Coronavirus Disease 2019 and Related Parkinsonism: The Clinical Evidence Thus Far

BACKGROUND: The Coronavirus disease 2019 (Covid‐19) pandemic has fueled both research and speculation, as to whether it could be a “perfect storm” for a post‐Covid emergence of parkinsonism in some susceptible individuals, analogous to the post‐encephalitic parkinsonism reported after the 1918 influenza epidemic. This theory is further augmented by reports of a pathogenic effect of the Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2) on the central nervous system with specific impact on the dopaminergic pathway, as well as the possibility of the virus to selectively bind to Angiotensin‐Converting Enzyme‐2 (ACE‐2); these molecules are expressed abundantly in the midbrain dopamine neurons and, are likely involved in several cellular mechanisms cited in Parkinson's Disease (PD) pathophysiology. OBJECTIVES—METHODS: Therefore, we performed a review of the literature up to February 2022 to explore the current landscape considering published cases of new‐onset parkinsonism after a SARS‐CoV‐2 infection in otherwise healthy individuals. We summarized their clinical features, diagnostic and treatment approaches, discussing potential underlying mechanisms in light of PD pathogenesis theories. RESULTS: Twenty cases that developed parkinsonian features simultaneously or shortly after a reported SARS‐CoV‐2 infection were reviewed. In 11 of them, parkinsonism appeared in the context of encephalopathy, while four patients developed post‐infectious parkinsonism without encephalopathy, and four bore similarities to idiopathic PD. Nine patients exhibited a good response to dopaminergic therapy, while four responded to immunomodulatory treatment. CONCLUSIONS: Available data does not yet justify a clear association between the Covid‐19 pandemic and a parkinsonism wave. However, vigilance is necessary, as long‐term effects might have not been revealed.