Covid-19 and Long-Haulers

Impaired OB Neurogenesis

Overview

  • Presenter: Abdallah HAYAR

  • Institution: Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences

  • Focus Area: Exploring the connections between COVID-19, brain health, and neurological impacts, particularly in relation to the olfactory bulb (OB) neurogenesis.

COVID-19 and the Brain

  • Key Themes:
      - Healthy Brain vs. COVID-19 Brain
      - Impairments in neurogenesis
      - Potential effects on dopaminergic neurons due to COVID-19.

Main Topics Covered in the Study

  1. Organs Affected by COVID-19:
       - Overview of how COVID-19 impacts various organ systems and the brain.

  2. Symptoms of Long COVID-19:
       - Description of long-term symptoms including neurological effects, brain fog, depression, and cognitive dysfunction.

  3. Brain Damage Mechanisms:
       - Discussion on why brain damage is likely responsible for long COVID symptoms.

  4. Evidence of COVID-19 Related Brain Damage:
       - Overview of studies providing evidence for neuroinflammation and changes in neuroplasticity associated with COVID-19.

  5. Comparison with Neurodegenerative Diseases:
       - How COVID-19 may mimic or contribute to conditions such as Parkinson's disease, Alzheimer's disease.

  6. ACE2 Receptor Involvement:
       - Location and role of ACE2 receptors in various organs, including the brain, typically associated with COVID-19.

  7. Routes of Virus Entry into the Brain:
       - Detailed discussion on potential pathways through which SARS-CoV-2 may enter the central nervous system (CNS).

  8. Animal Models and Human Organoids:
       - Utilization of model organisms and 3D human brain organoids to study the effects of COVID-19 on neurological health and neurogenesis.

  9. Vaccine Efficacy:
       - Analysis of vaccines as a preventive measure against neurological impacts of COVID-19 and reasons behind vaccine hesitancy.

COVID-19 Symptoms Across Organs

  • Systemic Symptoms:
      - Common symptoms: Coughing, sneezing, difficulty breathing, pneumonia.   - Severe symptoms: Severe acute respiratory syndrome (SARS) and acute respiratory distress syndrome (ARDS).   - Cardiovascular effects: Cardiac injury and elevated levels of troponin.   - Renal effects: Proteinuria, hematuria, and acute kidney injury.   - Hepatic injuries: Elevated ALT and AST levels often lead to hepatic damage.

  • Co-morbidities:
      - Conditions that may exacerbate COVID-19: Diabetes mellitus, Hypertension, Cancer, Tuberculosis.   - Symptoms affecting eyes: Conjunctivitis, epiphora, increased secretions.   - Gastrointestinal symptoms: Nausea, vomiting, abdominal pain, diarrhea.

Neurogenesis: Healing and Recovery

  • Challenges in Brain Healing:
      - Unlike skin, neurons have limited capacity for regeneration; they do not divide effectively.   - Immune response varies; brain's immune cells may cause further damage by remaining overactivated.   - Synaptic plasticity allows for adaptation and connection reformation between healthy neurons.

Long-Hauler Neurological Symptoms

  • Potential Causes:
      - Neurodegeneration and/or low-grade inflammation as contributing factors.

  • Prognosis:
      - Outcomes linked to cellular degeneration tend to be poor.
      - Therapy for inflammatory-based symptoms could lead to better prognoses.

  • Public Perspective:
      - Mention of emotional and psychological impact, including depression and cognitive fog attributed to COVID-19.

Predictors of Post-COVID-19 Syndrome

  • Occurrence of post-COVID syndrome, even post-mild infection, is noted (Shah et al. 2021).   - Symptoms include fatigue, anosmia (loss of smell), ageusia (loss of taste), and shortness of breath lasting beyond 4 to 7 months.   - Increased incidence among females; lower serum IgG titers are noted as a correlation with persistent symptoms.   - Mention of cohort studies indicating that 11% of patients could not fully participate in regular life after seven months (Augustin et al. 2021).

Brain Imaging Evidence

  • Brain Changes Pre-and Post-COVID-19 (Douaud et al. 2021):
      - Reduction in grey matter thickness observed in key brain areas (lateral orbitofrontal cortex, parahippocampal gyrus).   - Evidence of tissue damage indicated by increased diffusion indices associated with olfactory connections.   - Increased cerebrospinal fluid volume suggesting diffuse brain atrophy post COVID-19 infection.

Neurological Response Patterns

  • PET Imaging Results (Guedj et al. 2021):
      - Participants exhibited hypometabolism in critical brain regions related to COVID-19 effects after infection.   - Neuroimaging correlated with functional complaints and age-related responses indicating younger patients with memory impairments.

Gene Expression Changes

  • Examination of synaptic deficits associated with COVID-19, especially in excitatory neurons and specific interneurons correlating to long-term symptoms (Yang et al. 2021).   - Changes resembling those in chronic brain disorders, emphasizing potential therapeutic avenues.

Risk for Parkinson's Disease Post-COVID-19

  • Evidence (Brundin et al. 2020) suggests that COVID-19 pathways (vascular damage, systemic inflammation, neuroinvasion) align with observed brain changes common in Parkinson’s Disease.

Viral Mechanisms and Entry Points

  • Receptor Usage and Intrusion:
      - Different coronaviruses utilize various receptors for binding, with SARS-CoV-2 favoring ACE2 for entry into cells.   - Chronic changes in receptor expression may influence susceptibility to severe disease and propagate CNS viral infiltration.

Cellular Responses to COVID-19

  • Low ACE2 expression in brain contrast to higher expression in organs like the heart, gut, and lungs could dictate broader implications for COVID-19 morbidity outcomes (Li et al. 2020).

Epigenetic Factors in COVID-19 Severity

  • Susceptibility Related Correlations:
      - Hypomethylation patterns present in vulnerable populations such as older adults and smokers.   - Methylation and genetic variations seen in ACE2 participation indicate distinct immune responses and severity.

COVID-19 Effects on Olfactory Bulb and Neuroinvasion

  • Detailed exploration of ACE2's role in olfactory regions and the neurological implications of its expression (Hernández et al. 2021).

Neuroinvasion Pathways

  • In-depth discussion on transcribral routes allowing SARS-CoV-2 access to the CNS, particularly through olfactory neuronal pathways (Jafari Khaljiri et al. 2021).

Clinical Outcomes and Olfactory Dysfunction

  • Studies indicating the prevalence of anosmia post-COVID-19 and associated recovery rates over time, considering both subjective and objective assessments (Renaud et al. 2021; Teaima et al. 2021).

Inflammatory Responses and Neuropathology

  • Discussion of the potential for SARS-CoV-2 to prompt microglia activation, macrophage recruitment, and excitotoxicity, leading to neuropsychiatric symptoms (Han et al. 2021).

Vaccine Development and Efficacy

  • Explanation of mRNA vaccine mechanisms and their role in stimulating the immune response against COVID-19.

Vaccine Hesitancy

  • Addressing misinformation and fears rooted in conspiracy theories while emphasizing the relative safety of vaccines compared to COVID-19 risks.

Recommendations for Olfactory Training

  • Suggested regimen using familiar and pleasant odorants for olfactory dysfunction rehabilitation post-COVID-19 (Hummel et al. 2009).   - Recovery rates linked to continuous olfactory training have shown improvement; observational studies support these findings.

Implications of neurogenesis and neuroplasticity

  • Importance of neuroplasticity in recovering from COVID-19 related neurological damage.
      - Lifestyle adjustments such as exercise and exposure to sunlight may improve symptoms related to COVID-induced brain changes.