Are Men at Greater Risk From COVID-19?

Check out this answer from Consensus:

The collective evidence indicates that men are at greater risk from COVID-19 compared to women. This increased risk is attributed to a combination of biological, behavioral, and psychosocial factors. Men are more likely to experience severe disease, require intensive care, and have higher mortality rates. Understanding these differences is crucial for developing targeted clinical and public health interventions to mitigate the impact of COVID-19 on men.

The COVID-19 pandemic has prompted extensive research into the factors influencing the severity and outcomes of the disease. One area of focus has been the potential differences in risk between men and women. This synthesis examines whether men are at greater risk from COVID-19 based on data from multiple research studies.

Key Insights

• Higher Risk of Severe Outcomes in Men:
  • Men have a higher risk of severe COVID-19 outcomes, including intensive care unit (ICU) admission and death, compared to women1 2 4 5 7.
  • Men are more likely to require hospitalization and have severe disease progression2 4.
• Biological and Behavioral Factors:
  • Biological factors such as higher expression of ACE-2 receptors, sex-based immunological differences, and potentially lower testosterone levels in men may contribute to worse outcomes8 9 10.
  • Behavioral factors, including higher levels of smoking and drinking among men, and less responsible attitudes towards preventive measures, also play a role8.
• Global and Temporal Trends:
  • The increased risk for men is a global phenomenon observed across different regions and time periods1 4.
  • Temporal trends indicate that while the relative risk for infection and severity has varied, men consistently show higher mortality rates compared to women4.
• Impact of Comorbidities:
  • Even after adjusting for age and comorbidities, men still exhibit a higher risk of severe outcomes and death from COVID-195 6.
• Psychosocial and Health Impacts:
  • COVID-19 has broader health impacts on men, including potential effects on mental health, fertility, and sexual function3 9.

Are men at greater risk from COVID-19?

Jeremy Rossman has answered Likely

An expert from University of Kent in Virology, Infectious diseases

For COVID-19, age and sex appear to be strong predictors of who lives and who dies.

The fatality rate for the disease is estimated to be 0.66%, according to data from China. In other words, 0.66% of people who are formally diagnosed with COVID-19, die. But the rate varies dramatically for different age groups, ranging from 0.0016% for children under ten to 7.8% in people over 79. Similar rates are seen in New York city.

Similar trends are seen with the percentage of COVID-19 patients that need hospitalisation (ranging from 0% in under tens to 18.4% in over 79s). Yet those over 79 do not appear to be more likely to become infected, as they represent just 3.15% of the total confirmed cases.

Recent studies have shown that gender is a risk factor, too. Men are at a greater risk of dying from COVID-19 than women.

Data from China shows that men have 1.65 times the risk of dying from COVID-19 and in New York city, the rate is 1.77 times greater. Yet overall, men and women have roughly similar risks of getting the virus.

A declining immune system?

The ability of the human immune system to fight off pathogens declines over time and is significantly reduced in those over 70. Recent results show that in bad cases of COVID-19, there is a severe deficiency in certain classes of immune cells that fight off infections. These immune cells are known to be less active in the elderly, suggesting that an age-related decline in immune function may put the elderly at risk of more severe COVID-19 disease. Yet many of the most severe cases of COVID-19 are associated with over activation of the immune system.

The immune system is composed of many different parts and so it is possible to have suppression of one component and over-activation of another. But if the age-dependency of COVID-19 disease was specifically due to immune function, we would expect babies to also show severe disease, as their immune systems are still developing. This is what is seen in most seasonal flu epidemics, where those under two and those over 65 are at a greater risk of severe disease.

Changes in ACE2 levels?

In contrast to the flu, the 2003 Sars epidemic showed a fatality rate that increased with age similar to COVID-19 (4.26% for those under 44, rising to 64.2% for those over 74) and a 1.66 times greater fatality rate in men compared with women. The absence of severe infection in babies suggests that the age and gender disparity for COVID-19 may not be due to differences in immune response but rather something specific to the Sars viruses.

