Medically reviewed by Susan Kerrigan, MD and Marianne Madsen
Additions/comments provided by Surya Singh, MD
An island nation and several consumer genomics companies are joining the fight against the novel coronavirus 2019 (COVID-19) pandemic. They are joining forces with scientists across the world. All are trying to solve a riddle that emerged as cases of COVID-19 grew and has perplexed physician-scientists the world over.
In January of 2020, the virus was primarily causing serious infections and health complications in people over 65. According to the U.S. Centers for Disease Control and Prevention by mid-March of 2020, at least one quarter of the hospitalizations were for patients in their 50s or 40s. As the pandemic spread, even younger people began dying. Many had weakened immune systems. Others had preexisting conditions like asthma, diabetes, or hypertension. Yet expanded antibody testing has revealed many infected people who never got sick. Meanwhile, others who seemed young and healthy wound up on ventilators. Genetics may be responsible.
New Weapons
Governments might have been caught-flat footed by COVID-19; the genomics industry was well-prepared. As the virus spread, huge troves of data were enlisted in the fight. The best known DNA-testing company, 23andMe Inc., has been surveying customers to find the ones who have contracted the virus and its impact on their health. Yet the principal scientist at 23andMe admits that the company’s vast trove of data may be too limited, and ultimately insufficient for understanding the pandemic’s host genetics. Fortunately, the company is not alone.
Global collaboration drives the COVID-19 host genetics initiative. The effort enlists the human genetics community broadly, including academic centers (e.g., Columbia, Stanford, and the University of Utah), private companies (e.g., Helix Genomics), and governments – globally. With over 180 registered studies to date, the initiative will generate, share, and analyze data across all of them, and the number of registrants is still rising. By facilitating the discovery of the genetic determinants for COVID-19 susceptibility, severity, and outcomes, life-saving drugs could be better targeted and accelerated to communities and patients in need. People at high risk could be protected while low-risk people may be able to resume “normal lives.” The COVID-19 host genetics initiative has three goals: (1) fostering the sharing of resources; (2) analyzing studies to discover a genetic marker that indicates whether or not someone will catch the virus and, if so, how significant symptoms are likely to be; and (3) providing a platform for hosting research to benefit the scientific community.
Biobanks across Europe are contributing to this quest, including FinnGen, which has samples for some 5% of people in Finland. Protective or susceptibility DNA variants are being studied at Harvard University’s Personal Genome Project, which has recruited thousands of people who, along with sharing their full genome (their complete set of DNA), will be contributing updated information about their COVID-19 status. Iceland has also joined the fight.
Long a vacation destination for its icebergs and hot springs, Iceland is also a global leader in genomics and research. The government pointed out that the country has “…tested a higher proportion of inhabitants than any other country after deCode genetics started offering free screening among the general, non-symptomatic, non-quarantined population.” A global leader in genetics research, deCode has not only used data to protect the Icelandic population but to benefit the larger scientific community. With an homogeneous population of less than 400,000 people–many of whom can trace their families back to Viking settlements in the first millennia – it has been a goldmine for increasing our understanding of the relationship between genes and health. Now screening for the virus is showing scientists how COVID-19 differs in various locales and how it accomplishes its ongoing mutations. If underlying health issues were the sole factor, it would have similar mortality rates across the globe – which doesn’t seem to be true. Although most data is preliminary, it seems to behave differently amongst different populations.
Preparing for the Fight
The technology of genetic testing and genomic sequencing has come a long way in a quarter-century. In 2002, the zoonotic severe acute respiratory syndrome (SARS, caused by the virus SARS-CoV-1) was believed to have begun with a bat in the Guangdong province of southern China. As the CDC notes, human vulnerability to animal-borne viruses have increased “with unprecedented world population growth, greater interaction with wildlife, and the dramatic expansion of international air travel.”
Although still under scrutiny, the source of SARS-CoV-2 (the virus that causes COVID-19) may also be a bat handled in the so-called “wet” markets of Wuhan. After the original SARS (2002) outbreak, several studies examined how genetics may play a role in whether or not someone contracts the virus and how sick they become after an infection. One study discovered that among the study group, the genome CXCL10(-938AA) was always protective. It suggested identifying unique genetic components among those with immunity or those at high risk could reduce a virus’s impact.
Although most of the research for genetics and SARS-CoV-1 took place years after the epidemic, Chinese scientists sequenced the SARS-CoV-2 genome and posted it online less than two weeks after the first COVID-19 cases were reported. Studies are underway that look at everything from various genes to blood type (preliminary tests show higher risk among those with type A while type O has a lower risk.) While numerous studies have been done linking genes to various cancers, heart disease, and other conditions, far fewer have been done for common infectious diseases. In 2017, one study looked at the genetic link for numerous diseases from chickenpox to pneumonia. It examined questionnaires about infection history completed by 200,000 23andMe research participants of European ancestry. The study uncovered numerous genomes that were associated with immunity from the studied diseases.
In the ongoing evaluation of COVID-19 cases, it is clear there are other factors at play. It’s counterintuitive, but when the body fights too hard against infection your immune system can do more damage than the virus itself. This “cytokine storm” is one reason children do not seem to develop severe cases of COVID-19. Their immune systems aren’t well developed yet. According to deCode, women are also less vulnerable to infection. Your genes, of course, play a role in whether or not you get heart disease, diabetes, or many other chronic conditions. In the U.S., one factor with both genetic and lifestyle components stands out: weight. At New York University, doctors looked at over 4,000 patients and found that older patients who were 80 to 100 pounds overweight were far more likely to be hospitalized. Anecdotally, many younger, overweight patients across the county have become quite ill. Some who were described as having no underlying health conditions were above the CDC‘s recommended Body Mass Index.
Like green eyes and red hair, some of us may have relative immunity to COVID-19 encoded in our genes. Decoding this information could go a long way toward a vaccine or cure.
Written by John Bankston
References
- Severe outcomes among patients with Coronavirus Disease 2019 (COVID-19)
- Large scale testing of general population in Iceland underway
- The public health impact of COVID-19: why host genomics?
- Candidate genes associated with susceptibility for SARS-coronavirus
- Genome-wide association and HLA region fine-mapping studies identify susceptibility loci for multiple common infections