In the last six months, the world has learned that the SARS-CoV-2 virus, more commonly known as COVID-19, is contagious, can be deadly, and has become a global pandemic. As of today, more than 8.2 million people have tested positive, and more than 445,000 have died worldwide from COVID-19. There is still much we do not know about this virus. What we do know is that the elderly are disproportionately affected, as are ethnic minorities and those with underlying health conditions, including hypertension, diabetes, ischemic heart disease, obesity, and chronic lung disease.
But could our genes factor into who gets COVID-19, who gets sick or dies from the condition, and who does not? Preliminary data from several early studies now point to yes.
The first genetic association emerging concerns the relationship between blood type and COVID-19. Blood types are inherited from both biological parents. There are four major blood groups determined by the presence or absence of two antigens (A and B) on the surface of our red blood cells. There is also a protein, called Rh Factor, that is present (+) or absent (-). Together, these factors create the eight most common blood types (A+, A-, B+, B-, O+, O-, AB+, AB-). Of these, the two most common blood types in the U.S. are O+ (37%) and A+ (35%), with prevalence varying moderately in different parts of the world.
Preliminary data published from Wuhan, China in March 2020 indicated that people with type A blood appear to be at higher risk (Overall Risk (OR) = 1.21) to develop COVID-19 than people with other blood types. It also appeared that people with type O blood were at lower risk (OR 0.67) to develop COVID-19, compared to people who do not have type O blood. This means that someone with type A blood has 1.21 times the overall risk of getting COVID-19 as a person without type A blood. It also means that someone with O blood has .67 times the risk of developing COVID-19 as a person without type O blood.
The general trend of a higher COVID-19 risk for A blood types and a lower risk for O blood types has now been described in preliminary studies from COVID-19 patients in Italy and Spain, the United Kingdom, and New York. There is also evidence to indicate that people with AB and B blood types have a higher risk of COVID-19 infection, but these associations did not reach statistical significance, meaning the trend may have been due to chance versus an actual association. Importantly, it appears that these findings may only be significant in Rh+ blood types, although more data are needed. Blood type does not appear to predict the severity of a COVID-19 infection. We are all still learning, and more research is needed to confirm and clarify these associations.
The association between blood type and infectious disease risk is not a new one. Previous data have indicated that viral infection susceptibility for Hepatitis B, SARS, and other infections differs depending on blood type.
A second genetic association may be between COVID-19 and the APOE gene. APOE stands for “apolipoprotein E.” This gene plays a role in maintaining normal blood levels of cholesterol and other fats and is important for keeping neurons in the brain healthy. There are three versions of the APOE gene: e2, e3, and e4. Everyone has two copies of the APOE gene, one inherited from each parent, with six possible gene copy combinations or genotypes (e2/e2, e2/e3, e2/e4, e3/e3, e3/e4, e4/e4). Inheriting one or two copies of the e4 version of the APOE gene is associated with an increased risk of dementia, particularly when someone inherits two copies (e4/e4). Dementia is a common condition seen with COVID-19, and people who have both dementia and at least one copy of the e4 version of the APOE gene are at higher risk to die of COVID-19.
One study examined the association between APOE e4 and COVID-19 in hospital patients from the UK Biobank who tested positive for the virus between March 16 and April 26. People with two copies of the e4 version of the APOE gene were more likely to test COVID-19+ (OR=2.31) compared to those who had two copies of the e3 version of the APOE gene. This was true even after removing participants with conditions linked to COVID-19, such as dementia, hypertension, coronary artery disease, and type 2 diabetes. Having two copies of the e4 version of the APOE gene has previously been associated with increased risk of viral, bacterial, and parasitic infections and is being questioned as a predictor of COVID-19 severity as well.
Several of these studies have yet to undergo peer review, meaning they should be considered preliminary, and all of these findings require further investigation. Many of these studies include small numbers of patients that only provide a snapshot of how the COVID-19 pandemic has affected patients in one hospital system or one area of the world. For these reasons, it would be premature to use this information to guide current decision-making.
However, if these associations are verified by future studies, this genetic information may help guide clinical care, and even re-openings, as we move forward. For instance, it is possible that people with A+ blood type and/or two copies of the e4 version of the APOE gene may be at greater risk and may require greater protection from exposure. In order to further understand these and other genetic associations, we should consider adding some baseline genetic testing to COVID-19 testing, so we can better predict who is at greatest risk to get this virus and who is at greatest risk to become very ill or die from COVID-19.