and there is mounting evidence that both inflammation and infections are associated with elevated risk for Parkinson's disease later in life," he pointed out.
Animal studies also indicate that other RNA viruses are linked to marked elevations in alpha-synuclein in the brain, Brundin noted, "adding further concern about what the long-term effects of SARS-CoV-2 might be."