Tag: women vs men

Sex and disease severity-based analysis of steroid hormones in ME/CFS

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating disease characterized by decreased daily activity and persistent fatigue after physical and/or cognitive exertion. Although ME/CFS affects both sexes, there is a higher preponderance of cases in women. However, endocrinological studies focused on evaluating this sex-related disparity are limited.

In this scenario, the aim of this study was to measure 9 circulating steroid hormones (SHs) divided into mineralocorticoids (aldosterone), glucocorticoids (cortisol, corticosterone, 11-deoxycortisol, cortisone), androgens (androstenedione, testosterone), and progestins (progesterone, 17α-hydroxyprogesterone) in plasma samples from mild/moderate (ME/CFSmm; females, n=20; males, n=8), severely affected patients (ME/CFSsa; females, n=24; males, n=6), and healthy controls (HC, females, n=12; males, n=17) using ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS).

After correction for multiple testing, we observed that circulating levels of 11-deoxycortisol, 17α-hydroxyprogesterone in females, and progesterone in males were significantly different between HC, ME/CFSmm and ME/CFSsa. Comparing two independent groups, we found that female ME/CFSsa had higher levels of 11-deoxycortisol (vs. HC and ME/CFSmm) and 17α-hydroxyprogesterone (vs. HC).

In addition, female ME/CFSmm showed a significant increase in progesterone levels relative to HC. In contrast, we observed that male ME/CFSmm had lower circulating levels of cortisol and corticosterone, while progesterone levels were elevated compared to HC. In addition to these univariate analyses, our correlational and multivariate approaches identified differential associations between our study groups. Also, using two-component partial least squares discriminant analysis (PLS-DA), we were able to discriminate ME/CFS from HC with an accuracy of 0.712 and 0.846 for females and males, respectively.

In conclusion, our findings not only suggest the potential value of including SHs in future studies aimed at improving stratification in ME/CFS, but also provide new perspectives to explore the clinical relevance of these SH-related differences within specific patient subgroups.

Source: Cornelia Pipper, Linda Bliem, Luis León et al. Sex and disease severity-based analysis of steroid hormones in ME/CFS, 13 October 2023, PREPRINT (Version 1) available at Research Square [https://doi.org/10.21203/rs.3.rs-3428946/v1] https://www.researchsquare.com/article/rs-3428946/v1 (Full text)

Investigating the Effect of COVID-19 Infection on Professional Athletes’ Post-infection With a Focus on Fatigue and Chronic Fatigue Syndrome

Abstract:

Introduction and objectives: COVID-19 has been reported to cause long-term sequela including persistent fatigue and Chronic Fatigue Syndrome (CFS) in the general population. However, it remains to be seen if similar effects are observed in an athlete population. The aetiology and pathophysiology are poorly understood but is thought to be multi-factorial. Patient reported outcome measures are commonly used to improve patient-centred outcomes (PROMs). They are essential to assess patient quality of life post-COVID infection. This paper aims to assess the effect of COVID-19 on athletes’ long-term fatigue and CFS and identify the PROMs used to characterise this.

Methodology: Articles were selected for extraction based on the eligibility criteria and PRISMA guidelines. The inclusion criteria required papers to assess competitive athletes over eighteen years of age who were clinically diagnosed with COVID-19. Articles were extracted to assess different variables including type of sport, type of athlete and ethnicity. Key terms were obtained using MeSH trees and utilised with Web of Science and NCBI Pubmed. Papers were graded by quality using the Hawker quality assessment tool.

Results and discussion: Forty articles (N=40) were identified for full-text screening (N=8). Eight were selected for extraction based on the eligibility criteria. Data was obtained on athlete characteristics, sport characteristics, properties of PROM measurement techniques and fatigue presentation. Male athletes were found to be 10-50% more likely than female athletes to suffer from persistent fatigue symptoms (N=2). Persistent fatigue was present in 9-10% Athletes from mixed backgrounds and genders (N=2). Initial fatigue was documented to be between 47-56% (N=2). A heterogenous range of PROMs were utilised to assess symptoms including fatigue and excluded emotional or mental fatigue.

