Gender and Age Differences Reveal Risk Patterns in COVID-19 Outbreak

Yogendra Singh, MPharm; Gaurav Gupta, PhD; Anurag Mishra, PhD; Dinesh Kumar Chellappan, PhD; Kamal Dua, PhD

Download the pdf

ABSTRACT
By April 28th 2020, the global number of people that were viciously infected with the newfound novel corona virus (COVID-19) stood at a staggering 3 077 133 cases, as per the confirmed data released by the WHO. It has been reported that women from the Chinese Han population are associated with essential hypertension due to their relation with the 5 SNPs, namely, rs1514283, rs4646155, rs4646176, rs2285666, and rs879922, which belong to the ACE2 gene. The level of ACE2 activity was very low in normal healthy younger persons, and was reported to be increased in patients with cardiovascular diseases. Thus, there might be severe myocarditis, that may result in acute heart failure and cardiac complexities in the elderly subjects. (Altern Ther Health Med. 2020;26(S2):54-55)

Yogendra Singh, MPharm, Mahatma Gandhi College of Pharmaceutical Sciences, Sitapura, Jaipur, India. Gaurav Gupta, PhD; and Anurag Mishra, PhD, School of Pharmacy, Suresh Gyan Vihar University, Mahal Road, Jagatpura, Jaipur, India. Dinesh Kumar Chellappan, PhD, Department of Life Sciences, School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur, Malaysia. Kamal Dua, PhD, Lecturer, Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney (UTS), Ultimo, NSW, Australia; Visiting Researcher, Center for Inflammation, Centenary Institute, Sydney; and Conjoint Lecturer, School of Biomedical Sciences and Pharmacy, The University of Newcastle (UoN), Callaghan, Australia

Corresponding author: Gaurav Gupta, PhD
E-mail address: [email protected]

In December 2019, a global pandemic started in Wuhan, China, related to the novel coronavirus 2019-nCoV or COVID-19, which is caused by the severe acute respiratory syndrome (SARS) coronavirus 2 (CoV-2). As of April 28, 2020, health authorities had reported 3 077 133 cases and 211 961 deaths globally.

This new betacoronavirus resembles the coronavirus SARS-CoV and the Middle East respiratory syndrome coronavirus (MERS-CoV), being genetically similar to them. It possibly came from a bat-generated coronavirus that had spread to people from an unknown intermediate mammal host. SARS-CoV-2’s viral genome was quickly sequenced for use in diagnostic tests, epidemiological follow-ups, and development of preventive and therapeutic strategies.

Recent findings from 2 recent papers published in The Lancet have revealed firsthand information on the infection’s nature and characteristic features.^1,2 Both studies were conducted at the Jin Yin-Tan hospital in Wuhan, with one study being prospective and the other retrospective. The 2 studies included 140 patients and intended to examine various interrelated parameters to develop firsthand evidence related to epidemiology, radiology, clinical features, laboratory data, and outcomes.

The demographic data from both studies revealed that most of the infected patients were men, 30 out of 41 (73%) in the prospective study and 67 out of 99 (67.67%) in the retrospective study, with the average ages in the groups being 49 and 55 years, respectively.

Compared to the fatality rate for young healthy individuals and elderly women (age greater than 50 y) who had contracted the virus, the two studies found a relatively higher mortality rate for elderly men (age greater than 50 y) who had underlying conditions. These data provide clues to factors that influence mortality: age and gender.

On January 3, 2020, medical authorities identified 2019-nCoV in samples of bronchoalveolar lavage fluid from a patient in Wuhan, which was eventually confirmed as the cause of the person’s pneumonia. In terms of pathogenic severity, 2019-nCoV seems to have a similar impact to that of SARS-CoV and MERS-CoV.³ Predictive bio-informatic methods and in-vitro testing have shown that high levels of human angiotensin-converting enzyme 2 (ACE2) is the presumptive receptor for entry into host cells.^4-6 ACE2 is predominantly present in the lungs and kidneys.

