Long-term Risk of Parkinson Disease Following Influenza and Other Infections

Cocoros, Noelle M; Svensson, Elisabeth; Szépligeti, Szimonetta Komjáthiné; Vestergaard, Søren Viborg; Szentkúti, Péter; Thomsen, Reimar Wernich; Borghammer, Per; Sørensen, Henrik Toft; Henderson, Victor W.

doi:10.1001/jamaneurol.2021.3895

Cited by 60 publications

(57 citation statements)

References 55 publications

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“…In a population-based casecontrol study in Canada, a significant association was reported to exist between a history of severe influenza and PD [88]. Recently, a case-control study based on the data of over 60 000 individuals from the Danish National Patient Registry showed that a history of influenza was significantly associated with a later occurrence of PD [89]. In addition, the Spanish flu (influenza A subtype H1N1) has been considered to be a risk factor for a later PD occurrence.…”

Section: Viral Infections Pd and H 2 S Producing Gut Bacteriamentioning

confidence: 99%

Hydrogen Sulfide Produced by Gut Bacteria May Induce Parkinson’s Disease

Murros

2022

Cells

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Several bacterial species can generate hydrogen sulfide (H2S). Study evidence favors the view that the microbiome of the colon harbors increased amounts of H2S producing bacteria in Parkinson’s disease. Additionally, H2S can easily penetrate cell membranes and enter the cell interior. In the cells, excessive amounts of H2S can potentially release cytochrome c protein from the mitochondria, increase the iron content of the cytosolic iron pool, and increase the amount of reactive oxygen species. These events can lead to the formation of alpha-synuclein oligomers and fibrils in cells containing the alpha-synuclein protein. In addition, bacterially produced H2S can interfere with the body urate metabolism and affect the blood erythrocytes and lymphocytes. Gut bacteria responsible for increased H2S production, especially the mucus-associated species of the bacterial genera belonging to the Desulfovibrionaceae and Enterobacteriaceae families, are likely play a role in the pathogenesis of Parkinson’s disease. Special attention should be devoted to changes not only in the colonic but also in the duodenal microbiome composition with regard to the pathogenesis of Parkinson’s disease. Influenza infections may increase the risk of Parkinson’s disease by causing the overgrowth of H2S-producing bacteria both in the colon and duodenum.

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Section: Viral Infections Pd and H 2 S Producing Gut Bacteriamentioning

confidence: 99%

Hydrogen Sulfide Produced by Gut Bacteria May Induce Parkinson’s Disease

Murros

2022

Cells

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“…The role of H1N1 as a susceptibility agent has been recently validated in a retrospective study examining risk for developing Parkinson’s disease in humans following influenza 40 . This study showed that previous influenza infection resulted in the risk for developing Parkinson’s disease increased by 173% compared to individuals not infected 40 . This increase susceptibility was within the confidence interval determined epidemiologically for people born during the time of the 1918 H1N1 pandemic 41 .…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, using a similar approach to this study, we previously showed that mice that recovered from an influenza (strain ca/09 H1N1) infection developed enhanced susceptibility to the parkinsonian toxin MPTP 39 . The role of H1N1 as a susceptibility agent has been recently validated in a retrospective study examining risk for developing Parkinson’s disease in humans following influenza 40 . This study showed that previous influenza infection resulted in the risk for developing Parkinson’s disease increased by 173% compared to individuals not infected 40 .…”

Section: Discussionmentioning

confidence: 99%

COVID-19 infection enhances susceptibility to oxidative-stress induced parkinsonism

