Pub Date : 2023-01-01DOI: 10.1016/B978-0-323-88534-8.00056-0
F. Fang, A. Casadevall
{"title":"Chapter 42 Sex differences in COVID-19 susceptibility – Reductionistic and holistic perspectives","authors":"F. Fang, A. Casadevall","doi":"10.1016/B978-0-323-88534-8.00056-0","DOIUrl":"https://doi.org/10.1016/B978-0-323-88534-8.00056-0","url":null,"abstract":"","PeriodicalId":36473,"journal":{"name":"Italian Journal of Gender-Specific Medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90203031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Brizuela, J. Lenzi, R. Ulloa-Gutiérrez, O. Antúnez-Montes, J. Aida, O. del Águila, E. Arteaga-Menchaca, F. Campos, F. Uribe, A. P. Buitrago, L. M. B. Londoño, J. Gómez-Vargas, A. Yock-Corrales, D. Buonsenso
from IGM webinar May 6, 2021 During the pandemic, several clinical trials for the treatment or prevention of COVID-19 have been conducted with new or repurposed therapeutics and with investigational vaccines. Some of these studies were large randomized controlled trials that led to the approval of new vaccines or to recommending the use of therapeutics for COVID-19. In the context of such studies, women were generally included in a satisfactory proportion versus men. In the trials of therapeutics such as the studies conducted with remdesivir, baracitinib and dexamethasone, at least one third of the patients enrolled were women, reflecting the current proportion of COVID-19 female cases requiring hospitalization and oxygen supplementation. Interestingly, studies with immunomodulators showed some trends towards a reduced effect of the treatment in female patients compared with males, who suffer from a worse prognosis. However, other co-variates may have played a major role in explaining such difference, and more data need therefore to be collected. With respect to vaccines, it is well known that sex is a predictor of susceptibility to specific infections and autoimmune diseases, but it can also influence the response to immunization, which is why it is appropriate to have an adequate representation of females in the clinical trials with vaccines. Pivotal clinical trials conducted to support the approval of COVID-19 vaccines resulted in an equal enrollment across gender. The overall safety and efficacy profile did not differ between males and females for all the vaccines approved. From a safety perspective, the emergent cases of thrombosis with thrombocytopenia with the two approved viral vectored vaccines were reportedly more prevalent in females than males. More data are needed to further characterize the incidence of this risk by age and gender. Overall, during the pandemic large clinical trials to support the approval of vaccines and therapeutics included women to an adequate extent. Such effort allowed for the regulatory assessment of the safety and efficacy of vaccines and therapeutics also in females, thus further supporting their approval.
{"title":"Considerations on the study of drugs and vaccines in women during the covid-19 pandemic. The ema perspective","authors":"M. Cavaleri","doi":"10.1723/3673.36601","DOIUrl":"https://doi.org/10.1723/3673.36601","url":null,"abstract":"from IGM webinar May 6, 2021 During the pandemic, several clinical trials for the treatment or prevention of COVID-19 have been conducted with new or repurposed therapeutics and with investigational vaccines. Some of these studies were large randomized controlled trials that led to the approval of new vaccines or to recommending the use of therapeutics for COVID-19. In the context of such studies, women were generally included in a satisfactory proportion versus men. In the trials of therapeutics such as the studies conducted with remdesivir, baracitinib and dexamethasone, at least one third of the patients enrolled were women, reflecting the current proportion of COVID-19 female cases requiring hospitalization and oxygen supplementation. Interestingly, studies with immunomodulators showed some trends towards a reduced effect of the treatment in female patients compared with males, who suffer from a worse prognosis. However, other co-variates may have played a major role in explaining such difference, and more data need therefore to be collected. With respect to vaccines, it is well known that sex is a predictor of susceptibility to specific infections and autoimmune diseases, but it can also influence the response to immunization, which is why it is appropriate to have an adequate representation of females in the clinical trials with vaccines. Pivotal clinical trials conducted to support the approval of COVID-19 vaccines resulted in an equal enrollment across gender. The overall safety and efficacy profile did not differ between males and females for all the vaccines approved. From a safety perspective, the emergent cases of thrombosis with thrombocytopenia with the two approved viral vectored vaccines were reportedly more prevalent in females than males. More data are needed to further characterize the incidence of this risk by age and gender. Overall, during the pandemic large clinical trials to support the approval of vaccines and therapeutics included women to an adequate extent. Such effort allowed for the regulatory assessment of the safety and efficacy of vaccines and therapeutics also in females, thus further supporting their approval.","PeriodicalId":36473,"journal":{"name":"Italian Journal of Gender-Specific Medicine","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85609920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P. Falcetta, M. Mantuano, R. Giannarelli, A. Coppelli, S. Del Prato
