Researchers worry SARS-CoV-2 may have long-term neurological impact

Results from a survey of adults both with and without Parkinson’s disease (PD) suggested that the ongoing Covid-19 pandemic has a dramatic impact on motor and non-motor symptoms of PD and led to significant disruptions in care.

“Out of about 5,000 people with PD, about 1% had a definite or probable Covid-19 diagnosis, and 75% of those infected experienced new or worsening PD-related symptoms,” wrote Caroline M. Tanner, MD, PhD, of the Department of Neurology in the Weill Institute for the Neurosciences, University of California San Francisco, and colleagues reported in the Journal of Parkinson’s Disease. “For people with PD without Covid-19, disruptions were frequent in PD-related medical care (64%), essential daily activities (35%), exercise (21%), and social activity (57%), and contributed to worsening of motor and non-motor symptoms especially in specific at-risk groups. Compensatory activities such as telemedicine and online exercise and social programs are important, though these are not available to everyone. As the pandemic and social distancing guidelines will likely last for some time, targeted strategies should be developed to provide support to patients with all levels of resources.”

For their study, Tanner and colleagues invited participants from the online Fox Insight study, with or without PD, to complete a survey from April 23 through May 23, 2020. Patients with missing diagnostic or demographic data and patients who reported a PD diagnosis before age 25 were excluded. Of the 9,762 patients in Fox Insight, 7,209 responded (~74% response rate), 5,429 of whom had PD and 1,452 of whom did not.

The researchers noted that respondents with PD were older, more often male, had a higher prevalence of heart disease, had a lower prevalence of immunocompromising conditions and lung disease, and had lower household income than those without PD.

“Covid-19 diagnoses were reported by 51 people with PD (22 definite, 29 probable) and 26 people without PD (7 definite, 19 probable),” they reported. “Positive tests were reported in 17 people with PD and 6 without PD. One person with PD reported a positive Covid-19 test but was asymptomatic and was not included in analyses of Covid-19-associated disease features.”

Covid-19 and Parkinson’s Disease Symptoms

Tanner and colleagues found that, among the respondents who reported Covid-19 infection, “people with PD reported worsening of many PD-related symptoms. New motor symptoms were reported by 18%, and 55% reported worsening of at least one existing motor symptom. New and worsening non-motor symptoms were reported for all domains: mood (20% new, 51% worsening), cognition (7.8% new, 41% worsening), sleep (12% new, 59% worsening), and autonomic (7.8% new, 29% worsening).”

Patients with PD who develop infectious illnesses often report worsening PD symptoms, the study authors noted, “possibly due to systemic inflammation, altered dopaminergic signaling, or changes in medication absorption or pharmacokinetics. Worsening of symptoms due to a direct infection of the [central nervous system] CNS by SARS-CoV-2 is less likely. Although Covid-19 has been associated with changes on neuroimaging and SARS-CoV-2 RNA has been detected in cerebrospinal fluid, a recent autopsy series of patients that died with Covid-19—all of whom experienced altered mental status—did not find immunohistochemical evidence of encephalitis or viral invasion into brain tissue. Exacerbation of PD symptoms during Covid-19 may in part be due to the inflammatory reaction characteristic of the disease. The consistent reporting of symptom exacerbation in people with PD due to Covid-19 emphasizes the need to consider Covid-19 as a possible explanation for suddenly worsening PD-related symptoms.”

Tanner and colleagues also found that survey respondents with Covid-19, both with and without PD, reported new onset hyposmia, a reduced ability to smell and detect odors—and, PD patients who already had hyposmia reported worsening of this symptom while infected with Covid-19. This symptom was reported at a similar rate to subjective reports in previous studies, they noted.

Disruptions to PD-Related Care

While the vast majority of respondents with PD did not develop Covid-19, 62% reported alterations to healthcare as a result of the pandemic, including cancelled appointments, reduced in-home care, or trouble filling prescriptions. “People with PD not diagnosed with Covid-19 reported disrupted medical care (64%), exercise (21%), and social activities (57%), and worsened motor (43%) and non-motor (52%) symptoms,” Tanner and colleagues reported.

Notably, disruption in medical care was more common among those with longer PD duration (41% PD duration >9 years vs 32% for PD duration 0–3 years, adjusted odds ratio [aOR] = 1.47, 95% CI 1.26–1.73, P< 0.001), the study authors pointed out. Meanwhile, race and low income were both independently associated with difficulty obtaining PD medications (non-White race 13% vs 7.3%, aOR 1.98 95% CI 1.05–3.45, P= 0.023, and lower income 10% vs 7.2%, aOR 1.36, 95% CI 1.07–1.72, P= 0.01), with Latinx patients reporting the largest disruption (14% vs 7.5%, 1.61, 95% CI 0.93–2.63, P= 0.07).

“Telemedicine appointments were reported by 39% of people with PD,” the study authors added, “but those with lower household income were less likely to attend healthcare appointments through telemedicine (40% vs 35%, aOR 0.79, 95% CI 0.69, 0.90, P<0.001).”

Thirty-five percent of respondents with PD reported at least one essential daily activity getting disrupted during the pandemic, they wrote. These disruptions were more commonly reported among patients who lived alone compared to others with PD, including getting food (12% versus 8.7%) and getting home care/housekeeping (15% versus 9%). In addition, 21% and 57% of respondents with PD reported cancelled exercise or social activities, respectively. While many respondents found alternative ways to pursue these activities, such as online classes, PD patients with lower income were less likely to report alternative means of exercising (32% versus 44%) or social activities (49% versus 58%), and older PD patients were less likely to use alternative ways to exercise (39% versus 44%).

