SARS-CoV-2 and the risk of Parkinson’s disease: facts and fantasy

During the pandemic it has become clear that severe acure respiratory syndrome coronavirus (SARS-CoV-2) causes not just respiratory disease, but can affect multiple organs and tissues. Of note is the involvement of the CNS and PNS, and the fact that this involvement is independent from the severity of the respiratory disease. Acute and subacute neurological complications of SARS-CoV-2 infections are reported in up to 85% of patients, including those with severe COVID-19, but also in otherwise minimally symptomatic or asymptomatic people. As many as 65% of people with COVID-19 present with hyposmia, which is also a common premotor symptom in Parkinson’s disease. This symptom, added to the fact that parkinsonism has been reported following COVID-19, has drawn the attention of the medical community to the hypothetical link between SARS-CoV-2 infection and Parkinson’s disease.

So far, three cases of parkinsonism have been reported after SARS-CoV-2 infection. Their clinical details are important for evaluating whether or not parkinsonism is causally related with COVID-19. The three patients are relatively young (two men aged 45 and 58 years, and a woman aged 35 years). The men had hypertension and were on angiotensin-converting enzyme (ACE) inhibitors, and the younger man also had asthma, whereas the woman was healthy before the infection. In two cases (a male and the female), the sense of smell was affected. None of the male patients had a monogenic cause or known genetic predisposition for Parkinson’s disease, while genetic tests were not done for the female patient. Onset was acute in the three cases (10–32 days after COVID-19 diagnosis); one patient (the 58 year old male) developed akinetic rigid syndrome in the context of a complex neurological presentation compatible with encephalopathy, including myoclonus and opsoclonus, while the other two patients had pure asymmetric akinetic-rigid features, with tremor, and mild respiratory disease. Spontaneous improvement was reported in this patient, with no response to an acute challenge with apomorphine; the female patient responded to short-term levodopa treatment, while the younger male patient had some improvement after treatment with a dopamine agonist and anticholinergics. Functional nigrostriatal neuroimaging was abnormal in all three cases, which implies dopaminergic nigrostriatal impairment, but is not diagnostic of Parkinson’s disease.