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Iceland SARS-CoV-2 Screening Effort Finds Lower Infection Incidence in Children, Women

NEW YORK – Researchers in Iceland led by Decode Genetics' Kari Stefansson carried out a sequencing and population screening effort of people in the country at highest risk for SARS-CoV-2, and found that children under 10 years of age and women had a lower incidence of infection than adolescents or adults and men.

As the researchers wrote in their study on Tuesday in the New England Journal of Medicine, COVID-19 was first diagnosed in Iceland at the end of February, but the data are limited on how SARS-CoV-2, the virus that causes the disease, enters and spreads in a population. In order to elucidate its spread in Iceland, Stefansson and his colleagues tested 9,199 people living in the country who were symptomatic, had recently traveled to high-risk countries, or had contact with infected persons, as they were the ones at highest risk. They sequenced SARS-CoV-2 from 643 samples.

The researchers also carried out population screening in two ways. They issued an open invitation to 10,797 people, and they also sent random invitations to 2,283 people to come in for testing.

The researchers found that a total of 1,221 (13.3 percent) of the people who were recruited for the targeted approach tested positive for SARS-CoV-2. Of those tested in the general population, 87 (0.8 percent) in the open-invitation screening and 13 (0.6 percent) in the random-population screening tested positive for the virus. In total, 6 percent of the population was screened.

"Children under 10 years of age were less likely to receive a positive result than were persons 10 years of age or older, with percentages of 6.7 percent and 13.7 percent, respectively, for targeted testing; in the population screening, no child under 10 years of age had a positive result, as compared with 0.8 percent of those 10 years of age or older," the authors wrote. "Fewer females than males received positive results both in targeted testing (11 percent vs. 16.7 percent) and in population screening (0.6 percent vs. 0.9 percent)."

They also noted that the haplotypes of the sequenced SARS-CoV-2 viruses were diverse and changed over time, but that the percentage of infected participants that was determined through population screening remained stable for the 20-day duration of screening, which was consistent with the beneficial effect of containment efforts.

In the early targeted testing, 65 percent of the participants who tested positive for SARS-CoV-2 had recently traveled outside Iceland. In the later phase, 15.5 percent had recently traveled outside the country, the researchers found. Similarly, they noted that the proportion of participants in the population screening and who had recently traveled outside the country also fell rapidly during the study period.

Of the participants who tested positive from the early targeted-testing phase and who had traveled, 86.1 percent had visited areas designated as being at high risk by the end of February, such as China and the Alps mountain regions in Austria, Italy, and Switzerland. However, the researchers also found that 12 of 87 participants with positive tests in the screening group had recently traveled to the UK, which suggested relatively early spread of the virus in that country's population.

In sequencing SARS-CoV-2 RNA extracted from 643 samples, the researchers obtained coverage of more than 90 percent of the virus' genome from 581 samples and more than 67 percent from 605 samples. They called 409 sequence variants, 291 of which were not found in the GISAID database. To shed further light on the geographic origin of the SARS-CoV-2 infections in residents of Iceland, they generated a median-joining network of 1,547 complete viral sequences — 513 from complete viral genomes from Icelanders and 1,034 from other populations around the world.

Of the 157 sequenced virions the researchers obtained during the early targeted testing, they found that 143 were in the A2 clade. While the A and B haplotypes are common in East Asia, the B1a haplotype is at the center of the outbreak on the West Coast of the US, and A2a and its descendants are almost exclusively found in European populations.

The composition of haplotypes changed substantially from early targeted testing to later targeted testing, however, as the A2a1 and A2a2 haplotypes that had collectively made up 103 of 157 haplotypes in the early-targeted testing were reduced to 115 of 361 haplotypes in the later-targeted testing. The A1a and other A2a-derived haplotypes increased in frequency, most likely because the population screening had identified clusters of infected individuals who seeded infection from areas that had not been designated as high risk, such as the UK, the researchers said.

"The A2a3a and A2a2a haplotypes were the two most common haplotypes in Iceland; of the 577 persons who provided samples that were sequenced, the A2a3a haplotype was found in 78 (13.5 percent) and the A2a2a haplotype was found in 45 (7.8 percent)," the authors wrote.

The researchers concluded that the frequency of SARS-CoV-2 infection in the overall Icelandic population was stable from March 13 to April 1, which appears to indicate that the containment measures the country had put in place are working.

"However," they added, "the virus has spread to the extent that unless we continue to test and isolate, track contacts, and quarantine, we are likely to fail in our efforts to contain the virus."