The prodromal signs of Parkinson's disease (and other synucleinopathies) can present decades before overt CNS manifestions emerge (such as tremor and bradykinesia). These early signs include autonomic dysfunction, gastrointestinal problems and REM sleep behavioral disorder (characterized by lack of muscle atonia during REM sleep leading to the acting out of dreams). Though these symptoms are associated with synucleinopathies of the peripheral nervous system, the disease in its prodromal stage usually goes undiagnosed. New diagnostic techniques (immunohistochemical methods and RT-QuIC) have shown promise in the early detection but they have not yet recieved widespread adoption outside of research settings. At the same time, the lack of accurate longitudinal data to track the full clinical course of synucleinopathies has limited research into this area. Nevertheless, synucleinopathies very clearly present with a high degree of heterogeneity, can affect both the peripheral and central nervous system and often progress slowly.

Given the similarities between the symptomatology of long COVID and peripheral manifestations of synucleinopathies, the increase in REM sleep behavioral disorder, findings of phosphorylated alpha-synuclein in skin biopsies and the amyloidogenicity of SARS-CoV-2, there is a strong argument for focusing research to verify these preliminary findings. If long COVID is indeed caused by a synucleinopathy, it will have major implications for public health and other policy decisions. People should be informed of this potential risk sooner rather than later.