Smeyne

Eells

Chatterjee

et al. 2022

Preprint

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Background: Viral induction of neurological syndromes has been a concern since parkinsonian-like features were observed in patients diagnosed with encephalitis lethargica subsequent to the 1918 influenza pandemic. Given the similarities in the systemic responses following SARS-CoV-2 infection with those observed after pandemic influenza, there is a question if a similar syndrome of post-encephalic parkinsonism could follow COVID-19 infection. Objectives: To determine if prior infection with SARS-CoV-2 increased sensitivity to a mitochondrial toxin known to induce parkinsonism. Methods: hACE2 mice were infected with SARS-CoV-2 to induce mild to moderate disease. After 31 days recovery, mice were administered a non-lesion inducing dose of the parkinsonian toxin MPTP. Subsequent neuroinflammation and SNpc dopaminergic neuron loss was determined and compared to SARS-CoV-2 or MPTP alone. Results: hACE2 mice infected with SARS-CoV-2 or MPTP showed no SNpc DA neuron loss following MPTP. In mice infected and recovered from SARS-CoV-2 infection, MPTP induced a 23% or 19% greater loss of SNpc dopaminergic neurons than SARS-CoV-2 or MPTP, respectively (p < 0.05). Examination of microglial activation showed a significant increase in the number of activated microglia in the SARS-CoV-2 + MPTP group compared to SARS-CoV-2 or MPTP alone. Conclusions: Our observations have important implications for long-term public health, given the number of people that have survived SARS-CoV-2 infection as well as for future public policy regarding infection mitigation. However, it will be critical to determine if other agents known to increase risk of PD also have synergistic effects with SARS-CoV-2 and if are abrogated by vaccination.

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“…In this paper we presented two approaches to demonstrate the importance of reporting complete procedures of identifying patients from the DNPR. In practice, other approaches can be used, for example, researchers might identify patients who had a primary or a secondary diagnosis of a disease of interest, 13 patients who had a primary diagnosis of disease of interest leaving alone other kinds of information. 14 , 15 Which approach should be used depends on type of disease and purpose of research and needs to be explored further, which was, however, beyond the scope of this study.…”

Section: Discussionmentioning

confidence: 99%

Importance of Reporting Complete Procedures of Identifying Patients from the Danish National Patient Registry: The Case of Neonatal Jaundice and Epilepsy

Sun¹,

Dreier²,

Wu³

et al. 2022

CLEP

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Objective The Danish National Patient Registry (DNPR) is a valuable resource for medical and epidemiological Research. However, not all research articles fully described procedures they used to identify events. In this study, we compared two approaches in identifying persons with a disease diagnosis using neonatal jaundice and epilepsy as examples. Methods A cohort of singletons born alive between the 1st January 1997 and the 30th November 2016 in Denmark was used for this purpose. Diagnostic information for a hospital contact in the registry included a primary diagnosis, secondary diagnoses, referral diagnoses, and additional information to a diagnosis (associated diagnoses), if any. Approach 1 identified patients of interest by considering all diagnostic information with exclusion of referral diagnoses only. Approach 2 identified patients of interest by additionally excluding diagnoses from a hospital contact that were coded with Z00 – Z99 of ICD-10 (for health service on examination and reproduction, etc.) as the main reason of the hospital contact. We presented the proportion of people with a diagnosis of neonatal jaundice and epilepsy by the two approaches and explored the potential explanations for the difference. Results For the example of neonatal jaundice, the study population included N=1,186,683 persons. The proportion of children with a diagnosis of neonatal jaundice was 5.5% (n=66,736) by approach 1 and 3.9% (n=45,928) by approach 2. For the example of epilepsy, the study population included N=1,183,273 persons. The proportion of children with a diagnosis of epilepsy were 1.2% (n=14,604) by approach 1 and 0.9% (n=10,441) by approach 2. Discussion This study demonstrated that the two approaches identified different proportion of persons with a diagnosis of neonatal jaundice and epilepsy. We advocated researchers report complete procedures of identifying patients for making research findings reproducible and comparable.

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Long-term Risk of Parkinson Disease Following Influenza and Other Infections

Cited by 60 publications

References 55 publications

Hydrogen Sulfide Produced by Gut Bacteria May Induce Parkinson’s Disease

Hydrogen Sulfide Produced by Gut Bacteria May Induce Parkinson’s Disease

COVID-19 infection enhances susceptibility to oxidative-stress induced parkinsonism

Importance of Reporting Complete Procedures of Identifying Patients from the Danish National Patient Registry: The Case of Neonatal Jaundice and Epilepsy

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