The current novel coronavirus disease 2019 (COVID-19) pandemic is revealing profound differences between men and women in disease outcomes worldwide. In the United States, there has been inconsistent reporting and analyses of male-female differences in COVID-19 cases, hospitalizations, and deaths. We seek to raise awareness about the male-biased severe outcomes from COVID-19, highlighting the mechanistic differences including in the expression and activity of angiotensin-converting enzyme 2 (ACE2) as well as in antiviral immunity. We also highlight how sex differences in comorbidities, which can be associated with both age and race, impact male-biased outcomes from COVID-19. We are in the midst of a pandemic. Many of us predicted that the next "100 year pandemic" would be caused by an influenza A virus, like the H1N1 virus that caused the 1918 influenza pandemic. Instead, the current pandemic is caused by a novel β-coronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). Currently, there are almost 2 million cases and over 100,000 deaths worldwide from the disease caused by this virus, called the novel coronavirus disease 2019 (COVID-19). Like the 1918 influenza pandemic [1], men are at greater risk of more severe COVID-19 outcomes than women, with both sex (i.e., biological differences) and gender (i.e., sociocultural and behavioral differences) playing fundamental roles. The initial reports from China, followed by data from several countries in Europe, have highlighted that there are roughly similar numbers of confirmed SARS-CoV2 cases between men and women. The severity of COVID-19, as measured by hospitalization, admission to intensive care units, and rates of fatality, however, has consistently been 2-fold greater for men than women [2], with the Global Health 50/50 research initiative providing real-time sex-disaggregated data from most countries worldwide [3]. Unfortunately, despite the United States currently having the most COVID-19 cases in the world, considerably less attention has been paid to sex-disaggregation of data than in Europe and China. We took this opportunity to evaluate the current situation in the US to both determine if similar patterns of male-female differences are observed and to document which states are or

Vaccine-induced immunity declines with age, which may differ between males and females. Using human sera collected before and 21 days after receipt of the monovalent A/Cal/09 H1N1 vaccine, we evaluated cytokine and antibody responses in adult (18–45 years) and aged (65+ years) individuals. After vaccination, adult females developed greater IL-6 and antibody responses than either adult males or aged females, with female antibody responses being positively associated with concentrations of estradiol. To test whether protection against influenza virus challenge was greater in females than males, we primed and boosted adult (8–10 weeks) and aged (68–70 weeks) male and female mice with an inactivated A/Cal/09 H1N1 vaccine or no vaccine and challenged with a drift variant A/Cal/09 virus. As compared with unvaccinated mice, vaccinated adult, but not aged, mice experienced less morbidity and better pulmonary viral clearance following challenge, regardless of sex. Vaccinated adult female mice developed antibody responses that were of greater quantity and quality and more protective than vaccinated adult males. Sex differences in vaccine efficacy diminished with age in mice. To determine the role of sex steroids in vaccine-induced immune responses, adult mice were gonadectomized and hormones (estradiol in females and testosterone in males) were replaced in subsets of animals before vaccination. Vaccine-induced antibody responses were increased in females by estradiol and decreased in males by testosterone. The benefit of elevated estradiol on antibody responses and protection against influenza in females is diminished with age in both mice and humans.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global health problem. Although the respiratory system is the main impaired organ, conjunctivitis is one of its common findings. However, it is not yet understood if SARS-CoV-2 can infect the eye and if the ocular surface can be a potential route of SARS-CoV-2 transmissions. Our review focuses on the viral entry mechanisms to give a better understanding of the interaction between SARS-CoV-2 and the eye. We highlighted findings that give evidence for multiple potential receptors of SARS-CoV-2 on the ocular surface. Additionally, we focused on data concerning the detection of viral RNA and its spike protein in the various ocular tissues from patients. However, the expression level seemed to be relatively low compared to the respiratory tissues as a result of a unique environment surrounding the ocular surface and the innate immune response of SARS-CoV-2. Nevertheless, our review suggests the ocular surface as a potential route for SARS-CoV-2 transmission, and as a result of this study we strongly recommend the protection of the eyes for ophthalmologists and patients at risk.

No abstract