Long COVID: major findings, mechanisms and recommendations

Nature Reviews Microbiology, Год журнала: 2023, Номер 21(3), С. 133 - 146

Опубликована: Янв. 13, 2023

Язык: Английский

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Long-term neurologic outcomes of COVID-19

Nature Medicine, Год журнала: 2022, Номер 28(11), С. 2406 - 2415

Опубликована: Сен. 22, 2022

Abstract The neurologic manifestations of acute COVID-19 are well characterized, but a comprehensive evaluation postacute sequelae at 1 year has not been undertaken. Here we use the national healthcare databases US Department Veterans Affairs to build cohort 154,068 individuals with COVID-19, 5,638,795 contemporary controls and 5,859,621 historical controls; inverse probability weighting balance cohorts, estimate risks burdens incident disorders 12 months following SARS-CoV-2 infection. Our results show that in phase there was increased risk an array including ischemic hemorrhagic stroke, cognition memory disorders, peripheral nervous system episodic (for example, migraine seizures), extrapyramidal movement mental health musculoskeletal sensory Guillain–Barré syndrome, encephalitis or encephalopathy. We estimated hazard ratio any sequela 1.42 (95% confidence intervals 1.38, 1.47) burden 70.69 63.54, 78.01) per 1,000 persons months. were elevated even people who did require hospitalization during COVID-19. Limitations include comprising mostly White males. Taken together, our provide evidence long-term had

Язык: Английский

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Alzheimer's‐like signaling in brains of COVID‐19 patients

Alzheimer s & Dementia, Год журнала: 2022, Номер 18(5), С. 955 - 965

Опубликована: Фев. 3, 2022

The mechanisms that lead to cognitive impairment associated with COVID-19 are not well understood.Brain lysates from control and patients were analyzed for oxidative stress inflammatory signaling pathway markers, measurements of Alzheimer's disease (AD)-linked biochemistry. Post-translational modifications the ryanodine receptor/calcium (Ca2+ ) release channels (RyR) on endoplasmic reticuli (ER), known be linked AD, also measured by co-immunoprecipitation/immunoblotting brain lysates.We provide evidence linking SARS-CoV-2 infection activation TGF-β overload. neuropathological pathways causing tau hyperphosphorylation typically AD shown activated in patients. RyR2 brains demonstrated a "leaky" phenotype, which can promote behavioral defects.COVID-19 neuropathology includes AD-like features leaky could therapeutic target amelioration some defects long COVID.

Язык: Английский

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COVID-19 and risk of neurodegenerative disorders: A Mendelian randomization study

Translational Psychiatry, Год журнала: 2022, Номер 12(1)

Опубликована: Июль 14, 2022

Emerging evidence has suggested a close correlation between COVID-19 and neurodegenerative disorders. However, whether there exists causal association the effect direction remains unknown. To examine causative role of in risk disorders, we estimated their genetic correlation, then conducted two-sample Mendelian randomization analysis using summary statistics from genome-wide studies susceptibility, hospitalization, severity COVID-19, as well six major disorders including Alzheimer's disease (AD), amyotrophic lateral sclerosis, frontotemporal dementia, Lewy body multiple Parkinson's disease. We identified significant positive hospitalization AD (genetic correlation: 0.23, P = 8.36E-07). Meanwhile, was significantly associated with higher (OR: 1.02, 95% CI: 1.01-1.03, P: 1.19E-03). Consistently, susceptibility 1.05, 1.01-1.09, 9.30E-03) 1.01, 1.00-1.02, 0.012) were nominally AD. The results robust under all sensitivity analyses. These demonstrated that could increase Future development preventive or therapeutic interventions attach importance to this alleviate complications COVID-19.

Язык: Английский

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Microgliosis and neuronal proteinopathy in brain persist beyond viral clearance in SARS-CoV-2 hamster model

EBioMedicine, Год журнала: 2022, Номер 79, С. 103999 - 103999

Опубликована: Апрель 16, 2022

Neurological symptoms such as cognitive decline and depression contribute substantially to post-COVID-19 syndrome, defined lasting several weeks after initial SARS-CoV-2 infection. The pathogenesis is still elusive, which hampers appropriate treatment. Neuroinflammatory responses neurodegenerative processes may occur in absence of overt neuroinvasion.Here we determined whether intranasal infection male female syrian golden hamsters results persistent brain pathology. Brains 3 (symptomatic) or 14 days (viral clearance) post versus mock (n = 10 each) were immunohistochemically analyzed for viral protein, neuroinflammatory response accumulation tau, hyperphosphorylated tau alpha-synuclein protein.Viral protein the nasal cavity led pronounced microglia activation olfactory bulb beyond clearance. Cortical but not hippocampal neurons accumulated alpha-synuclein, inflammation neurodegeneration. Importantly, all regions affected, line with selective vulnerability.Thus, despite virus brain, develop signatures proteinopathies that progressive neuronal dysfunction. Further depth analysis this important mechanism required.Federal Ministry Health (BMG; ZMV I 1-2520COR501), Federal Education Research (BMBF 01KI1723G), Science Culture Lower Saxony Germany (14 - 76103-184 CORONA-15/20), German Foundation (DFG; 398066876/GRK 2485/1), Luxemburgish National Fund (FNR, Project Reference: 15686728, EU SC1-PHE-CORONAVIRUS-2020 MANCO, no > 101003651).

