Estradiol and Dihydrotestosterone Levels in COVID-19 Patients

MacArthur, Taleen A.; Goswami, Julie; Ramachandran, Dhanya; Price-Troska, Tammy; Lundell, Kaitlin; Ballinger, Beth A.; Loomis, Erica A.; Heller, Stephanie F.; Stephens, Dan P.; Hurt, Ryan T.; Salonen, Bradley R.; Ganesh, Ravindra; Spears, Grant M.; Bailey, Kent R.; Chaudry, Irshad H.; Park, Myung S.

doi:10.1016/j.mayocp.2022.12.018

Cited by 5 publications

(5 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In our study, we failed to find the predicted attenuation of IL-1β and TNF-α, although IL-6 tended to resolve faster in females. However, our results are consistent with the work of MacArthur et al ( 56 ) who found that the effects of sex hormones on COVID-19 outcomes are not mediated through cytokine changes in patients who are hospitalized.…”

Section: Discussionsupporting

confidence: 93%

“…Sex differences in infectious disease outcomes are not unique to COVID-19 and research generally shows that females have a protective advantage, due in part to relatively higher levels of estrogens than in men ( 54 ). Further evidence for a protective role of estrogens in COVID-19 is found in the higher mortality rates in postmenopausal women and mitigation with estrogen supplementation ( 55 , 56 ). The mechanisms by which estrogens mediate protection against adverse outcomes including cardiac injury have not been established, but several hypotheses have been advanced including a tempered immune response.…”

Section: Discussionmentioning

confidence: 99%

“…As noted above, we see some signs of a stronger cytokine response in the hearts of male ferrets, although these patterns are restricted to a tendency toward a faster resolution in females. Interestingly, while testosterone has been proposed as a risk for adverse COVID-19 outcomes, numerous studies report that low testosterone is associated with a higher risk of infection and more severe illness ( 60 ), but only in males ( 56 ). The impact of low testosterone on cardiac injury in patients with COVID-19 has not been investigated.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Sex differences in the cardiac stress response following SARS-CoV-2 infection of ferrets

Rouhana,

Jacyniak,

Francis

et al. 2023

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection damages the heart, increasing the risk of adverse cardiovascular events. Female sex protects against complications of infection: females are less likely to experience severe illness or death, although their risk for Post-Acute Sequelae of COVID-19 ("Long COVID") is higher than males. Despite an important role for the heart in COVID-19 outcomes, molecular elements in the heart impacted by SARS-CoV-2 are poorly understood. Similarly, the role sex has on the myocardial effects of SARS-CoV-2 infection have not been investigated at a molecular level. We intranasally inoculated female and male ferrets with SARS-CoV-2 and assessed myocardial stress signals, inflammation, and the innate immune response for 14 days. Myocardial phosphorylated GSK3αβ decreased at day 2 post-infection (pi) in male ferrets, while females showed no changes. Myocardial levels of p62/SQSTM1 decreased in male ferrets at days 2, 7, and 14 pi while lower baseline levels in females increased on day 2. Phosphorylated ERK1/2 increased in cardiomyocyte nuclei in females on days 2 and 14 pi whereas male ferrets had no changes. Only hearts from females increased fibrosis on day 14 pi. Immune and inflammation markers increased in hearts, with some sex differences. These results are the first to identify myocardial stress responses following SARS-CoV-2 infection and reveal sex differences that may contribute to differential outcomes. Future research is required to define the pathways involving these stress signals to fully understand the myocardial effects of COVID-19 and identify targets that mitigate cardiac injury following SARS-CoV-2 infection.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Sex differences in the cardiac stress response following SARS-CoV-2 infection of ferrets

Rouhana,

Jacyniak,

Francis

et al. 2023

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…Alterations in the fibrin component of the blood clot and occurrence of fibrinolysis have been shown to impact clot structural mechanics and network properties [16][17][18][19][20]. Furthermore, changes to thrombin generation have been observed following injury in both animal models and trauma patients, leading to additional changes in fibrin structure and resulting clot stability [16,19,21,22]. TIC is known to contribute to mortality and altered clot formation, however the impact of traumatic injury on the coagulation system, TIC factors and clot stability have not yet been completely characterized [9,23].…”

Section: Introductionmentioning

confidence: 99%

Injury Severity is a Key Contributor to Coagulation Dysregulation and Fibrinogen Consumption