Conclusion: COVID-19 is associated with signs of persisting fatigue and potentially CFS in athlete populations. More work needs to be done to develop standardised and validated PROMs specific to CFS.

Source: Sarwary, Reza and Tareen, Manahil and Hocaoglu, Mevhibe, Investigating the Effect of COVID-19 Infection on Professional Athletes’ Post-infection With a Focus on Fatigue and Chronic Fatigue Syndrome (January 16, 2023). Available at SSRN: https://ssrn.com/abstract=4573649 or http://dx.doi.org/10.2139/ssrn.4573649 (Full text available as PDF file)

Sex-Dependent Transcriptional Changes in Response to Stress in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Pilot Project

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multi-symptom illness characterized by debilitating fatigue and post-exertional malaise (PEM). Numerous studies have reported sex differences at the epidemiological, cellular, and molecular levels between male and female ME/CFS patients. To gain further insight into these sex-dependent changes, we evaluated differential gene expression by RNA-sequencing (RNA-Seq) in 33 ME/CFS patients (20 female, 13 male) and 34 matched healthy controls (20 female and 14 male) before, during, and after an exercise challenge intended to provoke PEM.
Our findings revealed that pathways related to immune-cell signaling (including IL-12) and natural killer cell cytotoxicity were activated as a result of exertion in the male ME/CFS cohort, while female ME/CFS patients did not show significant enough changes in gene expression to meet the criteria for the differential expression. Functional analysis during recovery from an exercise challenge showed that male ME/CFS patients had distinct changes in the regulation of specific cytokine signals (including IL-1β). Meanwhile, female ME/CFS patients had significant alterations in gene networks related to cell stress, response to herpes viruses, and NF-κβ signaling. The functional pathways and differentially expressed genes highlighted in this pilot project provide insight into the sex-specific pathophysiology of ME/CFS.
Source: Gamer J, Van Booven DJ, Zarnowski O, Arango S, Elias M, Kurian A, Joseph A, Perez M, Collado F, Klimas N, et al. Sex-Dependent Transcriptional Changes in Response to Stress in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Pilot Project. International Journal of Molecular Sciences. 2023; 24(12):10255. https://doi.org/10.3390/ijms241210255 https://www.mdpi.com/1422-0067/24/12/10255 (Full text)

Typing myalgic encephalomyelitis by infection at onset: A DecodeME study

Abstract:

Background: People with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) daily experience core symptoms of post-exertional malaise, unrefreshing sleep, and cognitive impairment or brain fog. Despite numbering 0.2-0.4% of the population, no laboratory test is available for their diagnosis, no effective therapy exists for their treatment, and no scientific breakthrough regarding their pathogenesis has been made. It remains unknown, despite decades of small-scale studies, whether individuals experience different types of ME/CFS separated by onset-type, sex or age.

Methods: DecodeME is a large population-based study of ME/CFS that recruited 17,074 participants in the first 3 months following full launch. Their detailed questionnaire responses provided an unparalleled opportunity to investigate illness severity, onset, course and duration.

Results: The well-established sex-bias among ME/CFS patients is evident in the initial DecodeME cohort: 83.5% of participants were females. What was not known previously was that females’ comorbidities and symptoms tend to be more numerous than males’. Moreover, being female, being older and being over 10 years from ME/CFS onset are significantly associated with greater severity.  Five different ME/CFS onset types were examined in the self-reported data: those with ME/CFS onset (i) after glandular fever (infectious mononucleosis); (ii) after COVID-19 infection; (iii) after other infections; (iv) without an identified infectious onset; and, (v) where the occurrence of an infection at or preceding onset is not known.