Язык: Английский

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Cellular and molecular biomarkers of long COVID: a scoping review

EBioMedicine, Год журнала: 2023, Номер 91, С. 104552 - 104552

Опубликована: Апрель 8, 2023

Язык: Английский

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The long-term health outcomes, pathophysiological mechanisms and multidisciplinary management of long COVID

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Ноя. 1, 2023

Abstract There have been hundreds of millions cases coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome 2 (SARS-CoV-2). With the growing population recovered patients, it crucial to understand long-term consequences and management strategies. Although COVID-19 was initially considered an illness, recent evidence suggests that manifestations including but not limited those cardiovascular, respiratory, neuropsychiatric, gastrointestinal, reproductive, musculoskeletal systems may persist long after phase. These persistent manifestations, also referred as COVID, could impact all patients with across full spectrum illness severity. Herein, we comprehensively review current literature on highlighting its epidemiological understanding, vaccinations, organ-specific sequelae, pathophysiological mechanisms, multidisciplinary In addition, psychological psychosomatic factors underscored. Despite these findings diagnostic therapeutic strategies based previous experience pilot studies remain inadequate, well-designed clinical trials should be prioritized validate existing hypotheses. Thus, propose primary challenges concerning biological knowledge gaps efficient remedies well discuss corresponding recommendations.

Язык: Английский

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

Journal of Medical Virology, Год журнала: 2023, Номер 95(7)

Опубликована: Июль 1, 2023

Abstract The association between SARS‐CoV‐2 infection with increased risk for new‐onset neurodegenerative diseases remains unclear. Therefore, this meta‐analysis aims to elucidate whether are long‐term sequelae of infection. PubMed/MEDLINE, CENTRAL, and EMBASE were systematically searched articles published up January 10, 2023. A systematic review performed calculate the pooled effect size, expressed as hazard ratios (HR) corresponding 95% confidence interval (CI) each outcome. Twelve studies involving 33 146 809 individuals (2 688 417 post‐COVID‐19 cases 30 458 392 controls) included in present meta‐analysis. analyses compared control groups showed a significant Alzheimer's disease (HR = 1.50, CI 1.22–1.85, I 2 97%), dementia 1.66, 1.42–1.94, 91%), Parkinson's 1.44, 1.06–1.95, 86%) among COVID‐19 survivors. may be associated higher recovered patients. Future warranted determine biological mechanisms underlying consequences

Язык: Английский

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Causal effect of COVID‐19 on Alzheimer's disease: A Mendelian randomization study

Journal of Medical Virology, Год журнала: 2022, Номер 95(1)

Опубликована: Авг. 30, 2022

It was reported that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may cause brain size reduction and cognitive decline. Whether COVID-19 contribute to the development of Alzheimer's disease (AD) is not known. We conducted genetic correlation Mendelian randomization (MR) analyses assess relationships potential causal associations between AD three outcomes (SARS-CoV-2 infection, hospitalization, critical COVID-19) by utilizing genome-wide association study datasets on these traits. A map COVID-19-driven molecular pathways constructed investigate mechanisms underlying connection. Genetic indicated had a significant positive with hospitalized (rg = 0.271). The MR analysis from inverse-variance-weighted model showed liabilities (odds ratio: 1.02, 95% confidence interval: 1.01-1.03) (1.01, 1.00-1.02) were associated an increased risk for AD. However, no effect liability SARS-CoV-2 detected (1.03, 0.97-1.09). total 60 functionally interconnected genes mediate COVID-19-AD connection, which functional enrichment in immunity-related tissue lung brain. Our suggests AD, while suffering mild case increase influence be mediated acting predominantly

Язык: Английский

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Post-COVID-19 Syndrome is Rarely Associated with Damage of the Nervous System: Findings from a Prospective Observational Cohort Study in 171 Patients

Neurology and Therapy, Год журнала: 2022, Номер 11(4), С. 1637 - 1657

Опубликована: Авг. 26, 2022

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect multiple organs. Reports of persistent or newly emergent symptoms, including those related to the nervous system, have increased over course pandemic, leading introduction post-COVID-19 syndrome. However, this novel is still ill-defined and structured objectification complaints scarce. Therefore, we performed a prospective observational cohort study better define validate subjective neurological disturbances in patients with syndrome.A total 171 fulfilling WHO Delphi consensus criteria underwent comprehensive diagnostic work-up neurovascular, electrophysiological, blood analysis. In addition, magnetic resonance imaging (MRI) lumbar puncture were conducted subgroups patients. Furthermore, neuropsychological, psychosomatic, fatigue assessment.Patients predominantly female, middle-aged, had incurred mostly mild-to-moderate COVID-19. most frequent included fatigue, difficulties concentration, memory deficits. (85.8%), in-depth assessment yielded no pathological findings. 97.7% cases, either diagnosis other than post COVID-19 syndrome, likely preceding could be established. Sensory motor more often associated Previous psychiatric conditions identified as risk factor for developing We found high somatization scores our patient group that correlated cognitive deficits extent fatigue.Albeit frequently reported by patients, objectifiable affection system rare Instead, elevated levels point towards pathogenesis potentially involving psychosomatic factors. thorough important order not miss diseases post-COVID-19.

Язык: Английский

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