Sex- and gender-related differences linked to SARS-CoV-2 infection among the participants in the web-based EPICOVID19 survey: the hormonal hypothesis

Prinelli, Federica; Trevisan, Caterina; Noale, Marianna; Franchini, Michela; Giacomelli, Andrea; Cori, Liliana; Jesuthasan, Nithiya; Incalzi, Raffaele Antonelli; Maggi, Stefania; Adorni, Fulvio

doi:10.1016/j.maturitas.2021.11.015

Cited by 18 publications

(12 citation statements)

References 34 publications

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“… 26 A web-based COVID-19 survey in Italy that included 6873 participants (mean age, 47.9 ± 14.1 years; 65.8% women) showed that women had lower odds than men of a positive nasopharyngeal swab test (adjusted OR, 0.75; 95% CI, 0.66–0.85) and of having a severe infection (adjusted OR, 0.46; 95% CI, 0.37–0.57). 27 This sex-related discrepancy of disease severity and high mortality in patients with COVID-19 may be due to hormonal differences, socioeconomic factors, genetic susceptibility, sex-related comorbidities, and habits such as smoking and alcohol consumption. 28 , 29 In addition, recent structural and functional analyses of female sex hormones and their relation to SARS-CoV-2 cell entry revealed a putative mechanism whereby female sex hormones may protect against the development of a severe infection in patients with COVID-19.…”

Section: Discussionmentioning

confidence: 99%

Factors associated with failure of high-flow nasal cannula oxygen therapy in patients with severe COVID-19: a retrospective case series

Yin

et al. 2022

J Int Med Res

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Objective To identify factors associated with high-flow nasal cannula (HFNC) therapy failure in patients with severe COVID-19. Methods We retrospectively examined clinical and laboratory data upon admission, treatments, and outcomes of patients with severe COVID-19. Sequential Organ Failure Assessment (SOFA) scores were also calculated. Results Of 54 patients with severe COVID-19, HFNC therapy was successful in 28 (51.9%) and unsuccessful in 26 (48.1%). HFNC therapy failure was more common in patients aged ≥60 years and in men. Compared with patients with successful HFNC therapy, patients with HFNC therapy failure had higher percentages of fatigue, anorexia, and cardiovascular disease; a longer time from symptom onset to diagnosis; higher SOFA scores; a higher body temperature, respiratory rate, and heart rate; more complications, including acute respiratory distress syndrome, septic shock, myocardial damage, and acute kidney injury; a higher C-reactive protein concentration, neutrophil count, and prothrombin time; and a lower arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2). However, male sex, a low PaO2/FiO2, and a high SOFA score were the only independent factors significantly associated with HFNC therapy failure. Conclusions Male sex, a low PaO2/FiO2, and a high SOFA score were independently associated with HFNC therapy failure in patients with severe COVID-19.

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Section: Discussionmentioning

confidence: 99%

Factors associated with failure of high-flow nasal cannula oxygen therapy in patients with severe COVID-19: a retrospective case series

Yin

et al. 2022

J Int Med Res

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“…Interestingly, it has been reported that there are some sex-and gender-related differences linked to SARS-CoV-2 infection (Prinelli et al, 2022). Male patients frequently have severe COVID-19 symptoms such as fever and pneumonia, leading to worse disease progression.…”

Section: Sars-cov-2 and Covid-19mentioning

confidence: 99%

“…Male patients frequently have severe COVID-19 symptoms such as fever and pneumonia, leading to worse disease progression. However, females are more likely to present atypical symptoms characterized by sore throat/rhinorrhea, gastrointestinal disturbances, headache, conjunctivitis, and palpitations that are associated with less severe outcomes (Prinelli et al, 2022). These sex differences rely on the disparities in immune responses throughout life, which are influenced by age and reproductive status.…”