Conclusions: This revealed that people with a ME/CFS diagnosis are not a homogeneous group, as clear differences exist in symptomatology and comorbidity.

Source: Bretherick AD, McGrath SJ, Devereux-Cooke A et al. Typing myalgic encephalomyelitis by infection at onset: A DecodeME study [version 1; peer review: awaiting peer review]. NIHR Open Res 2023, 3:20 https://doi.org/10.3310/nihropenres.13421.1 (Full text)

Prevalence and Characterization of Long Covid-19 Symptoms in Health Care Professionals- A Need of the Hour

Abstract:

Background: With the global advent of Covid-19, Healthcare workers (HCW) were under a lot of physical and psychological pressure. Information on persistent symptoms post Covid-19 Infection in HCWs is lacking.

Objectives: This Study is aimed at assessing the impact of the post Covid-19 syndrome in HCWs.

Materials and Methods: A Questionnaire was prepared as google form and shared with the HCWs through WhatsApp enquiring regarding the health conditions that are still persistent post recovery from Covid-19 infection.

Results: A total of 328 Health Care Professionals participated in the present survey (18-65 yrs). The gender distribution revealed 67.7% were females and 32.3% were males. 60.3% of the participants were infected with COVID-19 before taking the first dose of vaccination which is reduced to 17.5% after vaccination. The post COVID complications observed from the study were hair loss (35.4%), easy fatigability (25%), mood swings (22.9%), anxiety (18.8%), insomnia/sleeplessness (13.9%), depression (12.5%) and joint pains/arthritis (11.8%). The other complications observed were loss of taste (9%), lightheadedness/postural hypotension (8.3%), amnesia/loss of memory and anosmia/loss of smell (7.6%), gastritis (6.3%), palpitations, hypersomnia and pulmonary complications (5.6%) and chest pain (4.9%). Unpaired t-test and One-Way ANNOVA resulted in a significant value (p values of >0.05).

Discussion: Despite the fact that females experienced more post-Covid-19 symptoms (15 out of 17), males experienced more chest pain and anxiety symptoms. According to our findings, 57 of 100 Covid-19 health care workers have post-Covid complications. The participants presented with non-specific symptoms such as easy fatigability, mood swings, light headedness, anxiety but most of the participants quoted more specific symptoms such as depression, pulmonary complications, hair loss, joint pains, gastritis, chest pain, palpitations, loss of taste, amnesia, hyperglycemia, insomnia, hypersomnia and anosmia. However, non-specific symptoms such as fatigue, mood swings, lightheadedness, and anxiety were also mentioned. The symptoms of post-acute COVID-19 syndrome vary greatly. Early detection requires a unified definition of long COVID and characterization of its manifestation. Furthermore, more research should be conducted to identify risk factors and the precise mechanisms that lead to the development of long COVID syndrome. Such knowledge may aid future research aimed at preventing such a complication.

Source: Mote Srinath, Syeda Fakiha Mehreen, Surya Prem Kumar et al. Prevalence and Characterization of Long Covid-19 Symptoms in Health Care Professionals- A Need of the Hour, 05 April 2023, PREPRINT (Version 1) available at Research Square. https://doi.org/10.21203/rs.3.rs-2764197/v1 (Full text)

Coronavirus (COVID-19) Pandemic – A Comprehensive Review of Demographics, Comorbidities, Vaccines, Therapeutic Development, Blood Type, and Long Covid

Abstract:

The study summarizes the pandemic COVID-19’s impact on symptoms, demographics, comorbidities, and vaccine and therapeutic development and demonstrates an association with cases and mortality for the past two years. There has been rapid scientific advancement over the past two years 2020-2022 in developing vaccines and therapeutics for combating the disease. We chose three highly affected countries US, India, and China, to address the impact of demographics and comorbidities on COVID-19 using US Center for Disease Control and Prevention (CDC) data.

