[EXPERT REACTION] COVID-19 Infection Risk: Male vs Female

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There are research suggesting male are more susceptible than females to contract COVID-19. The coronavirus mortality rate also recorded a higher toll on male. In China, the death rate for men was 2.8 percent, compared to 1.7 percent for women, according to the largest analysis of cases by the Chinese Center for Disease Control and Prevention. We asked experts to comment on the risks of COVID-19 infection and mortality rate based on sex.


Associate Prof. Dr Chan Yoke Fun, Virologist & Senior Lecturer at the Department of Medical Microbiology, Faculty of Medicine, University of Malaya, said:

“There are equal numbers of cases between men and women so far, but there seem to be sex differences in mortality. In Malaysia, about 25% (23/100) deaths cases were female. In the U.S., twice as many men have been dying from the virus as women. Similarly, 69% of all coronavirus deaths across Western Europe have been male. Similar patterns have been seen in China and elsewhere. Emerging evidence (nothing solid at the moment) suggests that more men than women are dying, potentially due to chronic diseases are more common in men, ACE2 (receptor for SARS-CoV2) expression more in men than women, smoking as a predisposing factor which is more common in men than women and sex-based immunological differences.” 

Dr Tommy Tong, Immunologist and Senior Lecturer at the Department of Biological Science, Sunway University, said:

“Data from China and other affected nations recorded more male deaths from COVID-19 infection compared to female. However, this does not mean that females are at lesser risk of being infected compared to males. It is still too early to determine why the gender gap is emerging. Lifestyle choice and behaviour may play a role, with men less likely to seek medical help at the first signs of disease or to follow public health advice. In addition, we need to look carefully at the lifestyle of infected individuals. Lifestyle such as drinking, and smoking may have higher incidence of pulmonary and cardiovascular disease, which are the main reasons for COVID-19 deaths.” 

Dr Vinod RMT Balasubramaniam, Virologist & Senior Lecturer at Jeffrey Cheah School of Medicine & Health Sciences, Monash University Malaysia, said:

“The bias in COVID-19 deaths appeared in the first reports out of China and has also been revealed in countries that break down their mortality data by sex. The trend was first seen in China, where one analysis found a fatality rate of 2.8% in men compared with 1.7% in women. Since then, the pattern has been mirrored in France, Germany, Iran, Italy, South Korea, and now in the UK. In Italy, men have accounted for 71% of deaths. In Spain, data released on Thursday suggests twice as many men as women have died. Why are men more vulnerable? Scientists are still finding the reasons for this. Some of the hypothesis includes:

  1. Smoking was suggested as a likely explanation. In China, nearly 50% of men but only about 2% of women smoke, and so underlying differences in lung health were assumed to contribute to men suffering worse symptoms and outcomes. The smoking hypothesis was backed by a paper, published in New England Journal of Medicine, that found smokers made up about 12% of those with less severe symptoms, but 26% of those who ended up in intensive care or died. Smoking might also act as an avenue for getting infected in the first place: smokers touch their lips more and may share contaminated cigarettes.
  2. Some of that discrepancy could be because men are more likely than women to have other health problems, such as hypertension and diabetes. These are among the underlying conditions that raise the risk for severe COVID-19 disease
  3. The differences in the immune system between gender:
    • The many proteins that work together to defend the body against viruses do not operate exactly the same way in males and females. Those biological differences, driven by sex hormones and genes, maybe guarding some women from the deadliest complications of COVID-19. In general, females mount a stronger immune response than males, studies have found. This makes women overall less susceptible to viral infections than men, although how each individual fares is another matter. A stronger immune response also means females are more likely to develop autoimmune diseases, when the immune system attacks one’s own tissue; conversely, a toned-down immune response makes males more prone to having a host of malignant cancers.
    • The sources of the stronger female immune response can be found in both the innate and adaptive immune systems. The innate system provides the first response against a virus, while the adaptive system’s contribution is slightly delayed by the time needed to ramp up antibody production against a new intruder. One component of the innate immune system is called toll-like receptor 7. This protein can recognize molecules found on viruses, thereby outing the pathogens as foreign. The gene for toll-like receptor 7 resides on the X chromosome. Because females have two copies of the X, the body silences one allowing for the right “dose” of X chromosome genes. But some genes escape the shutdown, and there is evidence that this is true for the gene for toll-like receptor 7, researchers reported in Science Immunology in 2018. That can lead to more of the protein being made, giving females more guards looking out for intruders.
    • In a separate study published in the Journal of Immunology in 2017, a comparison of how male and female mice did when infected with a mouse-adapted version of SARS-CoV, the virus that causes SARS was done. Among middle-aged mice, those 8 to 9 months old, all of the males died within eight days of being infected, but only 10 percent of the females did by day 12. Males had higher amounts of the virus in their lungs than females did, suggesting the males weren’t clearing the virus effectively. The males also had a prolonged, unhelpful inflammatory response. When the research team removed the ovaries from 12 female mice to prevent estrogen from being made, about 85 percent of the mice died after infection, compared with close to 20 percent of 12 females with their ovaries. Without estrogen, the female mice were now as sensitive to the infection as male mice. This may provide clues on why male are more susceptible to the severity of infection when compared to females.”
Disclaimer: These comments were complied to provide journalists with a range of expert perspectives on the subject. The views expressed here are the personal opinions of the experts. They do not necessarily reflect the views of the Science Media Centre or any other organisation unless specifically stated. 
Bionotes of experts

Associate Professor Dr Chan Yoke Fun is a virologist focused on the epidemiology and pathogenesis of enterovirus A71, an emerging virus that causes severe neurological disease. She leads a laboratory with research interests in epidemiology and pathogenesis of emerging viruses such as enterovirus A71, chikungunya, and respiratory viruses. With more than 20 years of research experience, she has over 80 publications, and has been involved in many research programs and grants at both national and international levels. Dr. Chan also served as an Associate Editor of BMC Infectious Diseases and guest editor in PLOS Neglected Tropical Diseases. She has multiple joint publications with collaborators from Asia, Europe, and the USA. Her studies have led to a better understanding of how viruses spread and infect humans. 

Dr Tommy Tong graduated from Monash University, Australia with PhD in Immunology. He was working on vaccine development against human immunodeficiency virus (HIV) for his PhD dissertation, before joining Professor James Binley at San Diego for Biomedical Research (SDBRI) in USA to continue his passion in HIV research for 4 years. He is now a lecturer at the Department of Biological Science, Sunway University, and has started his own laboratory to work on HIV vaccine for Malaysians. 

Dr Vinod RMT Balasubramaniam graduated from Asian Institute of Medicine, Science and Technology (AIMST) majoring in Biotechnology in 2007. During this period, he managed to publish several papers on plant genetic engineering, especially on genetically engineered orchids which have resistance towards fungus. In 2008, he worked as a research assistant with Associate Professor Sharifah Syed Hassan in her newly formed infectious disease laboratory in Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia. He embarked on his PhD course working on the various host cellular genes infected with Avian Influenza Virus H5N1 and their protein-protein interactions with viral genes. Graduated with merit in 2014, he continued to work as a post-doctoral fellow before joining Professor Adolfo Garcia-Sastre’s laboratory in Mount Sinai hospital New York, which is one of the leading Influenza research laboratory in the world. He has co-authored various publications (Cell Host Microbe, Nature Microbiology, Plos Pathogens) on various aspects of host response towards different types of viruses.

**All previous posts about COVID-19 here: https://sciencemediacentremalaysia.com/tag/covid-19/

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