3.1. Case 1

A previously healthy 42-year-old man presented with difficulty speaking, cognitive deficits, ataxia, and progressive disabling jerks in upper and lower limbs, leading to falls (see Supplementary video-1). Neurological examination demonstrated spontaneous, action-induced, and tactile-sensitive myoclonus on the face, upper extremities, and lower extremities. He had dysmetria and dysdiadochokinesia with superimposed action-induced myoclonus in the upper and lower extremities. Myoclonus prevented him from standing independently, and he had a wide-based gait. The rest of the neurological examination was normal. Laboratory tests including renal function, liver function, ammonium, urea, and CO2 were normal, except for the nasopharyngeal RT-PCR test for SARS-CoV-2, which was positive. Computed tomography (CT) of the head and brain magnetic resonance imaging (MRI) were normal. Electroencephalogram (EEG) and electromyography (EMG) were performed but did not reveal any abnormalities. Given these findings and the positive SARS-CoV-2 PCR, myoclonus was considered postinfectious. No other symptoms such as fever, myalgia, cough, fatigue, hyposmia, or hypogeusia were present. Cerebrospinal fluid (CSF) analysis was unremarkable, RT-PCR test for SARS-CoV-2 and autoantibodies were negative. He was treated with methylprednisolone 1000 mg IV daily for five days, bringing about a partial resolution of myoclonus. Complete recovery was observed on a follow-up session one month later.

3.2. Case 2

A previously healthy 52-year-old man presented with progressive imbalance and generalized jerks (see Supplementary video-2). A week before, he had experienced myalgia and tested positive for SARS-CoV-2. Upon admission, he had generalized stimulus-sensitive myoclonus affecting his face, hands, and legs, confining him to a wheelchair. Other neurological findings, including eye movements, muscle tone, and deep tendon reflexes, were normal. He did not have any coughing, fever, dyspnea, and O2 saturation was more than 97% without nasal O2. Ground-glass opacities suggestive of SARS-CoV-2 infection were detected on chest CT. Laboratory studies showed no increase in inflammatory markers in peripheral blood; CRP and white blood cell count were normal. Brain CT and MRI were normal. Results from CSF evaluations, including autoantibody investigations, were unremarkable. The cerebellar syndrome improved after high-dose IV methylprednisolone (1 gr/day for five days); on a follow-up session after three weeks, the patient could walk independently.

3.3. Case 3

A 38-year-old man was referred to our clinic with generalized jerks in his hands (see Supplementary video-3). A week before, he had been discharged from the hospital after four days of hospitalization due to a positive nasopharyngeal RT-PCR test and evident involvement of his lungs. Four days after discharge, he developed fine jerks in his hands and could not write; three days later, he was referred to our clinic with progression and generalization of jerks. He had generalized myoclonus in upper and lower limbs and bizarre abnormal movements that diminished with distraction; he was also restless and seemed anxious. The rest of the neurological examinations were normal. Lab tests were unremarkable. Laboratory investigations and brain MRI scans were normal. CSF analyses, including cell count, protein, and autoimmune panel, were normal. Clonazepam (2 mg/day), levetiracetam (1000 mg/day), and IV methylprednisolone for 5 days (1 g/day) were started, resulting in partial improvement. After two weeks, myoclonus was resolved; functional movements improved with some residual deficits, but he was still suffering from anxiety.

4.1. Myoclonus and COVID-19

Infection-associated myoclonus can often be encountered among patients with severe viral, bacterial, or parasitic infections and is characterized by abrupt, brief, and sometimes repetitive contractions of the trunk, limbs, or face muscles [16, 25]. Myoclonus is reportedly the most common movement disorder in hospitalized COVID-19 patients [52]. Given the numerous cases of myoclonus in patients without a remarkable history of abnormal movements (see Table 1) and the close temporal association of myoclonus with COVID-19 symptoms, one could suspect a causal link between the two conditions. Some have also advised monitoring COVID-19 survivors for probable, unfortunate posthypoxic myoclonus as a long-term COVID-19 complication [20]. Mechanistically, SARS-CoV-2 infection is speculated to cause myoclonus through one or any combination of the following: (I) hypoxia and systemic (e.g., metabolic) disturbances and (II) direct invasion of the CNS cells and (III) immune-mediated pathways, such as molecular mimicry with the host’s CNS tissue [24].

