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A Phylogenetic Approach to the Uneven Global Distribution of the COVID-19 Pandemic: Y-Chromosomal Haplogroups and COVID-19 Mortality
Abstract
A possible role of Y chromosomal haplogroups in COVID-19 mortality is discussed without claiming causality. The mortality of COVID-19 seems unequally distributed in different populations and statistically significant regional covariation is presented between COVID-19 mortality and the haplogroup Y-R1b. Y-R1b is suggested as a possible marker for mortality in the first wave of the pandemic affecting the Western Europe. September 2020 the pandemic involved also Eastern Europe severely in a second wave, while South East Asia, with a very high frequency of Y-0, had strikingly low COVID-19 mortality rate. Eastern Europe is dominated by Y-haplogroups (i.e., Y-R1a), with close ancestry to Y-R1b. Molecular mechanisms mediated by the Y chromosome involved in COVID-19 mortality are discussed, presenting a possible role of KDM5D in androgen receptor modulation and regulation of TMPRSS2 known to enable SARS-CoV-2 binding to ACE2 and facilitating virus entrance into the cell and virus replication. Sex bias and comorbidities point at the role of variations in the Y-chromosomal phylogeny.
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