The rapidity with which coronavirus disease 2019 (COVID-19) has swept across the globe has favored the proliferation of studies usually lacking scientific rigor and the literature on Parkinson’s disease (PD) has not been immune. As a result, studies focusing on the relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19 and PD have provided conflicting results.

Almost two years later, the scientific community is left with the same 6 questions that I sought to answer when I was first invited to talk about this topic during the virtual International Parkinson and Movement Disorders Society. These are the six questions:

1) Are people with PD (PwP) at higher risk for contracting COVID-19 and are there specific contributing factors to that risk?
2) How does COVID-19 affect PD symptoms?
3) How does COVID-19 present in PwP?
4) What are the outcomes in PwP who contract COVID-19?
5) What is the impact of COVID-19 on PD care?
6) Does COVID-19 increase the risk of developing PD?

In spite of the aforementioned issues, the scientific community has little by little provided growing evidence and today we can certainly say that the answers are clearer.

1) Are PwP at higher risk for contracting COVID-19 and are there specific contributing factors to that risk?
It does not appear that PD is a specific risk factor for COVID-19. This is the main finding of the few case-controlled studies, although certain behaviours might have influenced the exposure. For example, some data have indicated that most PwP have strictly followed the guidelines implemented to limit the spread of the pandemic due to the fear of a worse outcome compared to the general population. Partly related to this attitude, many have decided to avoid medical appointments and hospital visits, thus limiting the ability to be properly diagnosed with COVID-19 even if present. Interestingly, studies have indicated a mild but significant protective effect of Vitamin D.

2) How does COVID-19 affect PD symptoms?
There is increasing evidence describing the many direct and indirect (see question 5) negative effects of this pandemic on the motor and non-motor symptoms of PD. Example of direct effects are the worsening of motor control during the acute phase of the viral infection and a slow recovery during the so-called ‘Long Covid’ syndrome.

3) How does COVID-19 present in PwP?
Although many PwP present with typical COVID-19 symptoms, some present atypically with isolated worsening of parkinsonian symptoms, requiring increased anti-PD therapy. In some other cohorts a less prevalent shortness of breath or higher incidence of diarrhea have been reported.

4) What are the outcomes in PwP who contract COVID-19?
Generally speaking, the vast majority of PwP have an excellent outcome, although there’s a trend towards worse outcomes, especially in frail subgroups (e.g. in case of long disease duration and/or advanced age). Mortality data on PwP with COVID-19 has been quite inconclusive (ranging from 5.2% to 100%) but newer data are now available and are overall confirming a poorer outcome compared to non-PD cohorts.

5) What is the impact of COVID-19 on PD care?
More subtle but equally important have been the many and diverse indirect effects of this pandemic: social isolation, poor sleep, increased binge eating, missed medical appointments, lack of rehabilitations, difficulties with receiving advanced care or even simply the right medications are just few examples.

6) Does COVID-19 increase the risk of developing PD?
Single cases of acute hypokinetic-rigid syndrome have been described but no other convincing data has been reported. The critical analysis of these cases seems to suggest that in some cases a true parkinsonism wasn’t present (e.g. in case of encephalitis with reversible akinetic mutism), in other cases parkinsonism wasn’t typical (e.g. it lacked levodopa-responsiveness) and resulted from vascular lesions. The majority of these ‘new-onset’ PD cases were subclinical PD with a faster progression after the infection. Interestingly, a recent pathological study has detected the viral proteins and genomic sequences of SARS-CoV-2 in the brain of a small group of patients who died from COVID-19.

In conclusion, while there’s no convincing reason to be overly worried, a coordinated effort is required to assimilate data and answer these questions in larger PD cohorts. In fact, I am sure that one day these 6 questions will have definite answers.

Alfonso Fasano, MD, PhD, FAAN holds the Chair in Neuromodulation and Multi-Disciplinary Care at the University of Toronto and University Health Network. He is a Professor in the Department of Medicine (Division of Neurology) at the University of Toronto. He is staff neurologist and co-director of the Surgical Program for Movement Disorders at Toronto Western Hospital, University Health Network. He is also a presenter on this subject at WPC 2023. View the Scientific Program here.
Find Alfonso on Twitter: @DrAlfonsoFasano

Ideas and opinions expressed in this post reflect that of the author(s) solely. They do not necessarily reflect the opinions or positions of the World Parkinson Coalition®