With the growing amount of coronavirus research accomplished by researchers globally, the value of the novel coronavirus (SARS-CoV-2) across many relevant research fields has been confirmed. According to big data analytics, the degree of coronavirus infection varies among different genders and different age groups. This review focusing on the analysis of the reasons behind the age preference and gender differences in patients with COVID-19 worldwide.

 

1. Analysis of Age Preference of the SARS-CoV-2

According to current studies, majority of the COVID-19 patients were between ages 36 and 65 years old, confirming to be the group with the highest susceptibility towards SARS-CoV-2 worldwide. In addition, Chinese Center for Disease Control and Prevention (aka China CDC) published a data report in JAMA on April 7th, which summarized the epidemiological characteristics of the COVID-19 outbreak in China. Of the 72,314 cases investigated, 44,672 are diagnosed, and the distribution characteristics of the confirmed COVID-19 cases were as follows: 87% patients are between 30-79 years old, 1% patients are less than 9 years old, just as children at 10-19 years old (1%), and 80 years old or above (3%). In addition, the overall fatality rate is 2.3% - calculated from 44,672 cases with 1,023 deaths, while in severe cases the percentage reaches up to 49%. The fatality rates varied for patients with underlying diseases - cardiovascular disease (10.5%), diabetes (5.6%), chronic respiratory diseases (6.3%), hypertension (6.0%), and cancer (5.6%).

 

Figure 1- Distribution of Age and Infection Characteristics

    (Wu Z and McGoogan JM, 2020)

 

The highest SARS-CoV-2 susceptibility falls into the middle-aged and elderly groups - there are many reasons. On the one hand, middle-to-old aged group is the main area of population distribution from the census statistics, thereby with the largest number of people from this group get infected by SARS-CoV-2. On the other hand, underlying diseases account for a large part for the number of middle-aged and elderly people suffering from underlying diseases is much higher than others.

 

So will children be completely safe during the outbreak of COVID-19? - it's not true. Although the probability of children being infected by SARS-CoV-2 is proved to be very low by the very early data since the outbreak, which results in the mis-judgement of susceptibility of this group towards COVID-19 at the very beginning, however, this still needs further confirmation. On March 15th, Liu Wenjun - a pediatric medical researcher at Southwestern Medical University, published a literature investigation entitled “COVID-19 epidemic: Disease Characteristics in Children” in the Journal of Medical Virology, which describes the epidemiological characteristics of children with the novel coronavirus. According to Liu, children can get infected and be an important participate in family cluster infections. According to the investigation report published by the COVID-19 Response Team of the US Center for Diseases Control and Prevention (CDC) in Morbidity and Mortality Weekly Report (MMWR), “Coronavirus disease 2019 in children- United States, February 12-April 2, 2020,” a total of 149,082 cases with known age is reported from 50 states in the country. Among these cases, 2,572 are children younger than 18 years old, with underlying disease (13%) and hospitalization status (33%). Although most cases of children with COVID-19 are not severe, the symptoms of infants under 1 year old seem to be more serious, which might suggests that children are also important targets for the prevention and control of COVID-19, especially pediatric patients with underlying diseases.

 

Figure 2- Age Characteristics of COVID-19 Infection in Children - in the US (Feb-Apr)

（CDC COVID-19 Response Team，2020）

 

2. Analysis of Gender Difference of the SARS-CoV-2

There is an statement that once appeared after the COVID-19 pandemic - infection rate of male is higher than that of female. This statement is not groundless, so is this really the case? Let's explore the underlying reasons behind the data.

 

Initial surveyed data shows that larger number of males were infected by the novel coronavirus (SARS-CoV-2) than females. The main host receptor of SARS-CoV-2 is ACE2, which is a gene located on the X chromosome. After the initial outbreak of SARS-CoV, Stanley Perlman from the University of Iowa found that male mice exposed to SARS coronavirus are more susceptible to infection than female mice - male mice also exhibited a lower immune response, more severe lung damage, and higher mortality rate. Female mice became more likely to die when blocking estrogen or removing ovaries, while blocking testosterone in male mice had no such effect.  From the results of this experiment, estrogen could play a role in mitigating coronavirus infections to some extent. However, early reports in the literature indicate that ACE2 is highly expressed in the kidneys and testicles, which once made public believe in SARS-CoV-2 is more harmful to men than women, not only affecting the reproductive system of men, but also their infection rate. Does this mean that men are more susceptible to SARS-CoV-2 than women? 

 

With the expansion of the research scope, in April , the research team of Jining Medical University found that ACE2 was widely expressed in the ovary, uterus, vagina and placenta. This study clearly demonstrated the harm of SARS-CoV-2 to female reproductive system. Therefore, we can be sure that there is still lack in evidence to prove that the male is more susceptible to COVID-19. For men and women of the same health level, the final disease caused by viral invasion is related to various factors that mainly divided into the following categories:

 

1. Unhealthy Habits and Lifestyles - Smoking

In China, there are more males than females in cases of pulmonary infection caused by smoking, and the statistics released by cnxiangyan.com in 2018 showed that the proportion of women smoking is far fewer than men (Fig-3). Furthermore, in accordance with the article of Professor Dr. Cai Hua - professor of the University of California School of Medicine, published in Lancet this April, smoking can cause differences in SARS-CoV-2 infection between men and women.

