New-Onset Chorea Post-COVID-19 Infection: A Case Report

Although the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily involves the cardiovascular and respiratory systems, neurological manifestations, including movement disorders such as myoclonus and cerebellar ataxia, have also been reported. However, the occurrence of post-SARS-CoV-2 chorea is rare. Herein, we describe a 91-year-old female with a past medical history of hypothyroidism who developed chorea after two weeks of contracting a mild coronavirus disease (COVID-19).


Introduction
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel respiratory virus that emerged in 2019 and caused a global pandemic called COVID-19. While this virus primarily affects the cardiorespiratory system, post-infectious neurological complications are not uncommon [1,2]. Though neurocognitive impairment and olfactory neuropathy are among the most common neurologic complications, meningitis, encephalitis, Guillan-Barre syndrome, strokes, and movement disorders, including myoclonus, ataxia, and action tremor, have also been reported [2,3]. However, the occurrence of post-SARS-CoV-2 chorea is rare, and to our knowledge, there have been less than 20 cases reported in the literature.
This article was previously presented as a meeting abstract at the XXVIII World Congress on Parkinson's Disease and Related Disorders on May 15, 2023.

Case Presentation
A 91-year-old female was referred to our clinic for evaluation of abnormal involuntary movements. Six months before the evaluation, she had a bout of mild flu-like symptoms (cough, rhinorrhea, fatigue) and was diagnosed with COVID-19 after testing positive for coronavirus by reverse-transcription polymerase chain reaction (RT-PCR) nasopharyngeal swab. She did not require admission from the infection and recovered in home isolation without medical intervention. She had also received two previous COVID-19 (MODERNA) vaccines about 10 months prior to her presentation.
Two weeks after the flu-like symptoms, she developed excessive involuntary movements of the tongue, jaw, and face. Over the ensuing months, she developed excessive movements involving the arms, legs, and torso. She had no family history of a movement disorder, no personal history of anti-dopaminergic medications, tobacco, or alcohol, and her past medical history was significant only for hypothyroidism. She lived alone and was able to perform her activities of daily living before the onset of these involuntary movements. Systemic and neurological examinations were normal, except for choreiform movements in the face and bilateral upper and lower extremities, albeit her left side was more predominantly affected, as shown in Video 1.

VIDEO 1: Generalized chorea albeit left hemibody predominant
View video here: https://vimeo.com/837946508?share=copy Extensive diagnostic testing for chorea including complete blood count with peripheral smear, comprehensive metabolic panel, thyroid studies, serum paraneoplastic panels, and neuroimaging with computed tomography of the head ( Figure 1) and magnetic resonance imaging of the brain was all unremarkable. Genetic testing for Huntington's disease was not performed at the patient's request. She was started on tetrabenazine 6.25 mg daily, six months after the onset of choreiform movements, and experienced more than 90% improvement in both facial and appendicular symptoms at one month and oneyear follow-up (Video 2) Discussion SARS-CoV-2 relies on the angiotensin-converting enzyme 2 (ACE-2) receptor for entry into the cells and affects the central nervous system likely through transmission via the olfactory nerve and or dissemination from the respiratory tract via the vagus nerve to the brainstem (nucleus solitarius and nucleus ambiguus in the medulla oblongata and midbrain) [2,4]. Concerning COVID-19-associated movement disorders, two mechanisms have been postulated: a) virus-induced gliosis and cellular vacuolation and b) striatal ACE-2 receptor downregulation, causing an imbalance of norepinephrine and dopamine [5].
Chorea is a hyperkinetic movement disorder characterized by involuntary, sudden, brief, and irregular movements. Sydenham's chorea is the most common para/postinfectious entity due to autoimmunity against the basal ganglia post-streptococcal infection [1]. On the other hand, the pathogenesis of COVID-19-associated chorea is poorly understood. It is thought to be secondary to autoimmune antibodies against brain structures such as basal ganglia, on the lines of Sydenham's chorea. Some authors have also suggested that localized hyperviscosity and focal endotheliopathy from the spike protein in the basal ganglia and thalamus contribute to neuronal dysfunction and the generation of chorea [4,6,7].
We have summarized the cases published so far with para/post-COVID-19 chorea in Table 1. The age of onset varied from eight years to 91 years, with our patient being the oldest to have developed post-COVID chorea at 91 years. In most cases, chorea developed following the onset of COVID-19 symptoms with the longest interval between the onset of chorea and COVID-19 symptoms being three months. However, there have been situations when chorea has developed along with or even preceding COVID-19 symptoms.  Choreiform movements can be generalized or prefer one side even with a paucity of a structural lesion. With regards to COVID-19 vaccination, movement disorders' frequency of occurrence is low (0.00002-0.0002), and tremor was the most reported side effect [2]. Salari et al. described two cases of chorea as a side effect of COVID-19 vaccination [1]. Neuroimaging can be normal but can show changes predominantly in the striatum and cerebellum [11][12][13]. Therapeutic options can range from tetrabenazine (most common), antipsychotics such as risperidone, haloperidol, immunomodulation with steroids, intravenous immunoglobulin, and to less common valproate and carbamazepine. Most cases have shown improvement and/or resolution with time.

Conclusions
Even though chorea is rare, clinicians should be aware of it as a possible sequela of COVID-19 infection and in certain cases with vaccination. Our case also highlights that chorea post-COVID-19 is independent of the severity of COVID-19 infection.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other