New‐onset neurodegenerative diseases as long‐term sequelae of SARS‐CoV‐2 infection: A systematic review and meta‐analysis

Rahmati, Masoud; Yon, Dong Keon; Lee, Seung Won; Soysal, Pınar; Koyanagi, Ai; Jacob, Louis; Li, Yusheng; Park, Jong Mi; Kim, Yong Wook; Smıth, Lee; Smith, Lee

doi:10.1002/jmv.28909

Cited by 26 publications

(14 citation statements)

References 38 publications

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“…Other mechanisms that may impact both retina and brain are populations of microglia that reflect specific niches and phases of neurodegenerative disease, infiltration by circulating immune cells, long-term effects of prior infection, and the impact of microbiota on inflammation and nutrient absorption. 65 – 67 Some of these processes may be visible in the retina with new imaging technologies.…”

Section: Discussionmentioning

confidence: 99%

Outer Retinal Thickness Is Associated With Cognitive Function in Normal Aging to Intermediate Age-Related Macular Degeneration

Owsley,

McGwin,

Swain

et al. 2024

Invest. Ophthalmol. Vis. Sci.

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Purpose Research on Alzheimer's disease (AD) and precursor states demonstrates a thinner retinal nerve fiber layer (NFL) compared to age-similar controls. Because AD and age-related macular degeneration (AMD) both impact older adults and share risk factors, we asked if retinal layer thicknesses, including NFL, are associated with cognition in AMD. Methods Adults ≥ 70 years with normal retinal aging, early AMD, or intermediate AMD per Age-Related Eye Disease Study (AREDS) nine-step grading of color fundus photography were enrolled in a cross-sectional study. Optical coherence tomography (OCT) volumes underwent 11-line segmentation and adjustments by a trained operator. Evaluated thicknesses reflect the vertical organization of retinal neurons and two vascular watersheds: NFL, ganglion cell layer–inner plexiform layer complex (GCL-IPL), inner retina, outer retina (including retinal pigment epithelium–Bruch's membrane), and total retina. Thicknesses were area weighted to achieve mean thickness across the 6-mm-diameter Early Treatment of Diabetic Retinopathy Study (ETDRS) grid. Cognitive status was assessed by the National Institutes of Health Toolbox cognitive battery for fluid and crystallized cognition. Correlations estimated associations between cognition and thicknesses, adjusting for age. Results Based on 63 subjects (21 per group), thinning of the outer retina was significantly correlated with lower cognition scores ( P < 0.05). No other retinal thickness variables were associated with cognition. Conclusions Only the outer retina (photoreceptors, supporting glia, retinal pigment epithelium, Bruch's membrane) is associated with cognition in aging to intermediate AMD; NFL was not associated with cognition, contrary to AD-associated condition reports. Early and intermediate AMD constitute a retinal disease whose earliest, primary impact is in the outer retina. Our findings hint at a unique impact on the brain from the outer retina in persons with AMD.

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Section: Discussionmentioning

confidence: 99%

Outer Retinal Thickness Is Associated With Cognitive Function in Normal Aging to Intermediate Age-Related Macular Degeneration

Owsley,

McGwin,

Swain

et al. 2024

Invest. Ophthalmol. Vis. Sci.

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“…Among the patients, respiratory, cardiovascular, immunological, oncological, metabolic, and renal diseases were detected that were either newly developed or only newly detected (not diagnosed or at least noted on medical records) before the acute episode of COVID-19. Others also found new-onset neurodegenerative diseases as long-term sequelae of SARS-CoV-2 infection, pointing towards the need of increased awareness of potential COVID-19-driven onset of different disorders [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