The coronavirus disease 2019 (COVID-19) has rapidly spread all over the world, causing a great number of casualties. From the very beginning of the pandemic, it has become apparent that there are multiple risk factors associated with an increased risk of disease severity and death. These include older age, smoking and several underlying comorbidities, as well as gender.1 Susceptibility for SARS-CoV-2 infection appears to be similar in men and women, and yet most of the clinical and epidemiological data has shown that almost twice as many men with COVID-19 suffer severe symptoms or death as women.2 Despite a similar incidence between the two genders, men consistently show a more severe phenotype and an increased mortality rate (62.4%) across age groups at global level.3 A large population-based study performed in England, which included over 17 million adults and 10,926 COVID-19-related deaths, found that males had a significantly higher risk of death (HR 1.59; 95% CI, 1.53-1.65) than females.4 A recently published review reported that, overall, males account for 59-75% of all COVID-19 deaths.5 Sexual dimorphism in COVID-19 should not come as a surprise, because it is well known that men and women respond to viral infections differently, as already reported during other flu outbreaks.6 Many of the genes playing a key role in the immune response are located on the X chromosome, including those involved in determining the innate and adaptive immune responses to viral infections.7 Interestingly, gene encoding for the ACE2 receptor – through which SARS-CoV-2 binds to the cell membrane and enters the host cell – is also located on the X chromosome, so that a higher degree of protein expression could be expected in the female gender, which may increase the risk of viral infection.8 However, a higher ACE2 activity – particularly in the lungs and in the cardiovascular system – has been claimed to confer some protection, which may account for the less severe form of COVID-19 in women.9 Consistent with this hypothesis is the finding that the male heart has less ACE2-expressing cells than the female one,10 which provides support to a sex-specific regulation of ACE2. Nevertheless, such sex-dependent ACE2 expression has not yet been validated in humans, and no relevant influence of medications such as ACE-inhibitors has been documented. Sex differences in the manifestation of infectious diseases have long been attributed also to the influence of sex hormones. Experimental work performed in a murine model of SARS-CoV-2 infection has shown that male animals were more susceptible to infection and had higher mortality than females. Interestingly, the estrogen deprivation obtained by ovariectomy nullified this protection, causing an increase in mortality.11 These results indicate how the balance between androgens and estrogens is likely to play an important role in modulating immune responses in coronavirus infections. Conversely, men receiving androgen deprivation
{"title":"Metabolic issues during the covid-19 pandemic: Gender difference","authors":"P. Falcetta, M. Mantuano, R. Giannarelli, A. Coppelli, S. Del Prato","doi":"10.1723/3673.36600","DOIUrl":"https://doi.org/10.1723/3673.36600","url":null,"abstract":"The coronavirus disease 2019 (COVID-19) has rapidly spread all over the world, causing a great number of casualties. From the very beginning of the pandemic, it has become apparent that there are multiple risk factors associated with an increased risk of disease severity and death. These include older age, smoking and several underlying comorbidities, as well as gender.1 Susceptibility for SARS-CoV-2 infection appears to be similar in men and women, and yet most of the clinical and epidemiological data has shown that almost twice as many men with COVID-19 suffer severe symptoms or death as women.2 Despite a similar incidence between the two genders, men consistently show a more severe phenotype and an increased mortality rate (62.4%) across age groups at global level.3 A large population-based study performed in England, which included over 17 million adults and 10,926 COVID-19-related deaths, found that males had a significantly higher risk of death (HR 1.59; 95% CI, 1.53-1.65) than females.4 A recently published review reported that, overall, males account for 59-75% of all COVID-19 deaths.5 Sexual dimorphism in COVID-19 should not come as a surprise, because it is well known that men and women respond to viral infections differently, as already reported during other flu outbreaks.6 Many of the genes playing a key role in the immune response are located on the X chromosome, including those involved in determining the innate and adaptive immune responses to viral infections.7 Interestingly, gene encoding for the ACE2 receptor – through which SARS-CoV-2 binds to the cell membrane and enters the host cell – is also located on the X chromosome, so that a higher degree of protein expression could be expected in the female gender, which may increase the risk of viral infection.8 However, a higher ACE2 activity – particularly in the lungs and in the cardiovascular system – has been claimed to confer some protection, which may account for the less severe form of COVID-19 in women.9 Consistent with this hypothesis is the finding that the male heart has less ACE2-expressing cells than the female one,10 which provides support to a sex-specific regulation of ACE2. Nevertheless, such sex-dependent ACE2 expression has not yet been validated in humans, and no relevant influence of medications such as ACE-inhibitors has been documented. Sex differences in the manifestation of infectious diseases have long been attributed also to the influence of sex hormones. Experimental work performed in a murine model of SARS-CoV-2 infection has shown that male animals were more susceptible to infection and had higher mortality than females. Interestingly, the estrogen deprivation obtained by ovariectomy nullified this protection, causing an increase in mortality.11 These results indicate how the balance between androgens and estrogens is likely to play an important role in modulating immune responses in coronavirus infections. Conversely, men receiving androgen deprivation","PeriodicalId":36473,"journal":{"name":"Italian Journal of Gender-Specific Medicine","volume":"57 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79418142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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