Gosselin,

Bargoud,

Sawalkar

et al. 2024

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Traumatic injury is a leading cause of death for those under the age of 45, with 40% occurring due to hemorrhage. Severe tissue injury and hypoperfusion lead to marked changes in coagulation, thereby preventing formation of a stable blood clot and increasing hemorrhage associated mortality. Objectives: We aimed to quantify changes in clot formation and mechanics occurring after traumatic injury and the relationship to coagulation kinetics, and fibrinolysis. Methods: Plasma was isolated from injured patients upon arrival to the emergency department. Coagulation kinetics and mechanics of healthy donors and patient plasma were compared with rheological, turbidimetric and thrombin generation assays. ELISAs were performed to determine tissue plasminogen activator (tPA) and D-dimer concentration, as fibrinolytic markers. Results: Sixty-three patients were included in the study. The median injury severity score (ISS) was 17, median age was 37.5 years old, and mortality rate was 30%. Rheological, turbidimetric and thrombin generation assays indicated that trauma patients on average, and especially deceased patients, exhibited reduced clot stiffness, increased fibrinolysis and reduced thrombin generation compared to healthy donors. Fibrinogen concentration, clot stiffness, D-dimer and tPA all demonstrated significant direct correlation to increasing ISS. Machine learning algorithms identified and highlighted the importance of clinical factors on determining patient outcomes. Conclusions: Viscoelastic and biochemical assays indicate significant contributors and predictors of mortality for improved patient treatment and therapeutic target detection.

show abstract

“…Finally, reduced levels of estradiol and dihydrotestosterone have been found in female and male COVID-19 patients with sex-specific patterns of hypogonadism [ 22 ]. Very low testosterone levels associate with severe forms of COVID-19 in male patients, while in females, both the anti-Müllerian hormone and estradiol showed a negative correlation with severity of infection [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Transcriptional changes in multiple endocrine organs from lethal cases of COVID-19

et al. 2023

View full text Add to dashboard Cite

Altered circulating hormone and metabolite levels have been reported during and post-COVID-19. Yet, studies of gene expression at the tissue level capable of identifying the causes of endocrine dysfunctions are lacking. Transcript levels of endocrine-specific genes were analyzed in five endocrine organs of lethal COVID-19 cases. Overall, 116 autoptic specimens from 77 individuals (50 COVID-19 cases and 27 uninfected controls) were included. Samples were tested for the SARS-CoV-2 genome. The adrenals, pancreas, ovary, thyroid, and white adipose tissue (WAT) were investigated. Transcript levels of 42 endocrine-specific and 3 interferon-stimulated genes (ISGs) were measured and compared between COVID-19 cases (virus-positive and virus-negative in each tissue) and uninfected controls. ISG transcript levels were enhanced in SARS-CoV-2-positive tissues. Endocrine-specific genes (e.g., HSD3B2, INS, IAPP, TSHR, FOXE1, LEP, and CRYGD) were deregulated in COVID-19 cases in an organ-specific manner. Transcription of organ-specific genes was suppressed in virus-positive specimens of the ovary, pancreas, and thyroid but enhanced in the adrenals. In WAT of COVID-19 cases, transcription of ISGs and leptin was enhanced independently of virus detection in tissue. Though vaccination and prior infection have a protective role against acute and long-term effects of COVID-19, clinicians must be aware that endocrine manifestations can derive from virus-induced and/or stress-induced transcriptional changes of individual endocrine genes. Key messages • SARS-CoV-2 can infect adipose tissue, adrenals, ovary, pancreas and thyroid. • Infection of endocrine organs induces interferon response. • Interferon response is observed in adipose tissue independently of virus presence. • Endocrine-specific genes are deregulated in an organ-specific manner in COVID-19. • Transcription of crucial genes such as INS, TSHR and LEP is altered in COVID-19.

show abstract

Estradiol and Dihydrotestosterone Levels in COVID-19 Patients

Cited by 5 publications

References 18 publications

Sex differences in the cardiac stress response following SARS-CoV-2 infection of ferrets

Sex differences in the cardiac stress response following SARS-CoV-2 infection of ferrets

Injury Severity is a Key Contributor to Coagulation Dysregulation and Fibrinogen Consumption

Transcriptional changes in multiple endocrine organs from lethal cases of COVID-19

Contact Info

Product

Resources

About