I have to start out by saying that I’ve hesitated to do this write up for over a month now. Mostly because there is still so much we don’t know about the novel Coronavirus; however we do already know a lot about how our genetics play a role in how susceptible we are to developing certain health problems, and also our ability to fight viral infections. The strong genetic link of this virus could not be more evident in one family as it is in the Fusco family, from New Jersey. Rita Fusco-Jackson, 56, passed away from COVID-19 on March 13th, her brother Carmine Fusco died on March 18th, mere hours before their Mother Grace Fusco, 73 also succumbed to the virus. Then the following day Vincent Fusco(brother & son), 53 also passed away from the novel virus. Shockingly, this is not the only case of multiple deaths reported in one biological family. The WHO (World Health Organization) claims the mortality rate of COVID-19 is approximately 3.4%. For comparison SARS (Severe Acute Respiratory Syndrome) had about a 10% mortality rate, MERS (Middle East Respiratory Syndrome) had a 35% mortality rate. So how is it possible that something with an overall 3.4% fatality rate has such a high incidence of poor outcomes among biological family members? This is where our Genetics come into play.
Before we get into specific genetic variations that can affect viral susceptibility we need to go over the basics. Let’s think of DNA (DeoxyriboNucleicAcid) as an instruction manual for our bodies. This is created with very long chains of building blocks we call bases. These bases collectively are: Adenine (A), Guanine(G), Thymine (T), and Cytosine (C). Like with any manual there can be “typos” or a printing error. Most of these typos have no inimical effects on our cells..however, some of these “printing errors” can impact the function of the protein made from a gene…these “typos” are called mutations.
“The DNA of all humans is 99.5% identical...that 0.5% difference is where you will find your genetic variants. These genetic variations contribute to everything from your eye color, your blood type, and a small percentage are even linked to disease. In that 0.5% you will find millions of variants. Most variants occur in DNA sequences found outside of the genes...however, some do occur inside the genes. ”
Now let’s dive into the genetic variants that potentially impact COVID-19 susceptibility…
In order for COVID-19 to get inside our cells, the virus latches onto the protein, ACE2. The gene ACE (angiotensin-converting enzyme) is found in the small intestine and the lungs, as well as some cells. Past studies have found variations in the ACE2 gene are known to make people more susceptible to the coronavirus SARS-CoV.
The TMPRSS2 gene encodes an enzyme called Transmembrane Protease Serine 2. TMPRSS2 activates the spike protein seen in human coronaviruses, such as SARS-CoV and MERS-CoV. SARS-CoV-2 uses ACE2 as a means of entry and then uses TMPRSS2 for S protein priming.
The ABO gene determines a person’s blood type. Some scientists have reported a higher risk for acquiring COVID if you have blood group A; and a lower risk associated with those who have blood type O.
The MBL2 gene (Mannose-binding lectin) is part of the immune system that recognizes carbohydrate signatures from foreign pathogens.
The CCL2 gene is located on the 17th chromosome and is involved in the recruitment of monocytes and other immune system cells needed at the site of an inflammatory response.
The OAS1 gene is located on chromosome 12 and is induced by interferons and encodes a protein. The OAS1 protein activates an enzyme that degrades viral RNA and inhibits the replications of the virus. Interferons are the first wave of defenders when it comes to viral infections. They are considered cytokines that signal to other cells to protect against the spread of the virus.
The MX1 gene is an interferon induced GTP binding protein. It’s found on the 21st chromosome and is responsible for antiviral activity against a wide range of RNA viruses and even some DNA viruses.
Chromosome 4 is where you’ll find the TLR3 gene. The protein that is encoded by this gene belongs to the Toll-Like Receptor (TLR) family. This plays a crucial role in the recognition of pathogens and the activation of inherent immunity. They recognize pathogen-associated molecular patterns (PAMPS) that are asserted on infectious agents, and intercede the production of cytokines necessary to the advancement of effective immunity.
CCR5 (C-C Chemokine Receptor Type 5) this is a protein located on the surface of white blood cells that is directly involved in the immune system because it acts as chemokine receptor. It has been shown that carriers of a specific mutation of this gene are resistant to HIV infection.
There are variants in a gene called HBB that contain instructions for making the hemoglobin protein that carries oxygen inside our red blood cells. This variant can make people less susceptible to an infectious disease such as malaria. I think it’s important to note however that many genetic variants that offer beneficial protection can also increase your risk for certain genetic disorders. In the case of HBB those disorders are Sickle-cell disease and Beta Thalassemias.