Based on the analysis of this data, we see that the infection rate is higher in females, while the percentage of death is higher in males than females (p < 0.0001), and the number of female cases among females has increased by 1.7% while the number of deaths among females has decreased by ~1%, within the last two years. The trend of getting affected byCOVID-19 is similar during 2020-2022, i.e., Whites followed by Hispanics and Black people.

After a thorough review of many manuscripts, we concluded that diseases like cardiovascular disease (CVD), diabetes, hypertension, chronic pulmonary obstructive disease (COPD), and acute respiratory distress syndrome (ARDS) were the typical comorbidities leading to severe COVID-19 conditions. In addition, variants of COVID-19, current vaccine and therapeutic development efforts, and relation of COVID-19 with blood type are discussed.

Finally, to conclude that for designing vaccine trials, following FDA’s guidance emphasizing stratification factors based on demographics and comorbidities should be considered while allocating treatment to patients.

Source: Bhattacharyya, Arinjita & Seth, Anand & Rai, Shesh. (2023). Coronavirus (COVID-19) Pandemic -A Comprehensive Review of Demographics, Comorbidities, Vaccines, Therapeutic Development, Blood Type, and Long Covid. 10.36959/856/540.  https://www.researchgate.net/profile/Arinjita_Bhattacharyya/publication/369579104_Coronavirus_COVID-19_Pandemic_-A_Comprehensive_Review_of_Demographics_Comorbidities_Vaccines_Therapeutic_Development_Blood_Type_and_Long_Covid/links/6423001ba1b72772e4318d7d/Coronavirus-COVID-19-Pandemic-A-Comprehensive-Review-of-Demographics-Comorbidities-Vaccines-Therapeutic-Development-Blood-Type-and-Long-Covid.pdf (Full text PDF file)

Miscellaneous neuromuscular symptoms and signs in long Covid

Abstract:

We have completed the 3rd year of the Covid-19 pandemic. In the early stages of the disease, we were faced with a wide variety of symptoms and signs, including the neuromuscular system, as well as life-threatening cardiopulmonary, neurovascular and immune complications.

In our study, we questioned fatigue, myalgia, arthralgia, dyspnea, headache, dizziness, neck pain, back pain, low back pain, knee-hip-foot joint pain, vascular claudication (lower extremity pain/cramp), neuropathic pain, morning stiffness, joint swelling, pernio, imbalance in walking in patients (N=111; 65 female, 29 male) aged 20-59 years, who applied to our outpatient clinic in the last 1 year and had Covid-19.

The mean time after Covid-19 was 5.8 ±2.1 months. The duration of Covid-19 treatment was a minimum of 5 days and a maximum of 12 days (median=5 days). Weight loss in 14.4% (median=3.5 kg), anorexia 17.1%, myalgia 41.4% (visual analog scale, VAS=5.1±1.9 cm), arthralgia 24.3% (VAS=5.1±2 cm), fatigue 63.1%, joint swelling 1.8%, pernio sign 0.9%, morning stiffness 7.2% (median=15 min, min 5-maximum 60 min), headache 39.6%, neuropathic pain 15.3%, effort dyspnea 38.7%, 30 second chair stand test= 14.9 ±3.6, vascular claudication symptom 11.7%, neck pain 27.0%, low back pain 30.6%, back pain 36%, hip-knee-foot pain 18.0%, gait imbalance 1.8%, dizziness 18.9% were observed. While fatigue (p=0.05), headache (p=0.04), and dyspnea (p=0.021) complaints were higher in males; VAS (arthralgia) was found higher in females (p=0.026).

In the post-Covid-19 period, we see many neuromuscular symptoms and signs, especially fatigue, myalgia, headache and back pain. In addition, lower extremity vascular claudication and neuropathic pain related with chronic pain should not be overlooked in these patients.

