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deCODE Study in NEJM Sheds Light on SARS-CoV-2 Genetics and True Prevalence in Iceland

Public health authorities around the world could gain critical new insight into COVID-19 through a study that offers one of the most in-depth looks to date at SARS-CoV-2 infection rates in both high-risk populations and the general public.


How common is it for people to be infected with the SARS-CoV-2 virus but have no symptoms at all or only mild cold-like symptoms? How does the virus spread once it enters a region, and how quickly does it acquire new mutations?

A new study from deCODE Genetics, a subsidiary of Amgen, is providing the world with hard data that will help to answer these questions. Conducted in collaboration with Iceland’s health authorities, the study is one of few published so far to test both high-risk individuals and people with no known risk factors to assess the true prevalence of SARS-CoV-2 infections.

To go deeper, deCODE also sequenced viral samples taken from 643 individuals to identify distinct strains of the virus and learn how it arrived in Iceland and spread and mutated after its arrival. The results, published in the New England Journal of Medicine (NEJM) on April 14, underscore the effectiveness and necessity of aggressive testing, isolation of cases, and physical distancing, as well as the urgency of more testing to contain the virus and prevent disease.

“Our civic duty”

In the worldwide battle against COVD-19, health authorities have generally focused their testing resources on people with symptoms of infection, such as fever, dry cough, and difficulty breathing. But to really understand the virus—how lethal it is and how many of those infected get serious illness—it’s important to gauge the true prevalence of infection in the general population.

As the pandemic reached Iceland, Kári Stefánsson, the CEO and founder of deCODE, saw an opportunity to apply deCODE’s scientific expertise to this challenge. “We are a very small country with a population of 360,000,” he observed. “There are not a lot of resources in the country to do work like this. But deCODE has the resources, so we have looked at this as our civic duty to do this testing.”

“When Kári conceived this idea in early March, we assured him that we would provide the resources and support necessary to move quickly,” said Dave Reese, executive vice president, R&D. “Stopping the spread of COVID-19 is the biggest challenge the world has faced in decades, so there’s no better use right now for deCODE’s world-class analytic and sequencing capabilities.”

In partnership with Iceland’s health care authorities, deCODE quickly repurposed its scientific talent and resources to do up to a thousand or more SARS-CoV-2 tests daily. While the National University Hospital of Iceland (NUHI) continued to test individuals with symptoms, a history of travel to high-risk areas, or contact with infected individuals, deCODE issued an open invitation to the general public to volunteer for screening. Starting on April 1, deCODE augmented its open screening program by inviting randomly selected Icelanders between age 20 and 70 to be screened.

“We have substantial experience in dealing with population data, and that turns out to be valuable when it comes to screening for a virus like COVID-19,” said Kári. “We have been working 24/7 to screen for and sequence the virus.”

Detecting hidden infections

Results from the NEJM study showed that, as of April 4, 13.3% of the 9,199 high-risk individuals screened by NUHI tested positive for the virus. Women were less likely than men to test positive (11% versus 16.7%), and children under 10 were at also lower risk for infection (6.7%).

Of the 10,797 volunteers tested by deCODE in the open invitation screening, 87 individuals (0.8%) tested positive. In random screening conducted from April 1 to April 4, 13 of 2,283 people screened (0.6%) tested positive. In the combined open invitation and random screening efforts, 43 of the 100 positive test results were in individuals who reported no symptoms at the time they were tested, and the remaining positive tests were in people with mild cold-like symptoms, such as cough and runny nose.

deCODE’s sequencing of the virus showed that there were a variety of haplotypes, or strains of SARS-CoV-2, present in Iceland. The first wave of infections to hit the country was linked primarily to strains that came in with travelers returning from Italy and Austria.

In the smaller number of infections detected through deCODE’s screening, strains derived from travel to the UK and the US were more common – countries that had not yet been designated high-risk areas when the Icelanders who tested positive were travelling there. The finding provides fresh evidence that the virus can be present in populations weeks before large numbers of people start to show symptoms.

Over time, the number of travel-related infections in Iceland declined significantly, as did the number of infections linked to social activity, highlighting the effectiveness of social distancing and Iceland’s ban on large gatherings. Since late March, most of the new cases in the country have come through exposure to infected family members or unknown sources.

deCODE also identified 409 sequence variants, or mutations, in the virus samples it tested. That included 291 new mutations that are not reported in the GISAID database (Global Initiative on Sharing All Influenza Data).

More screening planned and needed

The screening done by deCODE will have immediate and practical public health benefits, as apparently healthy individuals who are nonetheless infected are informed and isolated to reduce further spread of the virus. On a per capita basis, Iceland has mounted the most extensive SARS-CoV-2 testing effort of any nation, and the study results underscore the need for continued testing, Kári said.

“We have screened more than anyone else, and that has been done to find the cases that are looming in society that are not being caught by the health care system,” said Kári. “We have had aggressive tracking of those infected, and we have been very aggressive in putting people into quarantines. And that has worked.”

“To bend the curve of this pandemic as quickly as possible, we need scientifically accurate information on how COVID-19 spreads in communities,” said Robert A. Bradway, chairman and chief executive officer at Amgen. “I believe deCODE’s swift response to this emergency and the insights they have generated will give the rest of the world a stronger scientific foundation for public health decisions.”

The Icelandic health authorities and deCODE are continuing their respective testing programs for high-risk individuals and members of the general public, with new data posted daily on https://www.covid.is/data. deCODE has also received permission from Iceland’s health authorities to add the COVID-19 data to its comprehensive database of genetic and health information on Iceland’s population. Combining these data sets could lead to fresh insights on genetic and health-related factors that might influence the risk for infection and the severity of illness among those infected.



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