Implications of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection in Parkinson's disease (PD), particularly worsening of motor and non‐motor symptoms and possibly higher mortality in those with advanced disease, comorbidities, and frailty have been reported in several case series and observational studies. 1 , 2 , 3 , 4 , 5 As time has evolved, the issue of long‐term sequelae in patients affected by coronavirus disease 2019 (COVID‐19), often referred to as “long COVID”, has emerged, and recently, in the United Kingdom, the National Institute for Health and Care Excellence has defined the “post–COVID‐19 syndrome” as “signs and symptoms that develop during or after an infection consistent with COVID‐19, continue for more than 12 weeks and are not explained by an alternative diagnosis.” 6 Here we present the prevalence of post–COVID‐19 syndrome in 27 patients with PD who were affected by COVID‐19 across several centers in the United Kingdom, Italy, Romania, and Mexico from the beginning of March 2020 to present (Table 1). As some of the post–COVID‐19 symptoms may be part of the PD clinical phenomenology, we considered symptoms part of the clinical manifestations of a post–COVID‐19 syndrome only if these occurred after a confirmed SARS‐CoV‐2 infection or in case of an acute or subacute worsening of a preexisting symptom that had been previously stable. In addition, we report on motor worsening and increased levodopa equivalent daily dose requirements within the long‐COVID spectrum. In our series, 23 (85.2%) patients with PD developed post–COVID 19 symptoms (Table 1). We report that the most common long‐term effects of COVID‐19 are worsening of motor function (51.9%) and increased levodopa daily dose requirements (48.2%) followed by fatigue (40.7%); cognitive disturbances (22.2%), including “brain fog”, loss of concentration and memory deficits; and sleep disturbances (22.2%), such as insomnia. Broadly these symptom complexes concur with the existing literature on long COVID in the general population. 7 Interestingly, the severity of COVID‐19, as indicated by a history of hospitalization, did not seem to be the condicio sine qua non for the development of a post–COVID‐19 syndrome in patients with PD. We also believe that in some cases the stress of a prolonged lockdown due to the pandemic and the reduced access to health care and rehabilitation interventions may contribute to the burden of the post–COVID‐19 syndrome in PD. Therefore, post‐COVID clinical manifestations may result from a combination of new symptoms and lockdown as well as viral illness‐related worsening of preexisting PD features.
TABLE 1.
Demographics, PD‐related information, and prevalence of post–COVID‐19 syndrome (n = 27); Data is presented as mean ± standard deviation, median (interquartile range) or number (percentage)
| Outcome measures | Results |
|---|---|
| Sex, male | 16 (59.3%) |
| Race/ethnicity | |
| White | 9 (33.3%) |
| Black | 2 (7.4%) |
| Other | 16 (59.3%) |
| Age at PD diagnosis, years | 59.0 ± 12.7 |
| PD disease duration at time of COVID‐19 diagnosis, years | 9.2 ± 7.8 |
| H&Y stage at COVID‐19 diagnosis | 2.0 (1.0) |
| LEDD at COVID‐19 diagnosis, mg | 1053.5 ± 842.4 |
| Hospitalization due to COVID‐19 | 6 (22.2%) |
| Charlson Comorbidity Index at COVID‐19 diagnosis | 2.0 (1.5) |
| Post–COVID‐19 syndrome | 23 (85.2%) |
| Respiratory symptoms | |
| Breathlessness | 1 (3.7%) |
| Cough | 3 (11.1%) |
| Cardiovascular symptoms | |
| Chest tightness | 0 (0%) |
| Chest pain | 1 (3.7%) |
| Palpitations | 0 (0%) |
| Generalized symptoms | |
| Fatigue | 11 (40.7%) |
| Fever | 5 (18.5%) |
| Pain | 3 (11.1%) |
| Neurological symptoms | |
| Cognitive disturbances a | 6 (22.2%) |
| Headache | 5 (18.5%) |
| Sleep disturbances | 6 (22.2%) |
| Peripheral neuropathy symptoms b | 3 (11.1%) |
| Dizziness | 4 (14.8%) |
| Delirium | 2 (7.4%) |
| Gastrointestinal symptoms | |
| Abdominal pain | 0 (0%) |
| Nausea | 2 (7.4%) |
| Diarrhea | 0 (0%) |
| Reduced appetite | 1 (3.7%) |
| Musculoskeletal symptoms | |
| Joint pain | 3 (11.1%) |
| Muscle pain | 2 (7.4%) |
| Psychological/psychiatric symptoms | |
| Depression | 2 (7.4%) |
| Anxiety | 4 (14.8%) |
| Ear, nose, and throat symptoms | |
| Tinnitus | 0 (0%) |
| Earache | 0 (0%) |
| Sore throat | 0 (0%) |
| Loss of taste or smell | 4 (14.8%) |
| Dermatological | |
| Skin rashes | 0 (0%) |
| PD‐specific aspects | |
| Motor worsening | 14 (51.9%) |
| Increased LEDD requirement | 13 (48.2%) |
Brain fog, loss of concentration, or memory issues.
Pins and needles and numbness.
Abbreviations: PD, Parkinson's disease; COVID‐19, coronavirus disease 2019; SD, standard deviation; IQR, interquartile range; H&Y, Hoehn and Yahr Scale; LEDD, levodopa equivalent daily dose.
