The Influence of Coronavirus Disease-2019 (COVID-19) On Parkinson’s Disease: An Updated Systematic Review

  1. Vikash Jaiswal
  2. Danah Alquraish
  3. Zouina Sarfraz
  4. Shavy Nagpal
  5. Prakriti Singh Shrestha
  6. Dattatreya Mukherjee
  7. Prathima Guntipalli
  8. Azza Sarfraz
  9. Diana F Sánchez Velazco
  10. Arushee Bhatnagar
  11. Saloni Savani
  12. Elmjedina Halilaj
  13. Samir Ruxmohan
  14. Wilson Cueva

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Abstract

Background

COVID-19 has affected global communities with multiple neurological complications in addition to other critical medical issues. COVID-19 binds to the host’s angiotensin-converting enzyme2 (ACE2) receptors, which are expressed in the neurons and glial cells, acting as an entry port to the central nervous system (CNS). ACE2 receptors are abundantly expressed on dopamine neurons, which may worsen the prognosis of motor symptoms in Parkinson’s disease (PD). SARS-CoV-2 may lead to an indirect response via immune-mediated cytokine storms and propagate through the CNS leading to damage. PD is also been associated with certain post-viral infections apart from COVID-19, such as HSV, Influenzavirus A, Measles virus, Cytomegalovirus, and Mumps.

Objective

In this systematic review, we aim to provide a thorough analysis of associations between COVID-19 and neurological outcomes for patients with PD.

Methods

Using PRISMA statement 2020, a systematic review was conducted to isolate confirmed COVID-19 patients and analyze the PD-associated neurological outcomes. A systematic literature search was conducted using the following databases: PubMed, Science Direct, Google Scholar, and Cochrane databases. The following keywords were used “COVID19, SARS-CoV-2, Parkinson’s disease, Pandemic, Mortality.” A modified Delphi process was employed to include the studies and ensure that the clinical outcome measures were addressed.

Results

Of the 355 records located during the initial round of screening, 16 were included in the final synthesis. Of PD patients who tested positive for SARS-CoV-2, worsening motor symptoms and other viral-associated symptoms were reported. These symptoms included bradykinesia, tremors, gait disturbances, delirium and dementia, and severe spasms of arms and legs. Encephalopathy was presented in two of the included studies. Increased mortality rates were identified for hospitalized patients due to COVID-19 and PD as compared to other patient groups, albeit with limited generalizability due to high bias of included studies.

Conclusion

Patients with PD may experience substantial worsening of motor and non-motor symptoms due to COVID 19. Given the novelty of neurological-viral associations, clinical studies in the future ought to explore the disease severity and neurological outcomes in COVID-19 positive patients with PD as compared to non-PD patients, in addition to understanding the role of ACE2 in increased vulnerability to contracting the infection and as a treatment modality.

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  1. Version published to 10.1101/2021.05.09.21256929v3 on medRxiv
  2. ScreenIT

    SciScore for 10.1101/2021.05.09.21256929: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    We did an extensive search on databases namely PubMed central, Google Scholar, Cochrane, Science Direct and EMBASE for open access studies.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    Google Scholar
    suggested: (Google Scholar, RRID:SCR_008878)
    EMBASE
    suggested: (EMBASE, RRID:SCR_001650)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    The major limitation for this systematic review is the presence of confounder factors as the majority of the Parkinson’s diseases patients are elderly with other comorbidities. Also the duration of the diseases and the severity of the symptoms may influence the clinical outcome of covid-19 infection. Important information including patients medication compliance which might affect the coveted 19 infection outcome were lacking as well.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.05.09.21256929v2 on medRxiv
  4. Version published to 10.1101/2021.05.09.21256929v1 on medRxiv
  5. Version published to 10.1177/21501327211039709