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.
TopUnderstanding The Non-Randomness Of The Covid-19 Pandemic
In a “classical” model for understanding non-randomness of epidemies three main groups of factors apply, namely the environmental, the host factors (human) and the agent factors (SARS-CoV-2)(What Is the Epidemiologic Triangle?, n.d.).
The environmental factors, includes a broad specter of parameters like socioeconomic measures, climate, UV radiation, pollution, population density, communication, cultural and behavioral parameters. Thus the degree of severity of a pandemic will also depend on the society's possibility for allocation of resources through health care, finances, restructuring and level of knowledge(COVID-19 pandemic, n.d.; Hossain et al., 2020; Kumar et al., 2021). In the COVID 19 pandemic, surveillance and high standards of public health measures did not prevent the pandemic from affecting the western part of the world and the high-income countries during the first wave of the pandemic.
The second dimension is the host side, meaning the individual as the recipient of the disease. This may, for example, be in the form of vulnerability in predisposing root diseases, age, sex, the ability of the body to respond adequately to an infection and hereditary predispositions in the recipient. Male mice studies indicate genetic variations in the chromosome Y to regulate susceptibility to influenza A virus infections. The influence of sex hormones on the immune system has gained growing interest(Krementsov et al., 2017). Here we hypothesize genetic androgen variations in the Y chromosome to affect the outspread and outcome of the COVID 19 disease.
The third dimension is the agent or pathogen, such as the virus or bacterium with its causative properties and the ability to mutate and interact with the host or recipient; here pathogenicity (infectivity) of the microbe. The SARS-CoV-2 virus constantly mutate and multiple variants of the virus has appeared during the pandemic(Biswas & Mudi, 2020). In this context genetic variations of the virus possibly affecting different Y -haplogroups with variable interacting severity, would be of great importance for further studies.
During the ongoing pandemic of COVID-19, these dimensions have been approached and emphasized differently in different countries.