Dr. Muhammad Torequl Islam :
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) utilizes angiotensin-converting enzyme II receptor (ACE2R) to entry into the lung alveolar epithelial cells. ACE2 also plays a vital role in lung protection. It has been seen that among the entire population, 58% are males in novel coronavirus disease 2019 (Covid19). Many reasons, such as outer activities and lifestyle, concurrent diseases, host immune power and other pathophysiological events may link behind this fact. It has been also reported that the differential expression of ACE2 in different ages among these two classes of human may affect the severity of SARS-CoV-2 infections. Under normal conditions, no sex differences in ACE2 activity have been evident in the heart and lung of experimental animals. Therefore, this virus will affect equally the male and female. It should be mentioned that the ACE2 expression in third gender is yet to be found out along with the prevalence of Covid19. In a pre-clinical study, a decrease in ACE2 content was seen in young-adult and middle-aged group (by 25% in male and 18% in female, respectively) rats. In this study, a significant high ACE2 content was detected in old female animals than male. One study reports a significant low ACE serum activity in older men (>55 yrs) compared to women (both younger and older) and younger men. In women, a significant high ACE2 serum activity was also observed in older women than the younger ones. It has been seen that the death rate between 20 to 39?yrs. (younger age) of females is more than the older females and the same age range of males.
Estrogen (also called oestrogen), the primary female sex hormone which is known for its anti-inflammatory effects on human. Estrogen or estrogenic compounds (e.g., 17ß-estradiol) is evident to reduce influenza A virus replication in primary human nasal epithelial cells derived from female. In the respiratory virus infected experimental animals (mice), a weaker estrogen receptor signaling has been documented with the increased morbidity and mortality in both males and females. Estrogen (estradiol 100 micrograms/day for 7 days through a patch applied to the skin) is under phase 2 clinical trial of 110 participants. On the other hand, progesterone-based contraceptives have been found to reduce adaptive immune responses and protection against sequential influenza a virus infection. This hormone (progesterone 100 mg will be administered subcutaneously twice daily for 5 days in addition to institutional standard of care) is also under phase 1 clinical trial of 40 participants. In a study, a higher renal ACE2 activity was observed in male mice than females. It was also demonstrated that the lower ACE2 may be due to the effects of the ovary and to the presence of 17ß-oestradiol in female animals. In contrary, Vignera and his co-workers (2020) have been reported that 17ß-oestradiol increases the expression and activity of ACE2 in both adipose tissue and kidney. They have also demonstrated that the hypertensive male animals have a higher myocardial ACE2 expression than females.
Luteinizing hormone (LH) stimulates ovaries to produce estrogen and progesterone. However, around age 50, women’s ovaries reduce producing decrease amounts of estrogen and progesterone. The pituitary gland tries to compensate by producing more follicle-stimulating hormone (FSH). LH has a direct stimulatory effect on the immune system. Similarly, FSH affects lymphocyte proliferation and interleukin (IL)-6 production. Generally, a weaker immune system makes it harder for older adults to fight off infection. Females have higher adiposity and obesity prevalence, however, they are generally protected from obesity-related metabolic and cardiovascular complications produced by angiotensinogen, renin, and angiotensin II.
On the other hand, the male hormone testosterone at a normal circulating level exerts protective effects on the respiratory system as it can improve the forced expiratory volume in one second and forced vital capacity. Testosterone also reduces inflammation through downregulating some important pro-inflammatory cytokines, including IL-1-beta, -6, and tumor necrosis factor (TNF)-alpha. The SARS-CoV-2 infection results a hyperinflammatory condition in which the immune system of a patient responds too aggressively leads to an enormous immune response (cytokine storm). This may lead to severe lung damage, acute respiratory distress syndrome (ARDS) and even death. A low plasma testosterone concentration is related to older age and associated with some comorbidities, such as obesity, diabetes and obstructive sleep apnea. The transmembrane protease serine 2 (TMPRSS2) cleaves ACE2 for augmented viral entry, which is essential for viral spread and pathogenesis in the infected person. Testosterone modulates TMPRSS2 gene expression, which has been suggested to contribute to the predominance of Covid19 in human.
In women, testosterone is produced in various locations, such as ovary (25%), adrenal gland (25%), and 50% is produced in the peripheral tissues from the various precursors produced in the ovaries (from androstenedione, during pregnancy) and the adrenal gland. A decreased testosterone level is found in both pre- and post-menopausal women. Therefore, the women having adequate level of testosterone may receive an advantage over others having a low serum level of this hormone in Covid19. However, the SARS-CoV-19 infection pattern, severity, and comorbidity in women are yet to be found out.
(Dr. Muhammad Torequl Islam is Assistant Professor, Department of Pharmacy, Bangabandhu Sheikh Mujibur Rahman Science and Technology University. E-mail: [email protected])
