Cog-fog and fatigue

Case study (n=1 or n = me)I am day 4 into my first bout of COVID-19 and it is no joke. Although I only have a sore throat and mild cold-like symptoms the fatigue and cog-fog are something else. Any physical effort results in tachycardia and a feeling of profound exhaustion. I am having difficulty working, which for me is essential. I had to do two small virtual online clinics and chair an online meeting on EBV and MS, which floored me. My attention and concentration are limited to short bursts of activity, not to mention my memory and recall of simple things. I do the daily Spelling Bee game in the New York Times and usually get to a level of GREAT or AMAZING  and occasionally GENIUS. Since having COVID I can't get past NICE. In addition, I have a thick torpor that is hanging around my head. Some of this may be because I am sleep deprived. Having a cough, chills and night sweats interferes with your sleep. I think I now know what cog-fog feels like.Many patients with MS who have had COVID tell me that the cog-fog and fatigue of COVID and long-COVID are what MS-related cog-fog and fatigue feel like. If this is the case I now have a greater appreciation for what it must be like to live with MS. PathogenesisMoving onto the pathogenesis; could MS- and COVID-19-related cog-fog be due to the same mechanisms? I suspect yes. A large number of studies have now documented the nature and frequency of long COVID symptoms. Within the cognitive domain, as many as one in four people with long-COVID experience cog-fog, which includes problems in attention, language fluency, processing speed, executive function, and memory. You may notice these are the same problems that affect pwMS. A recent animal model of mild COVID-19 (see paper 1 below) shows that systemic infection with SARS-CoV-2 leads to CNS inflammation, which includes cytokine-induced activation of microglia, causing decreased hippocampal neurogenesis and a loss of myelinated subcortical axons. I have little doubt that these same problems are occurring in the brains of pwMS.This syndrome of systemic inflammation causing profound fatigue and cog-fog is not new. Most pwMS who have a systemic infection are hit very hard and it takes them weeks to months to get back to some kind of normal. I have even noticed that some patients with more advanced MS don’t get back to their original baseline, in other words, they take a permanent hit from systemic infections. This is why as part of the holistic management of MS we need to treat and prevent systemic infections aggressively. It has also been suggested that chemo-brain is due to similar mechanisms, i.e. chemotherapy triggers CNS inflammation, which causes cog-fog. This may explain why patients with more advanced or progressive MS tolerate AHSCT so poorly. The overlap between COVID-19 and MS-related cog-fog beggars the question of whether both are due to viral infections. This is why the recent description that two-thirds of patients with long-COVID had evidence of recent EBV reactivation is so interesting (see paper 2 below). The paper suggests that infections with SARS-CoV-2 trigger EBV reactivation and it may be the EBV that is causing the problem and not the SARS-CoV-2 itself. This is important as chronic EBV infection is associated, in some cases, with chronic fatigue syndrome. As you are aware the association between EBV and MS is now likely to be causal and one hypothesis states that continued EBV infection, i.e. cycling between latent and lytic infection, is driving MS disease activity. This is the reason why we are pushing so hard to test antiviral therapies targeting EBV in MS. Just maybe we should be testing these antiviral agents in patients with long-COVID as well. Please note that MS-related fatigue is complicated and if you do have a problem with it you need to see your HCP and have a full work-up as many of the factors underpinning MS-related fatigue are treatable. I have done a previous MS-selfie newsletter on this issue; I would urge you to read it (Why am I so fatigued? 9-Aug-2021). Another newsletter of interest concerns ‘Cog-Fog and Sickness Behaviour’ in pwMS (19-Oct-2021). I would be interested to hear if any of you have long-COVID and how the associated fatigue and cog-fog compares to that due to MS itself. In addition, have any of you found any successful strategies to help cope with these symptoms? Thank you. Paper 1Fernández-Castañeda  et al. Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation. Cell. 2022 Jun 13;185(14):2452-2468.e16.COVID survivors frequently experience lingering neurological symptoms that resemble cancer-therapy-related cognitive impairment, a syndrome for which white matter microglial reactivity and consequent neural dysregulation is central. Here, we explored the neurobiological effects of respiratory SARS-CoV-2 infection and found white-matter-selective microglial reactivity in mice and humans. Following mild respiratory COVID in mice, persistently impaired hippocampal neurogenesis, decreased oligodendrocytes, and myelin loss were evident together with elevated CSF cytokines/chemokines including CCL11. Systemic CCL11 administration specifically caused hippocampal microglial reactivity and impaired neurogenesis. Concordantly, humans with lasting cognitive symptoms post-COVID exhibit elevated CCL11 levels. Compared with SARS-CoV-2, mild respiratory influenza in mice caused similar patterns of white-matter-selective microglial reactivity, oligodendrocyte loss, impaired neurogenesis, and elevated CCL11 at early time points, but after influenza, only elevated CCL11 and hippocampal pathology persisted. These findings illustrate similar neuropathophysiology after cancer therapy and respiratory SARS-CoV-2 infection which may contribute to cognitive impairment following even mild COVID.Paper 2Gold et al. Investigation of Long COVID Prevalence and Its Relationship to Epstein-Barr Virus Reactivation. Pathogens. 2021 Jun 17;10(6):763.Coronavirus disease 2019 (COVID-19) patients sometimes experience long-term symptoms following resolution of acute disease, including fatigue, brain fog, and rashes. Collectively these have become known as long COVID. Our aim was to first determine long COVID prevalence in 185 randomly surveyed COVID-19 patients and, subsequently, to determine if there was an association between occurrence of long COVID symptoms and reactivation of Epstein-Barr virus (EBV) in 68 COVID-19 patients recruited from those surveyed. We found the prevalence of long COVID symptoms to be 30.3% (56/185), which included 4 initially asymptomatic COVID-19 patients who later developed long COVID symptoms. Next, we found that 66.7% (20/30) of long COVID subjects versus 10% (2/20) of control subjects in our primary study group were positive for EBV reactivation based on positive titers for EBV early antigen-diffuse (EA-D) IgG or EBV viral capsid antigen (VCA) IgM. The difference was significant (p Subscriptions and donationsPaid subscriptions to MS-Selfie are being used to administer the Newsletter and associated MS-Selfie microsite that is currently in development. 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