 

Figure 3- Ratio of Male to Female Proportion Smoking in China (2018)

Statistics published by www.cnxiangyan.com

 

2. Unhealthy Habits and Lifestyles - Drinking alcohol

 

Over time and excessive alcohol use is also one of the leading causes for decreased susceptibility of humans to coronavirus. In 2016, the GBD 2016 Alcohol Collaborators - a research team formed by researchers and scientists from multiple US institutions, counted the relationship between alcohol consumption and individual health in 195 countries and regions from 1990 to 2016 and analyzed the difference in alcohol use for both sexes. According to the statistics, females consumed much less alcohol than males, not only in China, but globally, men are much more dependent on alcohol than women.

 

Figure 4- Global differences in alcohol use and dependence for females (A) and males (B)

from the year 1990 to 2016

（GBD 2016 Alcohol Collaborators, 2018)

 

3. Underlying Diseases

 

The prevalence of underlying diseases also affects the degree of infection of men and women with COVID-19. The team of Professor Li Hongliang from the Department of Cardiology of Renmin Hospital of Wuhan University (Hubei General Hospital) published an article entitled “Association of blood glucose control and outcomes in patients with COVID-19 and pre-existing Type 2 diabetes”on Cell Metabolism. The article shows that in COVID-19 cases, patients with type 2 diabetes need more medical intervention than non-diabetics patients, with a higher mortality rate, and they are more prone to develop multiple organ failure, thereby good blood glucose control plays a positive role in the prognosis of COVID-19 treatment. It also shows that patients with type 2 diabetes are facing more pressure when fighting against the invasion of SARS-CoV-2. Whether it is cardiovascular disease caused by type 2 diabetes or other factors, there are still more male patients than female patients. The article on the gender difference in cardiovascular disease in Europe published by Christina Magnussen et al in Circulation in 2017 shows this view as well.

 

Figure 5- Gender Differences in Cardiovascular Disease

(Marjan Walli-Attaei PhD et al., 2020)

 

 

In terms of hygiene habits, women value personal hygiene more than men. As one of the important instructions for the prevention of COVID-19, diligent hand hygiene will always be one of the most important defenses all of us have to reduce the risk of catching all types of infectious diseases.

 

The above analysis can explain the reason why there are more males infected with new coronavirus than women in the survey for COVID-19 research. To conclude, we cannot define the infection of SARS-CoV-2 with gender tropism unilaterally, but control and prevent the disease from more scopes. In other words, the invasion of SARS-CoV-2/coronavirus itself to the human body has no necessary connection with gender. Last but not least, all we need to bear in mind that - cherish ourselves and beloved, develop good habits.

 

References:

  1. Jiatong She, Lanqin Liu, Wenjun Liu. COVID-19 epidemic: Disease characteristics in children.Journal of medical virology. 2020;1- DOI:10.1002/jmv.25807
  1. Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention.JAMA. 2020;323(13):1239– DOI:10.1001/jama.2020.2648
  1. Yan Jing, Li Run-Qian, Wang Hao-Ran et al. Potential influence of COVIE-19/ACE2 on the Female reproductive system. Mol Hum Reprod. 2020.DOI:1093/molehr/gaaa030
  1. Magnussen C, Niiranen TJ, Ojeda FM, et al. Sex Differences and Similarities in Atrial Fibrillation Epidemiology, Risk Factors, and Mortality in Community Cohorts: Results From the BiomarCaRE Consortium (Biomarker for Cardiovascular Risk Assessment in Europe).Circulation. 2017;136(17):1588‐ DOI:10.1161/CIRCULATIONAHA.117.028981
  1. Cai H. Sex difference and smoking predisposition in patients with COVID-19. Lancet Respir Med. 2020;8(4):e20. DOI:10.1016/S2213-2600(20)30117-X
  1. CDC COVID-19 Response Team. Coronavirus Disease 2019 in Children - United States, February 12–April 2, 2020. 69 (14); 422–426 Morbidity and Mortality weekly report.
  1. China CDC. COVID19, 2020. Chinese Center for Disease Control and Prevention. Retrieved from: http://www.chinacdc.cn/en/COVID19/
  1. Wang A, Zhao W, Xu Z, Gu J. Timely blood glucose management for the outbreak of 2019 novel coronavirus disease (COVID-19) is urgently needed.Diabetes Res Clin Pract. 2020;162:108118. DOI:10.1016/j.diabres.2020.108118
  1. Peter P. Liu, Alice Blet, David Smyth, Hongliang Li. The Science Underlying COVID-19: Implications for the Cardiovascular System. Circulationha. 2020. DOI:1161/CIRCULATIONAHA.120.047549
  1. Caibin Fan, Kai Li, Yanhong Ding, Wei Lu Lu, Jianqing Wang. ACE2 Expression in Kidney and Testis May Cause Kidney and Testis Damage After 2019-nCoV Infection. medRxiv2020;20022418; DOI: https://doi.org/10.1101/2020.02.12.20022418
  1. GBD 2016 Alclhol Collaborators. Alcohol use and burden for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2018. 392(10152):1015-1035; DOI:https://doi.org/10.1016/S0140-6736(18)31310-2
  1. Marjan Walli-Attaei PhD, Philip Joseph MD, Prof Annika Rosengren MD et al. Variations between women and men in risk factors, treatments, cardiovascular disease incidence, and death in 27 high-income, middle-income, and low-income countries (PURE): a prospective cohort study. Lancet. 2020.DOI: https://doi.org/10.1016/S0140-6736(20)30543-2

  

Cyagen is opening orders on models for ACE2 receptor targets, including humanized, knockout (KO), and ROSA26 knockin (KI) mouse models.

For more information, visit ACE2 Mice – Expedite Your COVID-19 Research Efforts.

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