4.2. Tremor and COVID-19

Tremor is another type of COVID-19-associated abnormal movement observed in hospitalized COVID-19 patients [52]. We identified 9 cases of tremor occurring in COVID-19 patients, whose clinical and treatment-associated data are described in Table 1 (cases no. 5–10, 25, 39, and 49) [11, 12, 18, 29, 37]. Tremors in PD patients may also exacerbate as a result of a COVID-19 infection [53].

4.3. Ataxia and COVID-19

Despite having been rarely attributed to infections before this pandemic, numerous cases of cerebellar ataxia in COVID-19 patients (during or after their infection course) have raised concerns regarding a potential causal link probably through immune-mediated pathomechanisms [25, 54].

4.4. Chorea Associated with COVID-19

The most recognized chorea associated with infections is Sydenham’s chorea, characterized by autoimmunity against the basal ganglia after a streptococcal infection [55]. We identified only one case of chorea in a COVID-19 patient [10], a 14-year-old girl with previously diagnosed Sydenham chorea when she was 11. She reported no disease activity during the past two years, yet she developed chorea on the third day after COVID-19 symptoms onset. The authors could not conclude whether this was a recurrence of her previously silent disease or an immune-mediated newly developed chorea with a causal link to COVID-19 [10]. However, we assume the latter was less likely, with the very short interval between COVID-19 onset and chorea manifestation (3 days) arguing against an autoimmune scenario.

4.5. Hypokinesia and Parkinsonism: Considerations in COVID-19

The acute hypokinetic-rigid syndrome has been reported in two cases (cases no. 5 [11] and 13 [15]); both developed a severe course of infection and required intensive care and mechanical ventilation.

Parkinson’s disease (PD) is a neurodegenerative disease caused by the destruction of dopaminergic neurons in substantia nigra pars compacta (SNpc). Evidence of viral infections associated with PD exists; thus, vigilant monitoring and investigation of probable links between SARS-CoV-2 infection and parkinsonism may be necessary [7, 56]. On this matter, the presence of antibodies targeting coronaviruses in cerebrospinal fluid of PD patients was more frequently observed when compared to individuals without PD. Further, the proposed ability of coronaviruses in breaching into the CNS via nasal cavity and nasal neuroepithelium can give us more reasons to be concerned [57, 58]. Interestingly, it has been speculated that PD-associated α-synuclein retrograde spreading and aggregation from the olfactory bulb to the midbrain and deeper CNS structures—leading to cellular death of the affected tissue—could offer some protection against SARS-CoV-2 breaching into the CNS via the olfactory route [59]. However, the aforementioned neuropathological data from autopsy studies call this hypothesis into question [8, 9]. Regardless of such hypothesized protective effects, PD patients are nevertheless more vulnerable to complications following respiratory infections, and odds for their hospitalization or development of other comorbidities are higher than the general population [60]. Furthermore, parkinsonian symptoms after viral respiratory infections may hint us toward the less-known sides of the disease etiology and pathogenesis [61].

A community-based case-control study on 12 PD patients who contracted COVID-19 documented a substantial risk of motor and nonmotor symptoms worsening associated with mild to moderate degrees of COVID-19, regardless of the patients’ age and disease duration [7].

Lo Monaco and colleagues reported a patient with an 8-year history of PD who developed severe generalized dystonia shortly after contracting COVID-19. Improvement was achieved after an increase in her daily dose of levodopa and clozapine [62].

Inversely, PD and its associated disabilities may negatively impact the outcome of COVID-19 illness, along with other known risk factors such as age and hypertension. Indeed, Fasano et al. reported a higher COVID-19 mortality rate in community-dwelling PD patients (i.e., not living in nursing homes) than the general population [63], and Salari et al. showed PD patients have a higher proportion of COVID-19 mortality in comparison with other patients hospitalized for COVID-19 [64].

Some limitations apply to the present review article, such as the keywords selection; some studies that have not used the keywords incorporated in our search strategy, e.g., those that only mentioned “neurological manifestations” without further specification, might have been missed. The literature search has not thoroughly adhered to the standards of a systematic review, albeit being as exhaustive and comprehensive as possible. Furthermore, cross-reference checking for some reviewed articles may have been incomplete. Review papers bear the limitation of their reviewed articles; as discussed earlier, myoclonus may stem from metabolic comorbidities in some cases. Thus, the attribution of myoclonus to COVID-19 by some case studies is a potential limitation of such reports applying to the present review as well. Another limitation was that electrophysiological data were not obtained from two of our cases (i.e., Cases 2 and 3).