Section: Sars-cov-2 and Covid-19mentioning

confidence: 99%

“…Furthermore, high estrogen concentrations in premenopausal women might lead to an overexpression of ACE2 in females, protecting them by inducing antiinflammatory responses. On the contrary, low estrogen levels in males may contribute to higher disease susceptibility and death rates (Prinelli et al, 2022). "Androgens could also promote the transcription of the TMPRSS2 gene facilitating viral entry into the cells and decreasing the antibody response to viral infections" (Prinelli et al, 2022).…”

Section: Sars-cov-2 and Covid-19mentioning

confidence: 99%

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Role of the renin-angiotensin system in the development of COVID-19-associated neurological manifestations

Méndez-García

Escobedo

Minguer-Uribe

et al. 2022

Front. Cell. Neurosci.

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SARS-CoV-2 causes COVID-19, which has claimed millions of lives. This virus can infect various cells and tissues, including the brain, for which numerous neurological symptoms have been reported, ranging from mild and nonlife-threatening (e.g., headaches, anosmia, dysgeusia, and disorientation) to severe and life-threatening symptoms (e.g., meningitis, ischemic stroke, and cerebral thrombosis). The cellular receptor for SARS-CoV-2 is angiotensinconverting enzyme 2 (ACE2), an enzyme that belongs to the renin-angiotensin system (RAS). RAS is an endocrine system that has been classically associated with regulating blood pressure and fluid and electrolyte balance; however, it is also involved in promoting inflammation, proliferation, fibrogenesis, and lipogenesis. Two pathways constitute the RAS with counter-balancing effects, which is the key to its regulation. The first axis (classical) is composed of angiotensin-converting enzyme (ACE), angiotensin (Ang) II, and angiotensin type 1 receptor (AT1R) as the main effector, which -when activated-increases the production of aldosterone and antidiuretic hormone, sympathetic nervous system tone, blood pressure, vasoconstriction, fibrosis, inflammation, and reactive oxygen species (ROS) production. Both systemic and local classical RAS' within the brain are associated with cognitive impairment, cell death, and inflammation. The second axis (non-classical or alternative) includes ACE2, which converts Ang II to Ang-(1-7), a peptide molecule that activates Mas receptor (MasR) in charge of opposing Ang II/AT1R actions. Thus, the alternative RAS axis enhances cognition, synaptic remodeling, cell survival, cell signal transmission, and antioxidant/anti-inflammatory mechanisms in the brain. In a physiological state, both RAS axes remain balanced. However, some Frontiers in Cellular Neuroscience 01 frontiersin.org Méndez-García et al. 10.3389/fncel.2022.977039factors can dysregulate systemic and local RAS arms. The binding of SARS-CoV-2 to ACE2 causes the internalization and degradation of this enzyme, reducing its activity, and disrupting the balance of systemic and local RAS, which partially explain the appearance of some of the neurological symptoms associated with COVID-19. Therefore, this review aims to analyze the role of RAS in the development of the neurological effects due to SARS-CoV-2 infection. Moreover, we will discuss the RAS-molecular targets that could be used for therapeutic purposes to treat the short and long-term neurological COVID-19-related sequelae.

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“…Epidemiological data have consistently shown since the beginning of the pandemic that both the severity and the mortality of coronavirus disease (COVID-19) are higher in men than in women [1] , [2] . The Global Health 50/50 research initiative confirmed a greater mortality in men despite similar numbers of COVID-19 cases in both genders worldwide [3] .…”

mentioning

confidence: 99%

Gender differences in COVID-19

et al. 2022

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Sex- and gender-related differences linked to SARS-CoV-2 infection among the participants in the web-based EPICOVID19 survey: the hormonal hypothesis

Cited by 18 publications

References 34 publications

Factors associated with failure of high-flow nasal cannula oxygen therapy in patients with severe COVID-19: a retrospective case series

Factors associated with failure of high-flow nasal cannula oxygen therapy in patients with severe COVID-19: a retrospective case series

Role of the renin-angiotensin system in the development of COVID-19-associated neurological manifestations

Gender differences in COVID-19

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