The underlying sex differences in neuroendocrine adaptations relevant to Myalgic Encephalomyelitis Chronic Fatigue Syndrome

Thomas, Natalie; Gurvich, Caroline; Huang, Katherine; Gooley, Paul R.; Armstrong, Christopher W.

doi:10.1016/j.yfrne.2022.100995

Cited by 28 publications

(21 citation statements)

References 89 publications

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“…It should be noted that LC symptoms have a significant overlap with those found in other PAIS conditions 5 . These findings provide support to investigate the role of sex hormones in PAIS including ME/CFS and chronic Lyme disease 11,34–37 .…”

Section: Discussionsupporting

confidence: 67%

“…LC shares many traits with other post-acute infection syndromes (PAIS) which have been described following many infectious illnesses 5 , including fatigue, post-exertional malaise, pain, and neurocognitive symptoms, with many symptoms showing a strong female sex bias 11 . Unlike acute COVID-19, where males face higher severity and mortality [12][13][14][15] , LC has shown a strong repeated female bias in both the rate of diagnosis and symptomology, with females experiencing higher rates of headaches and neurological conditions, and males showing endocrine dysfunction 1,3 .…”

Section: Introductionmentioning

confidence: 99%

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Sex differences in symptomatology and immune profiles of Long COVID

Silva,

Takahashi,

Wood

et al. 2024

Preprint

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SummaryStrong sex differences in the frequencies and manifestations of Long COVID (LC) have been reported with females significantly more likely than males to present with LC after acute SARS-CoV-2 infection1–7. However, whether immunological traits underlying LC differ between sexes, and whether such differences explain the differential manifestations of LC symptomology is currently unknown. Here, we performed sex-based multi-dimensional immune-endocrine profiling of 165 individuals8with and without LC in an exploratory, cross-sectional study to identify key immunological traits underlying biological sex differences in LC. We found that female and male participants with LC experienced different sets of symptoms, and distinct patterns of organ system involvement, with female participants suffering from a higher symptom burden. Machine learning approaches identified differential sets of immune features that characterized LC in females and males. Males with LC had decreased frequencies of monocyte and DC populations, elevated NK cells, and plasma cytokines including IL-8 and TGF-β-family members. Females with LC had increased frequencies of exhausted T cells, cytokine-secreting T cells, higher antibody reactivity to latent herpes viruses including EBV, HSV-2, and CMV, and lower testosterone levels than their control female counterparts. Testosterone levels were significantly associated with lower symptom burden in LC participants over sex designation. These findings suggest distinct immunological processes of LC in females and males and illuminate the crucial role of immune-endocrine dysregulation in sex-specific pathology.

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Section: Discussionsupporting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Sex differences in symptomatology and immune profiles of Long COVID

Silva,

Takahashi,

Wood

et al. 2024

Preprint

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“…Research on ME/CFS shows associations between ME/CFS and premenstrual dysphoric disorder, polycystic ovarian syndrome, menstrual cycle abnormalities, ovarian cysts, early menopause and endometriosis [128][129][130] . Pregnancy, postpartum changes, perimenopause and menstrual cycle fluctuations affect ME/CFS and influence metabolic and immune system changes 129 . Long COVID research should focus on these relationships to better understand the pathophysiology.…”

Section: Reproductive Systemmentioning

confidence: 99%

Long COVID: major findings, mechanisms and recommendations

Davis¹,

McCorkell²,

et al. 2023

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Long COVID is an often debilitating illness that occurs in at least 10% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. More than 200 symptoms have been identified with impacts on multiple organ systems. At least 65 million individuals worldwide are estimated to have long COVID, with cases increasing daily. Biomedical research has made substantial progress in identifying various pathophysiological changes and risk factors and in characterizing the illness; further, similarities with other viral-onset illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome have laid the groundwork for research in the field. In this Review, we explore the current literature and highlight key findings, the overlap with other conditions, the variable onset of symptoms, long COVID in children and the impact of vaccinations. Although these key findings are critical to understanding long COVID, current diagnostic and treatment options are insufficient, and clinical trials must be prioritized that address leading hypotheses. Additionally, to strengthen long COVID research, future studies must account for biases and SARS-CoV-2 testing issues, build on viral-onset research, be inclusive of marginalized populations and meaningfully engage patients throughout the research process.

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“…With an estimated prevalence of 0.1%-0.7%, CFS/ ME is far above the threshold value set by the European Union for classification as a rare disease (<5:10 000). [19][20][21] In Germany, its prevalence was comparable with multiple sclerosis (MS, ~300 000) before the COVID-19 pandemic. 18 CFS/ME is also associated with a considerable burden of disease.…”

Section: E D I T O R I a L E X A C T Amentioning

confidence: 99%

“…Interestingly, the innate immune response to infections is generally higher among women than men, which could perhaps also explain the higher prevalence of CFS/ME among women given the role that immunity plays in it. With an estimated prevalence of 0.1%–0.7%, CFS/ME is far above the threshold value set by the European Union for classification as a rare disease (<5:10 000) 19–21 . In Germany, its prevalence was comparable with multiple sclerosis (MS, ~300 000) before the COVID‐19 pandemic 18 .…”

mentioning

confidence: 98%