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Hypothesis: Interleukin-6 as potential mediator of long-term neuropsychiatric symptoms of COVID-19, 2021, Kappelmann et al

Discussion in 'Long Covid research' started by Andy, Jun 16, 2021.

  1. Andy

    Andy Committee Member

    Messages:
    21,956
    Location:
    Hampshire, UK
    Highlights

    • Long COVID symptoms include fatigue, sleeping difficulties, depression and anxiety.
    • These symptoms may arise from effects of interleukin 6 (IL-6) on the brain.
    • Cytokine driven immuno-metabolic constraints on neuronal energy metabolism can cause fatigue.
    • Anti-IL-6 treatment reduces severe complications and mortality in COVID-19 patients.
    • IL-6/IL-6R pathway could be a target for treatment and prevention of long COVID.

    Abstract

    The majority of COVID-19 survivors experience long-term neuropsychiatric symptoms such as fatigue, sleeping difficulties, depression and anxiety. We propose that neuroimmune cross-talk via inflammatory cytokines such as interleukin-6 (IL-6) could underpin these long-term COVID-19 symptoms. This hypothesis is supported by several lines of research, including population-based cohort and genetic Mendelian Randomisation studies suggesting that inflammation is associated with fatigue and sleeping difficulties, and that IL-6 could represent a possible causal driver for these symptoms. Immune activation following COVID-19 can disrupt T helper 17 (TH17) and regulatory T (Treg) cell responses, affect central learning and emotional processes, and lead to a vicious cycle of inflammation and mitochondrial dysfunction that amplifies the inflammatory process and results in immuno-metabolic constraints on neuronal energy metabolism, with fatigue being the ultimate result. Increased cytokine activity drives this process and could be targeted to interrupt it. Therefore, whether persistent IL-6 dysregulation contributes to COVID-19-related long-term fatigue, sleeping difficulties, depression, and anxiety, and whether targeting IL-6 pathways could be helpful for treatment and prevention of long COVID are important questions that require investigation. This line of research could inform new approaches for treatment and prevention of long-term neuropsychiatric symptoms of COVID-19. Effective treatment and prevention of this condition could also help to stem the anticipated rise in depression and other mental illnesses ensuing this pandemic.

    Open access, https://www.sciencedirect.com/science/article/pii/S0306453021001694
     
    Andy, Jun 16, 2021
    #1
    Wyva, Sean, Michelle and 4 others like this.
  2. Hutan

    Hutan Moderator Staff Member

    Messages:
    26,932
    Location:
    Aotearoa New Zealand
    Interesting to track who is getting involved in this type of hypothesising, I think.

    NilsKappelmann a,b; RobertDantzer c; Golam M.Khandaker d,e,f,g
    a Department of Research in Translational Psychiatry, Max-Planck-Institute of Psychiatry, Munich, Germany
    b International Max Planck Research School for Translational Psychiatry (IMPRS-TP), Munich, Germany
    c Department of Symptom Research, University of Texas MD Anderson Cancer Centre, Houston, TX, USA
    d MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
    e Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
    f Department of Psychiatry, University of Cambridge, Cambridge, UK
    g Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK

    That seems a bold statement and unlikely to be true, if 'long-term' means anything like what I assume it to mean (i.e. more than 3 months) and 'depression' and 'anxiety' means substantially more than feeling a bit worried and sad about what the pandemic has done to one's family and community and financial well-being. The authors mention a Wuhan study that found that about 75% of patients still experienced at least one physical or mental health symptom six months after hospitalisation, with fatigue or muscle weakness (63%), sleeping difficulties (26%), and depression or anxiety (23%) being the most common - but these were hospital-discharged patients.


    The authors seem to assume that fatigue and sleeping difficulties means depression. This inability to see fatigue as separate from depression means that their analysis lacks clarity.


    Nevertheless, they do seem to be thinking about Long Covid in biological terms. This was interesting:
     
    Hutan, Jun 17, 2021
    #2
    Tia, alktipping, shak8 and 7 others like this.

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