Men have almost three times the odds of needing admission to intensive care and 40% higher odds of dying from COVID-19 than women, according to a new study led by researchers at UCL, Great Ormond Street Hospital (GOSH) and the University of Cape Town.
The study, published and the largest review of its kind, looked at publicly available data from 92 reports across 47 countries to investigate why COVID-19 may affect genders differently.
Researchers found that in more than three million cases of COVID-19 there were equal proportions of men and women infected. However, of those infected, the odds (likelihood) of adult males needing admission to intensive care were 2.84 times higher and 1.39 times higher of dying from COVID-19 than adult females.
The research team, led by the Centre for Adolescent Rheumatology Versus Arthritis at UCL, UCLH and GOSH (hereafter called the Adolescent Centre), usually focuses on understanding why young female children and adolescents are more like to develop diseases like juvenile idiopathic arthritis and lupus, than boys and young men. They used this knowledge to shed light on the susceptibility of adult males to severe COVID-19.
Co-senior author Dr Claire Deakin (UCL Great Ormond Street Institute of Child Health and the Adolescent Centre) said: "We know from previous work that women generally have a stronger immune response to pathogens that invade the body, like viruses.
"This better initial response could help them to clear the infection more quickly and may explain why men have a higher risk of severe infection with viruses like SARS-CoV-2. Women also have a more robust longer-term protection against pathogens.
"However this stronger immune response in females means that they are more likely to develop diseases where their immune system attack parts of the body - known as autoimmune diseases. Diseases like juvenile idiopathic arthritis are therefore more likely to develop in females."
The authors note that one limitation of the study was that the data did not account for age and individual comorbidities, or ethnicity, which could limit the ability to the predict the role of sex in disease severity.
However, despite these limitations, the data highlight an important trend in the epidemiology of COVID-19, with male sex acting as a risk factor for severe disease.
Co-senior author, Dr Kate Webb (Paediatric Rheumatologist at University of Cape Town), said: "While the disparity between sexes is clear, the underlying explanation is more complex. The reality is that many different risk factors are interacting with each other, but our research strongly suggests that innate differences in the immune systems of males and females play a key role. We hope our research will lead the way for future studies to shed more light and help clinicians protect those who are most vulnerable."
The authors note that previous studies have shown that gender differences in hygiene behaviour could lead to differences in the exposure to infection. For example, men are less likely to wash their hands with soap after entering a restroom and in many cultures men may be more likely to leave the house and enter crowded areas.
Co-senior author and Medical Research Foundation Fellow, Dr Lizzy Rosser (UCL Division of Medicine and the Adolescent Centre) added: "Our data however shows no difference in the numbers of infected cases between the sexes, so sex differences in hygiene behaviour are unlikely to explain the sex difference in disease severity."
The authors note that sex differences in other aspects of physiology further to the immune system could also play a part in the sex bias described in this study. There was preliminary evidence that ACE2, the receptor that this coronavirus binds to enter cells in the lungs could be differently expressed in male and females. However, there are now conflicting reports suggesting this may not be true, further highlighting the importance of differences in the immune system in driving the response reported in this study.
Dr Stephen Simpson, Director of Research at Versus Arthritis, added: "Understanding the role sex plays in our immune systems is an intensive area of research and includes important questions about how sex affects autoimmune conditions like lupus and inflammatory arthritis, as well as viral infections. Versus Arthritis researchers at our Centre for Adolescent Rheumatology bring extensive knowledge and experience of this area so were able to adapt quickly and collaborate with their viral expert peers to improve collective understanding of COVID-19, which could help in developing new treatments and effective vaccines."
The authors hope the study’s findings are important for understanding the relative risk in men and women and the possibility that differences in immune systems between men and women might need to be taken into account for vaccination strategies.