Increased Risk of Long Covid in Trans Populations
Recent census data from the US suggests that transgender people are 3 times more likely to experience long covid than cisgender men (Centers for Disease Control and Prevention, 2022).
Long covid is a group of symptoms occurring for at least 2 months post covid infection which haven’t been attributed to another cause. These symptoms can include:
Fatigue
Chest pain/tightness
Shortness of breath
Reduced exercise capacity
Heart palpitations
Digestive symptoms
Pain or pins and needles
Anxiety
Depression
Headache
Brain fog
Dizziness on standing
Joint or muscle pain
Rash
Trouble sleeping
Those with underlying health conditions and/or with more severe covid 19 are at higher risk of developing long covid. (Centers for Disease Control and Prevention, 2022)
So why might long covid be more common amongst trans people?
A likely culprit is health inequity.
Trans people are more likely to experience chronic disease due to a lack of access to non-discriminatory health care services and higher rates of mental health concerns. A 2021 survey in Australia showed that almost ¾ of trans people aged 14 to 25 reported being diagnosed with anxiety (LGBTIQ+ Health Australia, 2021). These statistics are a result of discrimination (including social, health care, housing and employment discrimination) and lead to poorer physical health outcomes.
How does long covid fit with pre-existing ideas around post-viral illness?
Long covid is not a new phenomenon. We see this with other viral infections, most notably Epstein B virus (EBV) resulting in chronic fatigue syndrome (CFS) or fibromyalgia. These conditions share many similarities with long covid symptoms.
The roles of chronic infection and inflammation in the development of post viral illness are well unified by researcher Robert Naviaux who termed the concept the Cell Danger Response (CDR) (a concept with many ties to polyvagal theory). This theory posits that chronic activation of the CDR results in a hypometabolic state similar to that seem in the worm c. elegans in its “daeur” state after exposure to stress. The theory explains how a number of triggers including viral infections (EBV, ross river virus, covid19), traumatic injuries and toxic exposures can trigger post viral conditions like CFS, fibromyalgia and long covid.
The CDR is a mitochondria-centric theory, with changes to mitochondrial function appearing key to the development of symptoms.
Mitochondria = the machinery inside our cells which churns out energy in the form of ATP.
Mitochondria not only act to create energy, but act as sensors of environmental threats. This includes infection, toxic exposure and physical or psychological trauma (yet another tie between the systems of oppression which effect our psyche and physical health outcomes). In response to threat they swap from prioritising energy production to sending out danger signalling molecules to surrounding cells. Under chronic stress/threat this danger response can be difficult to switch off, leading to symptoms including chronic fatigue.
(Naviauxet al., 2014; Naviauxet al., 2016; Naviaux, 2019)
Fortunately naturopaths have acknowledged the existence of these conditions for decades and have tools to support those struggling with post-viral conditions.
For one on one support make a booking at www.gut-logic.com/book-online
A more complex look at the CDR for practitioners & huge nerds:
Viral infection activates the CDR, which switches mitochondrial function from energy making to oxidative shielding which includes the production of ROS and other anti-viral and anti-microbial chemicals. ATP is pumped out of the cell by mitochondria to be utilised as a danger signalling molecule known as a “mitokine.”
In the CNS, extracellular ATP activates an immune response by microglia which produces inflammatory mediators, ROS and excessive lactate generation via anaerobic glycolysis. This is a less efficient energy synthesis pathway implicated in low-grade neuro-inflammation and CNS fatigue. (Mueller et al., 2019)
This immune response also stimulates IL-1β secretion by microglia and macrophages which upregulates serotonin transport into astrocytes. When taken up by astrocytes, serotonin undergoes deamination resulting in reduced extracellular levels. The subsequent reduction in stimulation of the 5HT-1A receptor induces fatigue. Reduced extracellular 5-HT levels are also implicated in mood disorders and insomnia due to decreased melatonin synthesis (Noda et al., 2018).