The pandemic also hampered patients’ participation in ongoing research — of the 16% of PD patients without Covid-19 who reported participating in research, 40% had to cancel and 35% had to postpone in-person research visits, and 25% were unable to participate in research visits through alternative methods.

These disruptions in care apparently had a substantial impact on patient outcomes, Tanner and colleagues wrote, with patients who experienced interruptions in care more likely to report worsening PD symptoms in all domains (motor symptoms: 56% versus 36%; cognitive problems: 24% versus 4%; mood symptoms: 42% versus 30%; autonomic symptoms: 27% versus 17%; and sleep problems: 42% versus 31% [P for all <0.001]). “New onset motor symptoms in particular were more likely in those that had disruption of medical care (8.2% versus 5.1% aOR 1.63, 95% CI 1.31-2.04, P<0.001),” they noted.

“Respondents who experienced interruptions to exercise, social activities or were asked to self-isolate were also more likely to report worsening of PD symptoms,” Tanner and colleagues added.

The study authors noted that the fact that 35% of people with lower socioeconomic status were able to use telemedicine resources to continue care is encouraging and suggests that this service can be further expanded; however, they also noted that it is vital to minimize the adverse effects of treatment interruptions while continuing to maintain safety precautions. Their study also suggests that patients with longer PD duration and patients living alone need more specific attention, and that existing socioeconomic and racial barriers to healthcare have been further exacerbated by the pandemic, they added.

Parkinsonism: The Third Wave of the Covid-19 Pandemic?

Tanner and colleagues also noted that their study raises important questions for future analyses, including the potential for long-term neurological repercussions for patients who develop SARS-CoV-2 infection.

“Hyposmia predicts PD-associated clinical and pathological changes,” they wrote. “This association, among other neurologic manifestations in people with Covid-19, has prompted worries about the possibility of SARS-CoV-2 infection triggering long-term neurodegeneration, as was observed following the 1917-1918 [Spanish flu] pandemic. This survey will provide useful baseline information for follow-up of respondents with Covid-19, to see if parkinsonism or other neurodegenerative diseases develop in those without PD, or if a different clinical course occurs in those with PD.”

This sentiment echoed concerns raised in a review of reported neurological symptoms associated with Covid-19 infection, published this month in the Journal of Parkinson’s Disease, in which Kevin J. Barnham, PhD, of the Florey Institute of Neuroscience and Mental Health, the University of Melbourne, and the Melbourne Dementia Research Centre in Parkville, Australia, and colleagues warned that parkinsonism may prove to be the “third wave” of the Covid-19 pandemic.

“There may be a myriad of potential long-term neurological and neuropsychiatric complications secondary to SARS-CoV-2 infection including a potential link to worsening parkinsonism in patients with PD and possibly even delayed neurological effects including parkinsonism,” they wrote. “It remains to be seen whether Covid-19 viral infections will be later linked to parkinsonism as is the case in other viruses. Also, unlike many neurological conditions, such as neuropathy, there are emerging tools available to identify parkinsonism early in the disease process. As such, this review serves as a ’call to arms’ for the neurology community in preparation of a potential wave of parkinsonism to come.”

Barnham and colleagues pointed to several systematic reviews and case reports that reported neurological symptoms in patients with Covid-19, including acute cerebrovascular disease, dizziness, headache, hypogeusia, impaired consciousness, Guillain-Barre syndrome, neuralgia, epilepsy, ataxia, encephalitis, and hyposmia. However, they also acknowledged that “there is insufficient data at this stage to quantify the increased risk of developing parkinsonism associated with Covid-19.”

Nonetheless, they encouraged researchers to undertake population-based studies of the neurological symptoms of SARS-CoV-2 infection, and they called for “substantial investment in the early identification, diagnosis, and treatment of PD and parkinsonism to help arm clinicians with the best tools available to handle a potential influx of parkinsonism over the next half-century.”

For their own study, Tanner and colleagues noted several limitations, including a modest response rate, reliance on self-reporting, an inability to capture Covid-19 cases that resulted in death, and underrepresentation among certain populations. However, they argued that this survey provides a useful opportunity to evaluate the long-term effects of Covid-19 on PD progression and the social and public health impacts of the pandemic on this patient population.

“The Covid-19 pandemic will likely have long-term repercussions; intervention to mitigate those effects in our patients should begin as soon as possible,” they added.

  1. Parkinson’s disease patients who were infected with SARS-CoV-2 reported new or worsening PD-symptoms over the course of their infection, researchers reported.
  2. Even patients with Parkinson’s disease who did not develop Covid-19 were impacted by the pandemic in the form of major disruptions to PD-related healthcare and worsening of both motor and non-motor symptoms.

John McKenna, Associate Editor, BreakingMED™

Tanner reported grants from Parkinson Foundation, Gateway LLC, Roche/Genentech, Parkinson Study Group, Michael J. Fox Foundation, NIH/NIA, NIH/NINDS, VA Merit, Dept of Defense, Biogen Idec, Roche Genentech and personal feed from Biogen Idec, Acorda, Adamas Therapeutics, Amneal, CNS Ratings, Grey Matter LLC, Northwestern University, Partnets, Harvard, Guidemark Health, Acadia, Neurocrine, Lundbeck, and Cadent.

Barnham and colleagues had no conflicts of interest to disclose.

 

Cat ID: 125

Topic ID: 79,125,730,933,125,190,926,37,192,927,151,928,925,934