Both the 2003 SARS-CoV-1 and the current SARS-CoV-2 viruses bind to and use a protein known as ACE2 to gain entry into cells. ACE2 normally helps to regulate blood pressure and is found on the surface of many different cells, including those that line the lungs. The amount of ACE2 on human cells is higher in men and increases with age.

Certain variants of the ACE2 gene in humans are also associated with different levels of ACE2 expression, and the amount of ACE2 in different populations is somewhat correlated with COVID-19 disease. Also, hypertension (high blood pressure) is known to be a significant age-dependent risk factor for severe COVID-19 disease. Hypertension is typically treated with ACE-inhibitors that have also been shown to increase the amount of ACE2.

However, it appears that COVID-19 infection results in decreased ACE2 levels, which are associated with more severe lung disease. It is not clear what happens when ACE2 levels are high to begin with, such as in older men. Simply increasing ACE2 levels does not appear to cause more severe disease.

In addition, a recent clinical trial showed that ACE-inhibitor use was associated with less severe COVID-19 disease.

ACE2 is just one component of a complex regulatory system and so changes in ACE2 levels and action may have more complicated effects on disease progression than just virus entry into cells. These effects may change as the disease progresses and the immune system is activated.

Exposure to other coronaviruses?

Other related coronaviruses have been found to cause pneumonia in elderly patients and the likelihood of exposure to a virus increases with age. We also know that the human immune system can show some cross-reactivity between different coronaviruses.

Normally, recovery from an infection generates an immune memory that protects a person from being reinfected with the same pathogen. Cross-reactivity occurs when the immune system responds to a new pathogen as if it already had a memory of it. Sometimes this can protect against infection, but sometimes it can make the disease worse.

As severe COVID-19 disease appears to result from an over-activation of the immune system, it is possible that previous exposure to related coronaviruses may create an immune memory that primes the system to overreact to COVID-19. This process could be more prevalent in older people with more past exposure to other coronaviruses.

No data shows this cross-reactivity occurs in COVID-19 disease, but analysis of COVID-19 severe infection rates in areas with previous related coronavirus outbreaks could shed some light on the matter.

A simple explanation?

It is also possible that the reason why more men and elderly people are dying from COVID-19 is more simple. We know that the risk of fatal COVID-19 disease is almost twice as great if the person has underlying health conditions. Most of these health conditions show increasing prevalence with age, such as hypertension, which increases in occurrence from 7.5% in those under 40 to over 63% in those over 60. This increasing rate of predisposing health conditions could directly increase the risk of severe COVID-19 disease.

We don’t know why these health conditions put people at risk of more severe disease. We also are just beginning to understand how COVID-19 causes disease in the first place. By understanding the process of severe COVID-19 disease we will be better placed to both mitigate the risks to specific populations and to develop interventions that block the most severe disease and possibly even prevent fatalities.

I have adapted this answer from my original article in The Conversation

Are men at greater risk from COVID-19?

Philip Goulder has answered Likely

An expert from Oxford University in Immunology, Paediatrics

It is becoming increasingly recognised that there are substantial differences in the immune system between males and females and that these have significant impact on outcome from a wide range of infectious diseases. The immune response throughout life to vaccines and infections is typically more aggressive and more effective in females compared to males.

Several factors contribute to this, but these include the fact that females have two X chromosomes compared to one in males, and a number of critical immune genes are located on the X chromosome. In particular, the protein by which viruses such as coronavirus are sensed is encoded on the X chromosome. As a result, this protein is expressed at twice the dose on many immune cells in females compared to males, and the immune response to coronavirus is therefore amplified in females.

Apart from the immune sex differences that impact on mortality from infections such as coronavirus, there are important behavioural differences between the sexes, for example in smoking, which affect the level of pre-existing disease such as heart disease, chronic lung disease and cancer. These have a huge impact on the outcome from infections such as coronavirus. The sex differential in smoking is especially marked in some countries such as China, where 50% of men smoke compared to 5% in women.