Other key metabolic pathways altered in the CDR can explain symptoms of chronic fatigue and fibromyalgia. These include altered methylation, sphingolipid and phospholipid abnormalities, altered metabolism of tryptophan, NAD+, B vitamins and vitamin D, and microbiome changes. (Naviaux, 2014)
Methylation is reduced in order to favour construction of antimicrobial and antiviral compounds. SAMe is utilised for polyamine synthesis to create hydrogen peroxide and antimicrobial polyamine aldehydes. This decreases the SAMe/SAH ratio while also decreasing the availability of SAMe for DNA methylation resulting in impaired neurotransmitter methylation reactions and symptoms of anxiety. The cell is purposefully reducing the SAMe/SAH ratio to prevent invading pathogens utilising SAMe as a methyl donor for their own mRNA maturation, and therefore preventing pathogen replication. (Naviaux, 2014)
Sphingolipid abnormalities involve the creation of sphingosine 1-phosphate from sphingosine, versus sphingomyelin creation. Sphingosine 1-phosphate is involved in destruction of intracellular parasites, stimulates mTOR and Th1 immune cells and inhibits Treg cells. Chronically decreased sphingomyelin is particularly common in males with CFS and reflects a chronic stimulation of the innate immune system. (Naviaux, 2014)
Phospholipid abnormalities include the replacement of short polyunsaturated lipids to long chain saturated lipids in cellular membranes to form a rigid barrier preventing cellular invasion and Phospholipase D2 is also translocated to the cell membrane which activates G-protein coupled receptors involved in purinergic signalling and the innate immune response. (Naviaux, 2014)
Tryptophan metabolism is altered during the CDR from the hydroxylation pathway, which creates serotonin and melatonin, to the dioxygenase pathway which creates kynurenine which is implicated in anxiety and stimulates innate immune function increasing IL-6 production. (Naviaux, 2014)
B6 is utilised throughout this dioxygenase pathway, lowering systemic pyridoxal 5’-phophate which is required for deactivation of aspects of the innate immune response (e.g. enzymatic de-activation of lymphocyte chemoattractant sphingosine-1 phosphate), prolonging the cell danger response. (Naviaux, 2014)
Reduced systemic P5P inhibits GABA production, resulting in elevated glutamate and symptoms of anxiety, hyperalgesia and insomnia. The enzyme glutamate decarboxylase which converts glutamate to GABA requires P5P as a co-factor. Significantly elevated glutamine and decreased GABA is commonly observed in CFS and fibromyalgia patients. (Fitzgerald & Carter, 2011; Foerster et al., 2012; Harris et al., 2009; Lee et al., 2019; Pyke et al., 2017)
Vitamin D metabolism is altered due to upregulation of mitochondrial enzyme 24α-hydroxylase which breaks down vitamin D. Vitamin D deficiency is implicated in CFS/FM immune dysregulation. This enzyme is further downregulated by gut derived endotoxin, which is commonly elevated in CFS patients with IBS-type symptoms. (Naviaux, 2014)
Microbiome and intestinal epithelial dysfunction resulting in gluten sensitivity is common to CFS and fibromyalgia. The CDR model proposes that oxidative stress induces dysbiosis and intestinal epithelial cell dysfunction resulting in altered uptake, processing and folding of gliadin peptides and subsequent gluten sensitivity. (Naviaux et al., 2016)
#transhealth #sam_naturopath #gutlogic #perthnaturopath #longcovid #chronicfatigue #fibromyalgia #postviralfatigue #covid19
References:
Centers for Disease Control and Prevention. (2022). Long COVID or Post-COVID Conditions Post-COVID Conditions. https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects/index.html
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LGBTIQ+ Health Australia. (2021). Snapshot of Mental Health and Suicide Prevention Statistics for LGBTI People (Issue April). https://www.lgbtiqhealth.org.au/about
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