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2020 ; 21
(10
): ä Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
COVID-19 and Individual Genetic Susceptibility/Receptivity: Role of ACE1/ACE2
Genes, Immunity, Inflammation and Coagulation Might the Double X-chromosome in
Females Be Protective against SARS-CoV-2 Compared to the Single X-Chromosome in
Males?
#MMPMID32423094
Gemmati D
; Bramanti B
; Serino ML
; Secchiero P
; Zauli G
; Tisato V
Int J Mol Sci
2020[May]; 21
(10
): ä PMID32423094
show ga
In December 2019, a novel severe acute respiratory syndrome (SARS) from a new
coronavirus (SARS-CoV-2) was recognized in the city of Wuhan, China. Rapidly, it
became an epidemic in China and has now spread throughout the world reaching
pandemic proportions. High mortality rates characterize SARS-CoV-2 disease
(COVID-19), which mainly affects the elderly, causing unrestrained
cytokines-storm and subsequent pulmonary shutdown, also suspected micro
thromboembolism events. At the present time, no specific and dedicated
treatments, nor approved vaccines, are available, though very promising data come
from the use of anti-inflammatory, anti-malaria, and anti-coagulant drugs. In
addition, it seems that males are more susceptible to SARS-CoV-2 than females,
with males 65% more likely to die from the infection than females. Data from the
World Health Organization (WHO) and Chinese scientists show that of all cases
about 1.7% of women who contract the virus will die compared with 2.8% of men,
and data from Hong Kong hospitals state that 32% of male and 15% of female
COVID-19 patients required intensive care or died. On the other hand, the
long-term fallout of coronavirus may be worse for women than for men due to
social and psychosocial reasons. Regardless of sex- or gender-biased data
obtained from WHO and those gathered from sometimes controversial scientific
journals, some central points should be considered. Firstly, SARS-CoV-2 has a
strong interaction with the human ACE2 receptor, which plays an essential role in
cell entry together with transmembrane serine protease 2 (TMPRSS2); it is
interesting to note that the ACE2 gene lays on the X-chromosome, thus allowing
females to be potentially heterozygous and differently assorted compared to men
who are definitely hemizygous. Secondly, the higher ACE2 expression rate in
females, though controversial, might ascribe them the worst prognosis, in
contrast with worldwide epidemiological data. Finally, several genes involved in
inflammation are located on the X-chromosome, which also contains high number of
immune-related genes responsible for innate and adaptive immune responses to
infection. Other genes, out from the RAS-pathway, might directly or indirectly
impact on the ACE1/ACE2 balance by influencing its main actors (e.g., ABO locus,
SRY, SOX3, ADAM17). Unexpectedly, the higher levels of ACE2 or ACE1/ACE2
rebalancing might improve the outcome of COVID-19 in both sexes by reducing
inflammation, thrombosis, and death. Moreover, X-heterozygous females might also
activate a mosaic advantage and show more pronounced sex-related differences
resulting in a sex dimorphism, further favoring them in counteracting the
progression of the SARS-CoV-2 infection.