4. Discussion
The increased susceptibility to COVID-19 in patients with Parkinson disease and other movement disorders has been presumed and was a source of heightened concern in the early months of this pandemic [5,6,10]. The inherent characteristics and comorbidities of this population made it quite plausible that these patients are particularly vulnerable. Older age, preponderance in males, increased likelihood of comorbid cardiovascular diseases, and increased risk of respiratory dysfunction had all been cited as potential risk factors for worse outcomes in this patient population, particularly patients with Parkinson disease, from COVID-19. Furthermore, it has been reported that patients with PD may have cognitive and motor inflexibility, impaired activation of stress response mechanisms, and a susceptibility to adverse effects of social isolation and loss of physical activity that render them less likely to cope well with the consequences of this pandemic [5,6,9]. Up until recently, however, systematic data did not show an apparent increased risk of contracting COVID-19 or for worse outcomes of the disease in people with PD [5,6]. A community-based observational study of 141 patients with Parkinson disease in Lombardy, one of the most heavily affected regions in Italy by COVID-19, yielded 12 cases or an 8.5% incidence of infection [14]. The authors noted that there were no deaths from COVID-19 in their cohort, and patients manifested primarily with mild to moderate symptoms not requiring hospitalization except for one patient. On the other hand, Antonini and colleagues reported on the outcomes of 10 PD patients affected by COVID-19 at the Parkinson and Movement Disorders unit in Italy and at King’s College Hospital in London, and suggested that PD patients, particularly those who are older and on advanced therapies, should be considered as a specifically susceptible group because of the high mortality rate noted for this subset of patients in their series [15].
Our study provides information on a cohort that is three times larger than that of the previously cited articles, collected within a similar span of time. Our cohort, however, includes a wide variety of patients with movement disorders and not exclusively patients with a diagnosis of PD. Regardless, in this series, we found that within a Movement Disorders subspecialty practice, 81% of the patients who developed COVID-19, and 85% of the patients who died, were people with PD or a parkinsonism. Whether this is because of an actual increased risk of COVID-19 in patients with Parkinson disease, or whether it is because Movement Disorders programs tend to see more people with PD than other movement disorders, is difficult to ascertain. At the CFMDC, people with PD and parkinsonism comprise one third of all the patients we see at all three of our locations, which is disproportionate to the number of patients with parkinsonism who developed COVID-19 in this cohort.
Similar to the observations in patients who developed COVID-19 in the general population, our cohort was predominantly male (64%), 60 years of age or older (89%), had high-risk comorbidities for COVID-19 (78%), and most resided at an extended care facility (64%). Of note, twenty-one (58%) of the patients in this cohort also had comorbid dementia. A recent retrospective study of 627 subjects admitted to an acute hospital in northern Italy yielded 82 patients (13%) who carried a prior diagnosis of dementia, but with a staggering 62% mortality rate, as compared to 26% in patients without dementia at the same institution [16]. Of the thirteen patients in our cohort who died, nine (69%) had comorbid dementia. The overall mortality rate in our cohort for patients with comorbid dementia was 43%. This was higher than the mortality rate of patients with a parkinsonism in this cohort, which was 37%. In comparison, a study of 191 inpatients with COVID-19 in Wuhan, China, yielded a mortality rate of 67% for those with known high-risk medical comorbidities, and 33% for those without any of these comorbidities [3]. In two large studies, overall mortality rates for patients with COVID-19 admitted to hospitals in China and the United Kingdom were 28% and 26%, respectively [3,17]. Thus, although dementia and parkinsonism in our cohort were associated with significant mortality, higher than that reported in general populations, the rates were not as high as has been reported in patients with other comorbidities known to correlate with unfavorable outcomes. Within our cohort of patients with movement disorders, factors related to increased mortality were age over 60 years, PD or parkinsonism diagnosis, residing in an extended care facility, comorbid dementia, and comorbid medical conditions.
As regards the clinical manifestation and disease course of patients in this cohort, we found that two-thirds of patients (67%) required hospitalization, almost three times higher than the reported 23% hospitalization rate among the general population in Connecticut [18]. This observation supports the hypothesis that patients with movement disorders are at particular risk for adverse outcomes with COVID-19. In terms of specific clinical presentation, we found that alteration in mental status, generalized weakness, worsening mobility or the motor symptoms of the underlying movement disorder, and hypotension were common manifestations of COVID-19. In this series, fever, cough, dyspnea, and malaise were almost universally present, but 61% presented with alteration in mental status, and 31% with worsening mobility and/or balance as one of the primary symptoms leading to SARS-CoV-2 testing. Encephalopathy has increasingly been recognized as a presenting symptom of COVID-19, and gait instability is a common presentation of hospitalized patients with movement disorders who develop acute infectious-metabolic conditions [19,20,21]. Anosmia was reported by only one patient who did not have a pre-existing diagnosis of a movement disorder but was referred to our program for new-onset cerebellar ataxia. We postulate that patients with a pre-existing parkinsonism or dementia are less likely to report anosmia as a presenting symptom of COVID-19 because many already have long-standing anosmia related to their neurodegenerative condition.
Three of the patients in this series were on amantadine as part of the management of their parkinsonism, and three were on memantine for dementia. There has been an interest in the potential of adamantanes to alter the course of COVID-19 based on their ability to interfere with viroporin protein channels responsible for the release of RNA-viruses from infected cells [22]. Amantadine in particular was also recently discovered to downregulate the expression CTSL gene coding for the cathepsin L, a lysosomal protease involved in SARS-CoV-2 entry into cells [23]. Based on these potential antiviral effects, it was proposed that adamantanes could serve as a potent therapeutic, decreasing the replication and infectivity of the virus, and possibly leading to better clinical outcomes. Rejdak and colleagues then identified 22 patients who tested positive for SARS-CoV-2 and were taking either amantadine or memantine, and reported that none of these patients developed any clinical manifestations of COVID-19, nor did they report any significant change in their neurologic status [24]. In our cohort, we had six patients who were taking adamantanes who developed significant symptoms related to COVID-19, and three of them died.
In summary, our study supports the recommendation that clinicians must remain vigilant for potential acute and chronic complications of COVID-19 when caring for patients with Parkinson disease and other movement disorders because of the inherent vulnerabilities of this patient population. Our cohort yielded several interesting observations that either confirmed or negated previous assumptions and findings reported regarding COVID-19 in patients with PD and other movement disorders. Within a large database of inpatient cases throughout our hospital system, people with PD and parkinsonism accounted for only 2% of patients admitted for COVID-19. However, for patients with movement disorders, the likelihood of hospitalization after contracting COVID-19 was three times higher than that of the general population. Furthermore, we found that older age, PD diagnosis, living in an extended care facility, comorbid dementia, and comorbid medical conditions were associated with more serious morbidity and death. Even so, the mortality rate for patients with PD or dementia in this cohort was significantly less than the mortality previously reported in patients with other high-risk comorbidities, although higher than that reported in general populations. We also noted that patients with movement disorders frequently presented with altered mental status, generalized weakness, or worsening mobility, but not anosmia, as the initial symptoms of COVID-19. Lastly, within this limited dataset, we did not observe that amantadine or memantine afforded distinct protective properties against COVID-19, as was suggested in the paper by Redjak et al. [24].