Sexual dimorphism in patients with COVID-19: Review

Abstract

The world is facing its biggest global crisis in the1 form of the nCoV-19 pandemic. Females have long been supposed to have stronger immunity against all diseases including the viruses and nCoV-19 seems to be part of a larger spectrum. The causes of less prevalence and mortality rates in females could range from a multitude of factors like stronger innate immunity to sex chromosomes to steroid hormones. Females under being diploid X chromosome undergo XCI which leads to varied manifestations of many immunomodulatory genes. The lower prevalence of COVID-19 in females could be attributable to lesser ACE2 receptors, biallelic expression of TLR7, Ddx3x, CD40L and CXCR3, higher IFN’s, exaggerated expression of NEMO, IRAK1, JAK-STAT pathway, the higher number of macrophages, enhanced Th1 response and higher circulating antibodies in females. The major causes of death in a COVID-19 case has been reported to be ARDS, hypokalemia, respiratory failure, and multiorgan failure due to immune dysfunction. The increased expression of IL-6, CXCL-10, MCP-1, MIP-1α, CCL-14, and CCL-23 appear to tilt the balance in males towards an increased N/L Ratio leading to cytokine storm and ACE2 down-regulation progressing to hypokalemia, hypotensive shock and ARDS. Apart from the various protective effects existing in females in preventing the above complications, there is an upregulation of P53 and FOXP3 gene and a pro-apoptotic response which increases the Treg cells trying to bring back the female body to homeostasis.