• Dr. Therese Ann Markow

Op-Ed: The other side of the coin…COVID-19 resistance, susceptibility, and outcome

People wonder why some people, despite close and even intimate contact with a gravely ill COVID-19 patient, never get sick? The answer to this question could point to new vaccine and treatment approaches. In this lucky subpopulation some people never test positive for COVID-19 and some that test positive never develop any symptoms. These observations suggest two things: that some people have some innate resistance that prevents the virus from entering them, and others, while the virus gets in, and they test positive, never develop symptoms. What’s up with this?

Genetic studies are turning up some interesting answers. A study published last year by Dr. Christopher Latz and others at Massachusetts General Hospital revealed an association between blood type and disease susceptibility: people with type O blood seemed less susceptible than those with type A. Disease outcomes, however, were unaffected1. A review by Dr. David Robertson and colleagues in the UK summarizes the how the virus itself attacks human cells and how the mutant strains that are becoming dominant have changed in their potential to infect and cause illness2. But it takes two to tango. There’s a host, or human aspect to this as well, since clearly people differ in their responses after being exposed to the virus. We know there are predisposing factors, such as obesity, diabetes, heart disease, and general lifestyle. But hereditary factors, apart from these pre-existing conditions, play a role. Now, with thousands of cases to examine, more powerful genomic studies can be undertaken looking at the role of the human genotype in this host-pathogen interaction. The other side of the coin.

One obvious place to look was the ACE2 (angiotension converting enzyme-2) gene because it codes for the cell surface receptor where the virus spike protein binds. It turns out, in fact, Dr. Birte Möhlendickthat and co-investigators in Germany found that the gene coding for this receptor includes variants that differ among infected and uninfected individuals3. Finally, a broader study by the COVID-19 Host Genetics Initiative, using thousands of whole genomes, revealed 13 genes as having strong associations with 1. disease susceptibility and/or 2. disease severity4. The majority of the genes were connected to lung function and to the immune system.

​Clearly there is an interaction between the virus genotype and that of the host. The interaction can determine the outcome of virus exposure, the difference between health or illness and even death. These exciting findings point the way to developing better preventions and personalized treatments.

Therese Ann Markow

Professor Emerita

Division of Biological Sciences

University of California at San Diego

1 Annals of Hematology (2020) 99: 2113–2118.

2 Nature Reviews Microbiology (2021) 19:409–424

3 Pharmacogenetics and Genomics (2021) 31:165-171

4 Nature (2021) July 8

Editors note:

"Dr. Therese Markow is an award-winning geneticist who has held endowed professorships at major universities in the United States, as well as positions abroad. She now turns her attention to connecting with a broader audience, by having critical discussions, in everyday language, about issues that impact our health, our society, and our planet within her weekly podcast, Critically Speaking."

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