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Sex-related susceptibility in coronavirus disease 2019 (COVID-19): Proposed mechanisms.

ABSTRACT: The importance of sex differences is increasingly acknowledged in the incidence and treatment of disease. Accumulating clinical evidence demonstrates that sex differences are noticeable in COVID-19, and the prevalence, severity, and mortality rate of COVID-19 are higher among males than females. Sex-related genetic and hormonal factors and immunological responses may underlie the sex bias in COVID-19 patients. Angiotensin-converting enzyme 2 (ACE2) and transmembrane protease/serine subfamily member 2 (TMPRSS2) are essential proteins involved in the cell entry of SARS-CoV-2. Since ACE2 is encoded on the X-chromosome, a double copy of ACE2 in females may compensate for virus-mediated downregulation of ACE2, and thus ACE2-mediated cellular protection is greater in females. The X chromosome also contains the largest immune-related genes leading females to develop more robust immune responses than males. Toll-like receptor-7 (TLR-7), one of the key players in innate immunity, is linked to sex differences in autoimmunity and vaccine efficacy, and its expression is greater in females. Sex steroids also affect immune cell function. Estrogen contributes to higher CD4⁺ and CD8⁺ T cell activation levels, and females have more B cells than males. Sex differences not only affect the severity and progression of the disease, but also alter the efficacy of pharmacological treatment and adverse events related to the drugs/vaccines used against COVID-19. Administration of different drugs/vaccines in different doses or intervals may be useful to eliminate sex differences in efficacy and side/adverse effects. It should be noted that studies should include sex-specific analyses to develop further sex-specific treatments for COVID-19.

SUBMITTER: Aksoyalp ZS

PROVIDER: S-EPMC8486578 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe use of sex to cope with negative affective states during the coronavirus disease 2019 (COVID-19) pandemic may be influenced by various sociodemographic and psychological characteristics.AimWe aimed to examine the effects of social distancing, loneliness, difficulties in emotion regulation, and self-regulation on participants self-reported coping using sex during lockdown in the United Kingdom.MethodsParticipants had to be residents of the United Kingdom, aged between 18-60 years, fluent in English, and had to have an Internet connection. They were instructed not to participate if they had consumed alcohol in the previous 24 hours. A total of 789 participants aged 18-59 years completed an online survey. Participants provided self-report measures of social distancing, loneliness, and difficulties in emotion regulation. A Go/No-Go task was used to assess self-regulation.OutcomesParticipants self-reported their use of sex to cope over a 14-day period during lockdown, as well as retrospectively for a 14-day period immediately preceding lockdown. Coping using sex items included consensual and non-consensual themes.ResultsOverall, there was no increase in coping using sex during lockdown compared with before lockdown. Findings showed that 30% of participants reported increased coping using sex during lockdown compared with before, 29% reported decreased coping using sex, and 41% reported no change. All regression models included age, gender, ethnicity, diagnosis of psychiatric condition, level of education, being at high-risk for difficulties relating to COVID-19, living alone, and diagnosed or suspected COVID-19 as covariates. Being younger, being male, and greater emotion dysregulation were associated with higher coping using sex total and consent subscale scores during lockdown. Being younger, being male, not living alone, and less adherence to social distancing advice were associated with coping using sex with a theme of rape/violence during lockdown.Clinical translationA proportion of participants used sex to cope more often during lockdown compared with before. Less adherence to social distancing advice and emotion dysregulation were associated with using sex to cope during lockdown.Strengths & limitationsStrengths of this study were the large sample size and inclusion of key sociodemographic characteristics as covariates. The main limitations were the cross-sectional design and a sample that was mostly white, educated, and female.ConclusionParticipants who had difficulty regulating emotions were more likely to use sex to cope. It is important that support is available for people who have problems regulating their emotions during the pandemic and that they have access to appropriate help and advice. Gillespie SM, Jones A, Uzieblo K, et al. Coping Using Sex During the Coronavirus Disease 2019 (COVID-19) Outbreak in the United Kingdom. J Sex Med 2020;XX:XXX-XXX.

Project description:The current coronavirus disease 2019 (COVID-19) pneumonia pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading globally at an accelerated rate, with a basic reproduction number (R0) of 2-2.5, indicating that 2-3 persons will be infected from an index patient. A serious public health emergency, it is particularly deadly in vulnerable populations and communities in which healthcare providers are insufficiently prepared to manage the infection. As of March 16, 2020, there are more than 180,000 confirmed cases of COVID-19 worldwide, with more than 7000 related deaths. The SARS-CoV-2 virus has been isolated from asymptomatic individuals, and affected patients continue to be infectious 2 weeks after cessation of symptoms. The substantial morbidity and socioeconomic impact have necessitated drastic measures across all continents, including nationwide lockdowns and border closures. Pregnant women and their fetuses represent a high-risk population during infectious disease outbreaks. To date, the outcomes of 55 pregnant women infected with COVID-19 and 46 neonates have been reported in the literature, with no definite evidence of vertical transmission. Physiological and mechanical changes in pregnancy increase susceptibility to infections in general, particularly when the cardiorespiratory system is affected, and encourage rapid progression to respiratory failure in the gravida. Furthermore, the pregnancy bias toward T-helper 2 (Th2) system dominance, which protects the fetus, leaves the mother vulnerable to viral infections, which are more effectively contained by the Th1 system. These unique challenges mandate an integrated approach to pregnancies affected by SARS-CoV-2. Here we present a review of COVID-19 in pregnancy, bringing together the various factors integral to the understanding of pathophysiology and susceptibility, diagnostic challenges with real-time reverse transcription polymerase chain reaction (RT-PCR) assays, therapeutic controversies, intrauterine transmission, and maternal-fetal complications. We discuss the latest options in antiviral therapy and vaccine development, including the novel use of chloroquine in the management of COVID-19. Fetal surveillance, in view of the predisposition to growth restriction and special considerations during labor and delivery, is addressed. In addition, we focus on keeping frontline obstetric care providers safe while continuing to provide essential services. Our clinical service model is built around the principles of workplace segregation, responsible social distancing, containment of cross-infection to healthcare providers, judicious use of personal protective equipment, and telemedicine. Our aim is to share a framework that can be adopted by tertiary maternity units managing pregnant women in the flux of a pandemic while maintaining the safety of the patient and healthcare provider at its core.

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Sex-related susceptibility in coronavirus disease 2019 (COVID-19): Proposed mechanisms.

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