Parkinson disease following COVID‐19: Report of six cases

Abstract

Background and purpose Core clinical manifestations of COVID‐19 include influenza‐like and respiratory symptoms. However, it is now evident that neurological involvement may occur during SARS‐CoV‐2 infection, covering an extensive spectrum of phenotypical manifestations. A major challenge arising from this pandemic is represented by detecting emerging neurological complications following recovery from SARS‐CoV‐2 infection. To date, a few post‐COVID‐19‐infected subjects diagnosed with Parkinson disease (PD) have been described, raising the possibility of a connection between the infection and neurodegenerative processes. Here, we describe a case series of six subjects who developed PD after COVID‐19. Methods Patients were observed at Scientific Institute for Research and Health Care Mondino Foundation Hospital, Pavia (Italy), and San Paolo University Hospital of Milan (Italy) between March 2021 and June 2022. In all subjects, SARS‐CoV‐2 infection was confirmed by means of reverse transcriptase polymerase chain reaction from a nasopharyngeal swab. Subjects underwent an accurate neurological evaluation, and neuroimaging studies were performed. Results We describe six subjects who developed PD with an average time window after SARS‐CoV‐2 infection of 4–7 weeks. Apparently, no relationship with COVID‐19 severity emerged, and no overt structural brain abnormalities were found. All subjects experienced unilateral resting tremor at onset and showed a satisfactory response to dopaminergic treatment. Conclusions Immune responses to SARS‐CoV‐2 infection have been shown to shape the individual susceptibility to develop long‐term consequences. We hypothesize that, in these subjects, COVID‐19 has unmasked a latent neurodegenerative process. Characterization of the neuroinflammatory signatures in larger cohorts is warranted, which might provide novel insights into the pathogenesis of PD.

SARS‐CoV‐2 cannot unmask Parkinson's disease if there was none before infection

“…It is also contradictory to claim that all patients had received a full three-dose COVID-19 vaccination regimen and to mention in the next sentence that patients 1, 4, 5, and 6 had not been vaccinated before the onset of COVID-19 [1]. The patients' vaccination status should be clarified.…”

“…We read with interest the article by Calculli et al on a case series of six patients who developed Parkinson's disease (PD) 3-8 weeks after SARS-CoV-2 infection [1]. One patient had severe COVID-19 and required mechanical ventilation (patient 1) and another patient had moderate COVID-19 (patient 4) and required steroids [1]. Five patients presented with neurological manifestations other than PD [1].…”

Dopamine Transmission Imbalance in Neuroinflammation: Perspectives on Long-Term COVID-19

“…Recent data describe an exacerbation of PD symptomatology following SARS-CoV-2 infection [ 201 ]. Most interestingly, evidence of PD signs in previously undiagnosed people has been reported [ 9 , 10 , 61 ]. The frequency of encephalopathy in the context of COVID-19 seems to vary widely [ 202 ]; however, the close proximity between new-onset parkinsonisms and a COVID-19 diagnosis, and the presence of simultaneous encephalopathy in some patients, makes to hypothesize an etiological connection [ 9 ].…”

“…SARS-CoV-2 virus, the causative agent of COVID-19, does not cause evident neuropathological alterations in infected cells, such as necrotic changes or other cytological alterations [ 8 ]; however, a direct impact on the brain has been reported and seems to aggravate PD symptoms or trigger PD-like signs probably via an alteration of dopamine neurotransmission. In this sense, clinical data report describe a reduction in dopamine uptake in the putamen or in the striatum of people who have been infected with SARS-CoV-2 virus, which demonstrates nigrostriatal dysfunction [ 9 , 10 ]. Such cumulative damage seems to be dependent on an action of proinflammatory cytokines and chemokines on the mechanisms of dopamine release more than a direct viral effect on the substantia nigra.…”

SARS-CoV-2 N-protein induces the formation of composite α-synuclein/N-protein fibrils that transform into a strain of α-synuclein fibrils

“…For some viruses this is well established in case studies or on an epidemiological level. [14][15][16][17][18] In the context of the covid pandemic, first cases that connect SARS-CoV-2 infections to the development of Parkinson's disease (PD) have indeed been reported. We have recently presented results that point toward direct interactions between the N-protein of SARS-CoV-2 and α-synuclein as a molecular basis for the observed relation between SARS-CoV-2 infections and Parkinsonism.…”