Monday, November 30, 2020

The genetics of susceptibility to COVID-19

Left: Frequency of an rs2258666 allele in Indian populations (TT-plus strand or AA-minus strand). Right: COVID-19 case-fatality rate (August 2020).



ACE2 is a cell receptor that mediates the infection of lung tissue by coronaviruses, either the one that causes COVID-19 or others that cause the common cold. The ACE2 gene has 1,700 alleles, some of which are associated with increased susceptibility to coronavirus infection (Frost 2020).


This difference in susceptibility has been shown in a recent Indian study (Srivastava et al. 2020). COVID-19 is most fatal in the western states of Gujarat, Maharashtra, Madhya Pradesh, and Punjab. Conversely, it is least fatal in the northeast states of Assam, Arunachal Pradesh, and Nagaland. This pattern closely correlates with genetic variation at the rs2285666 locus of ACE2. The presence or absence of a single allele explains 35% of the variation in the COVID-19 case-fatality rate.


The authors conclude that some kind of selection has been acting on rs2285666. If we look at the map, susceptibility to COVID-19 seems to be strongest in those regions with the longest history of sedentary living and large urban centers. Conversely, it seems to be weakest in the Northeast, which is home to people who, until recent times, belonged to small communities that routinely moved from one cultivable area to another.


These findings are consistent with the hypothesis that the ACE2 receptor has coevolved with human environments. Because respiratory viruses boost the immune response of lung tissue and thereby prevent more serious pulmonary diseases (e.g., tuberculosis, pneumonia, pneumonic plague), some human populations may have gained protection from severe respiratory infections by becoming more susceptible to mild respiratory infections, such as those normally caused by coronaviruses. This commensal relationship would have been especially adaptive where respiratory pathogens could easily propagate, that is, in crowded environments where many people live in proximity not only to each other but also to livestock. In regions that have long had crowded environments, natural selection may have favored susceptibility to infection by coronaviruses, which are normally mild in their effects, as a means to maintain a strong immune response to deadly pulmonary diseases (Frost 2020).





I'm sorry for the break in my posting. When the pandemic first struck, I expected to have a lot of time on my hands, so I began a series of writing projects: four articles and a manuscript for a book. Unfortunately, my free time dried up over the summer, and my workload became overwhelming. I hope I've now found the right balance between my writing projects and my regular work.




Frost, P. (2020). Does a commensal relationship exist between coronaviruses and some human populations? Journal of Molecular Genetics 3(2): 1-2.


Srivastava, A., A. Bandopadhyay, D. Das, R.K. Pandey, V. Singh, N. Khanam, N. Srivastava, P.P. Singh, P.K. Dubey, A. Pathak, P. Gupta, N. Rai, G.N.N. Sultana, and G. Chaubey. (2020). Genetic Association of ACE2 rs2285666 Polymorphism with COVID-19 Spatial Distribution in India. Frontiers in Genetics. September 25