Source: Koca TT, Erzurumluoglu O, Kocyigit BF. Miscellaneous neuromuscular symptoms and signs in long Covid. Med Science. 2023;12(1):238-43. https://www.medicinescience.org/article/3381 (Full text)

Sex differences in post-exercise fatigue and function in myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

To assess biobehavioral sex differences in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) utilizing a low burden exercise protocol, 22 females and 15 males with ME/CFS and 14 healthy controls underwent two six-min walk tests.

Fifteen daily assessments were scheduled for fatigue and function ratings and heart monitoring. Six-min walk tests were conducted on days 8 and 9. The ME/CFS group showed high self-report fatigue and impaired physical function, whereas healthy controls did not show fatigue or function abnormalities.

In patients, no significant post-exercise changes were found for heart rate variability (HRV); however, heart rate decreased in ME/CFS males from Day 14 to Day 15 (p = 0.046). Female patients showed increased fatigue (p = 0.006) after the initial walk test, but a downward slope (p = 0.008) in fatigue following the second walk test. Male patients showed a decrease in self-report work limitation in the days after exercise (p = 0.046). The healthy control group evidenced a decrease in HRV after the walk tests from Day 9-14 (p = 0.038).

This pilot study did not confirm hypotheses that females as compared to males would show slower exercise recovery on autonomic or self-report (e.g. fatigue) measures. A more exertion-sensitive test may be required to document prolonged post-exertional abnormalities in ME/CFS.

Trial registration: NCT NCT03331419.

Source: Friedberg F, Adamowicz JL, Bruckenthal P, Milazzo M, Ramjan S, Zhang X, Yang J. Sex differences in post-exercise fatigue and function in myalgic encephalomyelitis/chronic fatigue syndrome. Sci Rep. 2023 Apr 3;13(1):5442. doi: 10.1038/s41598-023-32581-w. PMID: 37012343. https://www.nature.com/articles/s41598-023-32581-w (Full text)

Neurocognitive and psychiatric symptoms following infection with COVID-19: Evidence from laboratory and population studies

Abstract:

Objective: The objective of the current investigation was to examine associations between symptomatic COVID-19 history, neurocognitive function, and psychiatric symptoms using cognitive task performance, functional brain imaging, and a prospective population survey.

Methods: Study 1 was a laboratory study conducted between 3 May 2022 and 16 Nov 2022 involving 120 fully vaccinated community dwelling adults between 18 and 84 years of age (Mage = 31.96 (SD = 20.71), 63.3% female). In this cross-sectional study we examined the association between symptomatic COVID-19 infection history and performance on three computer tasks assessing cognitive function (Flanker interference, delay discounting and simple reaction time) and measured oxygen saturation within the prefrontal cortex using functional near infrared spectroscopy (fNIRS). Study 2 was a 2-wave population survey undertaken between 28 September 2021 and 21 March 2022, examining the prospective relationship between symptomatic COVID-19 and self-reported symptoms of cognitive dysfunction, depressive symptoms, anxiety symptoms, and agitation at 6-month follow up. The sample (N = 2,002, M age = 37.0, SD = 10.4; 60.8% female) was collected using a quota process to ensure equal numbers of vaccinated and unvaccinated individuals. Structural equation modelling with latent variables was performed on the population-level data, evaluating the fit of the proposed mediational model of symptomatic COVID-19 to psychiatric symptoms through cognitive dysfunction.

Results: Findings from Study 1 revealed significant effects of symptomatic COVID-19 history on Flanker interference and delay discounting. Effects on flanker performance were significantly stronger among older adult women (effect: 9.603, SE = 4.452, t = 2.157, p = .033), and were accompanied by task-related changes cerebral oxygenation at the right superior frontal gyrus (F (1, 143.1) = 4.729, p = .031). Additionally, those with a symptomatic COVID-19 infection history showed evidence of amplified delay discounting (coefficient = 0.4554, SE = 0.2208, t = 2.0629, p = .041). In Study 2, baseline symptomatic COVID-19 history was associated with self-reported cognitive dysfunction and a latent variable reflecting psychiatric symptoms of anxiety, depression and agitation at follow-up. Mediational analyses revealed evidence of cognitive mediation of clinically significant psychiatric outcomes: depression (indirect effect = 0.077, SE = 0.026, p = .003) and generalized anxiety (indirect effect = 0.060, SE = 0.021, p = .004).