Co-Morbidity Clusters in Post-COVID-19 Syndrome

Sárközi,

Tornyi,

Békési

et al. 2024

JCM

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Background: Post-COVID-19 syndrome, characterized by persistent symptoms emerging more than 12 weeks after acute infection, displays diverse manifestations. This study aimed to analyze co-existing organ dysfunctions in post-COVID-19 patients and explore their potential association with the acute COVID-19 episode and functional impairment. Methods: Data from 238 patients attending post-COVID-19 outpatient care between 1 March 2021 and 1 March 2022, after previous hospitalization for acute COVID-19, were retrospectively analyzed with 80 having comprehensive mapping of organ involvement. Results: The average time between acute episode and post-COVID-19 care was 149 days. Spirometry indicated significant abnormalities in lung function. Predominant symptoms included respiratory (75%), fatigue (73%), neurological (62.5%), and ear-nose-throat issues (51.25%). Multiorgan dysfunctions were observed in 87.5% of patients, contributing to an 18.33% reduction in health quality compared to pre-acute COVID-19 levels. Subgroup analysis identified four distinct post-COVID-19 syndrome subgroups, highlighting the coexistence of respiratory and neurological disorders as potential indicators and drivers of further organ involvement. Our results reveal that most patients with post-COVID-19 syndrome suffer from multiorgan disorders. Conclusions: The presence of coexisting respiratory and neurological symptoms suggests the involvement of other organ systems as well. The complexity of multiorgan involvement requires further studies to provide insights into the different symptom clusters and identify potential targets for personalized preventive and therapeutic interventions to improve patient outcome.

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“…Previous authors have pointed at a possible association between SARS-CoV-2 infection and neurodegeneration, as identified by a rise in the incidence of cognitive decline and parkinsonism in survivors [28,[32][33][34]. A recent imaging study of COVID19+ subjects, including those with mild disease, revealed reductions in grey matter thickness in olfaction-related structures as well as other regions functionally connected to the olfactory cortex [15].…”

Section: Discussionmentioning

confidence: 99%

Neuropathological assessment of the olfactory bulb and tract in individuals with COVID-19

Lengacher,

Tomlinson,

Jochum

et al. 2023

Preprint

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SummaryThe majority of patients with Parkinson disease (PD) experience a loss in their sense of smell and accumulate insoluble α-synuclein aggregates in their olfactory bulbs (OB). Subjects affected by a SARS-CoV-2-linked illness (COVID-19) frequently experience hyposmia. We previously hypothesized that α-synuclein and tau misprocessing could occur following host responses to microbial triggers. Using semiquantitative measurements of immunohistochemical signals, we examined OB and olfactory tract specimens collected serially at autopsies between 2020 and 2023. Deceased subjects comprised 50 adults, which included COVID19+ patients (n=22), individuals with Lewy body disease (e.g., PD and dementia with Lewy bodies (DLB; n=6)), Alzheimer disease (AD; n=3), other non-synucleinopathy-linked degenerative diseases (e.g., progressive supranuclear palsy (PSP; n=2) and multisystem atrophy (MSA; n=1)). Further, we included neurologically healthy controls (HCO; n=9) and those with an inflammation-rich brain disorder as neurological controls (NCO; n=7). When probing for inflammatory changes focusing on anterior olfactory nuclei (AON) using anti-CD68 immunostaining, scores were consistently elevated in NCO and AD cases. In contrast, inflammation on average was not significantly altered in COVID19+ patients relative to controls, although anti-CD68 reactivity in their OB and tracts declined with progression in age. Mild-to-moderate increases in phospho-αSyn and phospho-tau signals were detected in the AON of tauopathy-and synucleinopathy-afflicted brains, respectively, consistent with mixed pathology, as described by others. Lastly, when both sides were available for comparison in our case series, we saw no asymmetry in the degree of pathology of the left versus right OB and tracts. We concluded from our autopsy series that after a fatal course of COVID-19, microscopic changes -when present-in the rostral, intracranial portion of the olfactory circuitry generally reflected neurodegenerative processes seen elsewhere in the brain. In general, inflammation correlated best with the degree of Alzheimer’s-linked tauopathy and declined with progression of age in COVID19+ patients.

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New‐onset neurodegenerative diseases as long‐term sequelae of SARS‐CoV‐2 infection: A systematic review and meta‐analysis

Cited by 26 publications

References 38 publications

Outer Retinal Thickness Is Associated With Cognitive Function in Normal Aging to Intermediate Age-Related Macular Degeneration

Outer Retinal Thickness Is Associated With Cognitive Function in Normal Aging to Intermediate Age-Related Macular Degeneration

Co-Morbidity Clusters in Post-COVID-19 Syndrome

Neuropathological assessment of the olfactory bulb and tract in individuals with COVID-19

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