How Population Genomics Research Has Advanced Knowledge About COVID-19 Host Genetics

MUSC has partnered with Helix, a leading population genomics company, to help create the new In Our DNA SC community health research program. 

While participating in population health projects helps advance current research, it also can establish a large database that can be rapidly called upon when we need to learn about something new, like COVID-19. 

During the COVID-19 pandemic, Helix already had a large consented research community from their internal research program and collaborations with other health systems, enabling them to be in a position to rapidly learn about how DNA may affect COVID-19 susceptibility by combining genomic data with medical and voluntary COVID-19 survey data. In collaboration with other research groups around the world, this research community allowed scientists to discover genetic factors that may slightly affect a person's likelihood of experiencing severe COVID-19 or experiencing more intense side effects from vaccines. 

Thanks to collaborative participation, Helix’s research community has contributed to numerous advances in the scientific understanding of COVID-19 host genetics, including learnings from the following studies:

How DNA may influence a person’s vulnerability to severe COVID-19 

Helix sent out a survey to their research community asking about their exposure to COVID-19, whether they had been tested, what symptoms they may have been experiencing, and related information. These data were then paired with each respondent’s genetic data and used by researchers who were looking for patterns that may suggest an association between genetic factors and vulnerability to severe COVID-19.

These data have led to numerous publications, including one generated with a team of researchers from around the world who collaborated with Helix scientists. Together, the team found that people who developed severe symptoms of COVID-19 tended to have variations in their DNA sequence that occurred in the same part of the DNA. It’s not clear yet how changes to the DNA sequence in this location could affect a person’s response to COVID-19 infection, but it may have to do with immune cells.

This finding has since been replicated in numerous studies, suggesting that something about this part of DNA is important. 

The next big finding came in September 2020, through another collaboration with researchers from around the world which revealed that alterations in the DNA that affect the body’s innate immune response could be responsible for as much as 3.5% of severe COVID-19 cases. In other words, changes to the DNA that decrease the body’s ability to mount a rapid response to the virus seem to have caused many people to develop severe symptoms. Had their body been able to respond to the virus quickly, they might have only developed mild symptoms (if any at all). 

This finding marked the first time scientists had been able to identify a location in the DNA that is not only associated with severe COVID-19, but they had evidence to show that it was likely causing severe COVID-19. 

Narrowing in on the symptoms of COVID-19 

It has been useful at various points of the pandemic to identify people who likely had COVID-19 based on their symptoms. This is a difficult task, though, because the list of symptoms associated with COVID-19 is long, evolves with new SARS-CoV-2 variants, and is not very unique—many of the symptoms overlap with other conditions, such as the common cold. 

In a paper that Helix published as a pre-print in December 2020, scientists outlined symptoms of COVID-19 and their enduring nature. Among the findings were two big insights: That researchers need to consider the number of initial symptoms when studying COVID-19 symptoms, and that even in mild cases of the disease, symptoms can last for a very long time. 

First Pharmacogenomics Study on COVID-19 Vaccine Reactions

In January 2022, Helix scientists published the first pharmacogenomics study on COVID-19 vaccine reactions, reflecting the power of collecting and combining phenotypic data with comprehensive sequencing on large populations. 

Scientists surveyed more than 17,000 participants from the Helix DNA Discovery Project and Healthy Nevada Project, who had their DNA previously sequenced with the Helix Exome+ assay, and asked respondents about their specific reactions to the COVID-19 vaccine, in order to perform a genome wide association study (GWAS). 

The study identified that participants with the HLA-A*03:01 allele who received the Pfizer vaccine are approximately twice as likely to have severe or extreme difficulties after receiving the vaccine (defined as reactions that would severely interfere with daily routine like fever and chills), than those without the allele. In contrast, the signal was very weak for those receiving the Moderna vaccine and did not approach genome-wide significance, despite a similar sample size. This held true across age groups, sex, and whether the person had a personal history of COVID-19 prior to the vaccination.

There is a lot more to be done to understand what causes the association, but one hypothesis may be that people with this HLA allele have a certain type of immune cells that have a stronger response to the Pfizer vaccine. 

This study shows that the closer we get to a state where a recipient’s genetic profile is readily available within a health system’s records, the closer we are to a standard where healthcare organizations can incorporate it into their patient care. 

The work continues 

While we don't entirely understand what makes one person more or less vulnerable than another for COVID-19, this research suggests that some people are slightly more at risk than others. This doesn't translate immediately into medical intervention, but these insights do tell researchers where to invest time and money to learn more and begin gathering evidence to justify clinical action. The insights we continue to gain about COVID-19 will be long-term investments in improving medical care. 

In addition to Helix’s COVID-19 research, their community health research collaborations with institutions like MUSC will help bring up new and interesting research questions that may have a direct impact on our ability to improve patient outcomes for a wide range of diseases ranging from heart disease to cancer. 

To learn more about how you can participate in MUSC’s community health research program, In Our DNA SC, and learn about your genetic risk for certain cancers and heart disease while also supporting a healthier South Carolina, please visit InOurDNASC.org.