Conclusions: Converging findings from laboratory and population survey data support the conclusion that symptomatic COVID-19 infection is associated with task-related, functional imaging and self-reported indices of cognitive dysfunction as well as psychiatric symptoms. In some cases, these findings appear to be more amplified among women than men, and among older women than younger.

Source: Hall PA, Ayaz H, Meng G, Hudson A, Sakib MN, Quah ACK, Agar TK, Lee JA, Boudreau C, Fong GT. Neurocognitive and psychiatric symptoms following infection with COVID-19: Evidence from laboratory and population studies. Brain Behav Immun Health. 2023 Mar;28:100595. doi: 10.1016/j.bbih.2023.100595. Epub 2023 Jan 24. PMID: 36713476; PMCID: PMC9870612. https://www.sciencedirect.com/science/article/pii/S2666354623000091?via%3Dihub (Full study)

Racial, ethnic, and sex disparities in the incidence and cognitive symptomology of long COVID-19

Abstract:

Background: The pandemic has highlighted and exacerbated health inequities in both acute coronavirus disease 2019 (COVID-19) and its longer-term sequelae. Given the heterogeneity in definitions of long COVID and the lack of centralized registries of patients with the disease, little is known about the differential prevalence among racial, ethnic, and sex subgroups. This study examines long COVID among Black, White, Asian, and Hispanic Americans and evaluates differences in the associated cognitive symptomology.

Method: Data from four releases of the Census Bureau’s Household Pulse Survey detailing COVID-19 incidence and the duration and type of symptoms among a nationally representative sample of adults from June 1, 2022, through October 17, 2022, were combined. Binary logistic regression assessed the relative likelihood of long COVID among those who had been diagnosed COVID between racial, ethnic, and sex subgroups. Among those reporting long COVID, differences in the prevalence of difficulty understanding and difficulty remembering were assessed. Empirical models accounted for household, regional, vaccination, and insurance differences between respondents. Two-stage selection models were applied to test the robustness of the results.

Results: Among respondents who tested positive for COVID-19, Blacks (OR=1.097, CI=1.034-1.163), females (OR=1.849, CI=1.794-1.907), and Hispanics (OR=1.349, CI=1.286-1.414) were more likely to experience long COVID (symptoms lasting for 3 months or longer) compared to Whites, males, and non-Hispanics respectively. However, those with private health insurance (OR=0.634, CI=0.611-0.658) and who received the COVID vaccine (OR=0.901, CI=0.864-0.94) were less likely to have endured COVID symptoms than their counterparts. Symptoms of long COVID varied significantly between population subgroups. Compared to Whites, Blacks were more likely to have trouble remembering (OR=1.878, CI=1.765-1.808) while Hispanics were more likely to report difficult understanding (OR=1.827, CI=1.413, 2.362). Females, compared to males, were less likely to experience trouble understanding (OR=0.664, CI=0.537, 0.821), but more likely to report trouble remembering (OR=1.34, CI=1.237, 1.451).

Conclusions: Long COVID is more prevalent among Blacks, Hispanics, and females, but each group appears to experience long COVID differently. Therefore, additional research is needed to determine the best method to treat and manage this poorly understood condition.

Source: Jacobs MM, Evans E, Ellis C. Racial, ethnic, and sex disparities in the incidence and cognitive symptomology of long COVID-19. J Natl Med Assoc. 2023 Feb 13:S0027-9684(23)00025-1. doi: 10.1016/j.jnma.2023.01.016. Epub ahead of print. PMID: 36792456; PMCID: PMC9923441. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9923441/ (Full text)