In conclusion, this is the first multicenter case series investigating the occurrence of post–COVID‐19 syndrome in patients with PD. The small sample size and the lack of a controlled group make it challenging to draw any firm conclusions; nevertheless, we believe our case series is meaningful as it highlights the possibility of the existence of a post–COVID‐19 syndrome in most patients with PD recovering from acute COVID‐19. There is a clear need for greater awareness of this issue among health care professionals, and further studies are required with longitudinal follow‐up of a larger cohort of patients with PD to address the natural history of the reported symptoms and with a view to developing personalized management strategies.
Author Roles
(1) Research Project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript: A. Writing of the First Draft, B. Review and Critique.
V.L.: 1A, 1B, 1C, 2A, 2B, 2C, 3A, 3B
M.R.V.: 1C, 3B
A. Abundes: 1C, 3B
K.R.: 1C, 3B
J.T.T.: 1C, 3B
C.F.P.: 1C, 3B
L.I.: 1C, 3B
S.R.: 1C, 3B
R.B.: 1C, 3B
A.S.: 1C, 3B
P.O.: 1C, 3B
A. Antonini: 1C, 3B
K.R.C.: 1A, 1B, 2C, 3B
Financial Disclosures of All Authors (for the Preceding 12 Months)
V.L. received honoraria for speaker‐related activities from Bial, Profile, and Britannia Pharmaceuticals. J.T.T. received research support and funding from Office of Life Sciences, InnovateUK, Bristol‐Myers‐Squibb, iRhythm Technologies, and received speaker honorarium from Bristol‐Meyers‐Squibb and Goldman Sachs. P.O. received compensation for lectures and advice from AbbVie, Bial, Britannia, Ever Pharma, Global Kinetics (GKC), Lobsor, Nordic Infucare, and Zambon. R.B. receives salary from Chulalongkorn University and stipend from the Royal Society of Thailand; has received consultancy and/or honoraria/lecture fees from Abbott, Boehringer‐Ingelheim, Britannia, Ipsen, Novartis, Teva‐Lundbeck, Takeda, and Otsuka pharmaceuticals; has received research funding from the Newton Fund, the UK government, Thailand Science, and Research Innovation Bureau, Thailand Research Fund, Crown Property Bureau, Chulalongkorn University, and the National Science and Technology Development Agency; and holds patents for a laser‐guided walking stick, portable tremor device, nocturnal monitoring, and electronic Parkinson's disease symptom diary as well as copyright on Parkinson's mascot, dopamine lyrics and teaching video clips for common nocturnal and gastrointestinal symptoms for Parkinson's disease. A. Antonini has received compensation for consultancy and speaker related activities from Union Chimique Belge (UCB), Boehringer Ingelheim, Britannia, AbbVie, Kyowa Kirin, Zambon, Bial, Neuroderm, Theravance Biopharma, Roche and receives research support from Chiesi Pharmaceuticals, Bial, Lundbeck, Horizon 2020 (Grant 825,785), Horizon2020 (Grant 101,016,902), Ministry of Education University and Research (Grant ARS01_01081), and the Cariparo Foundation. He serves as consultant for Boehringer–Ingelheim for legal cases on pathological gambling. K.R.C. has received honoraria for advisory boards from AbbVie, UCB, Pfizer, Jazz Pharma, GKC, Bial, Cynapsus, Novartis, Lobsor, Stada, Medtronic, Zambon, Profile, Sunovion, Roche, Theravance, and Scion; honoraria for lectures from AbbVie, Britannia Pharmaceuticals, UCB, Mundipharma, Zambon, Novartis, Boehringer Ingelheim, Neuroderm, and Sunovion; grants (investigator initiated) from Britannia Pharmaceuticals, AbbVie, UCB, GKC, and Bial; and academic grants from Innovative Medicines Initiative European Union (IMI EU), Parkinson's UK, National Institute for Health Research, Parkinson's disease non‐motor study group (PDNMSG), European Union (EU) (Horizon 2020), Kirby Laing Foundation, Parkinson's Foundation (PF) (USA), and Medical Research Council (MRC).
Acknowledgments
The views expressed are those of the authors and not necessarily those of the National Health Service (NHS), National Institute for Health Research (NIHR) or Department of Health. The authors acknowledge the support of the International Parkinson and Movement Disorder Society Non‐Motor PD Study Group, the NIHR London South Clinical Research Network, and the NIHR Biomedical Research Centre. This article represents independent collaborative research part funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London. The authors would also like to thank the patients of the King's Electronic Records Research Committee, UK; all clinicians and frontline staff engaged in the care of patients with COVID‐19 and research activity at King's College and Princess Royal Hospitals, London, in particular Daniel van Wamelen, Lucia Batzu, Miriam Parry, Jenny Natividad, Olabisi Awogbemila, Aleksandra Podlewska, Dhaval Trivedi, Jonathon Samuel, Pavlos Zinzalias, Juliet Staunton, and Alexandra Rizos; as well as clinicians and frontline staff at the Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez, Mexico City, Mexico; at the Parkinson and Movement Disorders Unit in Padua, Italy; and at the Department of Neurology, Transilvania University of Brașov, Brașov, Romania.
Relevant conflicts of interests/financial disclosures: Nothing to report.
[The copyright line updated on 05 May 2021, after first online publication.]
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