Gender differences determine and aging alters the biochemical behavior of the human body. A clinical study by Fernández-Atucha et al comprised 118 participants who were normal and healthy, with no history of cardiovascular conditions.7 The study included 60 males with an average age of 56.58 ± 6.47 years and 58 females with an average age of 54.47 ± 4.99 years. Participants ranged in age from 41 to 70 years. They had no proliferative conditions or diseases of the nervous system.

The study further demonstrated the effects of gender differences and age with respect to the function of the renin–angiotensin system serum peptidases. The behavioral pattern of the gonadal hormones, namely, estrogen and testosterone in elderly were also influenced due to ageing. Although, the levels of estrogen decrease, the level of testosterone increased ACE activity.

Another study in 2006, called the Massachusetts Male Aging Study (MMAS), found a reduction in the levels of testosterone in 21% of men who were 55-59 years old and in 26% of men who were 60-69 years old.⁸ The percentage rose to 31% for men 70 to 86 years old. Moreover, the level of ACE2 increased due to a decrease in the ACE serum activity, which was caused by a decrease in the level of testosterone in males. In contrast, estrogen participates in the upregulating of the expression of ACE2.⁹ Loss of estrogen activity in the postmenopausal period can cause a decrease in the ACE2 activity level in females.¹⁰

One study found that women from the Chinese Han population are associated with essential hypertension due to their relation with the 5 SNPs, namely, rs1514283, rs4646155, rs4646176, rs2285666, and rs879922, which belong to the ACE2 gene.¹¹ The study also found that the level of ACE2 activity was very low for normal, healthy, younger individuals (age less than 49 y)  and increased in patients with cardiovascular diseases. Thus, severe myocarditis may be present in elderly (age greater than 50 y) individuals with severe COVID19 that can result in acute heart failure and cardiac complexities. In addition, it’s also common to have an acute kidney injury. This might have resulted from a disturbance in the ACE2 level due to binding of COVID-19 with it.

The above results may help predict the risk pattern associated with age and gender for individuals infected by the novel coronavirus.

Authors’ disclosure statement

The authors declare that they have no conflict of interest

References

1. Huang C, Wang Y, Li X et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. Feb 2020; 395(10223):467-536, e28-e32.
2. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. The Lancet. Feb 2020; 395(10223):507-513.
3. Zhu N, Zhang D, Wang W, et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N Engl J Med. 2020; 382:727-733.
4. Zhou P, Yang X-L, Wang X-G, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020 Mar; 579(7798):270-273..
5. Xu X, Chen P, Wang J, et al. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Science China Life Sciences. 2020 Mar; 63(3):457-460.
6. Letko M, Munster V. Functional assessment of cell entry and receptor usage for lineage B β-coronaviruses, including 2019-nCoV. bioRxiv. 2020. 2020.2001.2022.915660.
7. Fernández-Atucha A, Izagirre A, Fraile-Bermúdez AB, et al. Sex differences in the aging pattern of renin–angiotensin system serum peptidases. Biology of Sex Differences. 2017; 8(1):5.
8. Hilliard LM, Sampson AK, Brown RD, Denton KM. The “his and hers” of the renin-angiotensin system. Current Hypertension Reports. 2013; 15(1): 71-79.
9. Singh, Y., Singh, K. & Sharma, P.L. Effect of combination of renin inhibitor and Mas-receptor agonist in DOCA–salt-induced hypertension in rats. Mol Cell Biochem 373, 189–194 (2013). https://doi.org/10.1007/s11010-012-1489-2
10. Bukowska A, Spiller L, Wolke C, Lendeckel U, Weinert S, Hoffmann J, Bornfleth P, Kutschka I, Gardemann A, Isermann B, Goette A. Protective regulation of the ACE2/ACE gene expression by estrogen in human atrial tissue from elderly men. Exp Biol Med (Maywood)2017 Aug; 242(14): 1412–1423. Published online 2017 Jun 29. doi: 10.1177/1535370217718808v
11. Zhang Q, Cong M, Wang N, et al. Association of angiotensin-converting enzyme 2 gene polymorphism and enzymatic activity with essential hypertension in different gender: A case-control study. 2018; 97(42): e12917.