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. 2020 Jun 11;382(24):2302-2315.
doi: 10.1056/NEJMoa2006100. Epub 2020 Apr 14.

Spread of SARS-CoV-2 in the Icelandic Population

Daniel F Gudbjartsson  1 , Agnar Helgason  1 , Hakon Jonsson  1 , Olafur T Magnusson  1 , Pall Melsted  1 , Gudmundur L Norddahl  1 , Jona Saemundsdottir  1 , Asgeir Sigurdsson  1 , Patrick Sulem  1 , Arna B Agustsdottir  1 , Berglind Eiriksdottir  1 , Run Fridriksdottir  1 , Elisabet E Gardarsdottir  1 , Gudmundur Georgsson  1 , Olafia S Gretarsdottir  1 , Kjartan R Gudmundsson  1 , Thora R Gunnarsdottir  1 , Arnaldur Gylfason  1 , Hilma Holm  1 , Brynjar O Jensson  1 , Aslaug Jonasdottir  1 , Frosti Jonsson  1 , Kamilla S Josefsdottir  1 , Thordur Kristjansson  1 , Droplaug N Magnusdottir  1 , Louise le Roux  1 , Gudrun Sigmundsdottir  1 , Gardar Sveinbjornsson  1 , Kristin E Sveinsdottir  1 , Maney Sveinsdottir  1 , Emil A Thorarensen  1 , Bjarni Thorbjornsson  1 , Arthur Löve  1 , Gisli Masson  1 , Ingileif Jonsdottir  1 , Alma D Möller  1 , Thorolfur Gudnason  1 , Karl G Kristinsson  1 , Unnur Thorsteinsdottir  1 , Kari Stefansson  1
Affiliations

Spread of SARS-CoV-2 in the Icelandic Population

Daniel F Gudbjartsson et al. N Engl J Med. .

Abstract

Background: During the current worldwide pandemic, coronavirus disease 2019 (Covid-19) was first diagnosed in Iceland at the end of February. However, data are limited on how SARS-CoV-2, the virus that causes Covid-19, enters and spreads in a population.

Methods: We targeted testing to persons living in Iceland who were at high risk for infection (mainly those who were symptomatic, had recently traveled to high-risk countries, or had contact with infected persons). We also carried out population screening using two strategies: issuing an open invitation to 10,797 persons and sending random invitations to 2283 persons. We sequenced SARS-CoV-2 from 643 samples.

Results: As of April 4, a total of 1221 of 9199 persons (13.3%) who were recruited for targeted testing had positive results for infection with SARS-CoV-2. Of those tested in the general population, 87 (0.8%) in the open-invitation screening and 13 (0.6%) in the random-population screening tested positive for the virus. In total, 6% of the population was screened. Most persons in the targeted-testing group who received positive tests early in the study had recently traveled internationally, in contrast to those who tested positive later in the study. 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% and 13.7%, respectively, for targeted testing; in the population screening, no child under 10 years of age had a positive result, as compared with 0.8% of those 10 years of age or older. Fewer females than males received positive results both in targeted testing (11.0% vs. 16.7%) and in population screening (0.6% vs. 0.9%). The haplotypes of the sequenced SARS-CoV-2 viruses were diverse and changed over time. The percentage of infected participants that was determined through population screening remained stable for the 20-day duration of screening.

Conclusions: In a population-based study in Iceland, children under 10 years of age and females had a lower incidence of SARS-CoV-2 infection than adolescents or adults and males. The proportion of infected persons identified through population screening did not change substantially during the screening period, which was consistent with a beneficial effect of containment efforts. (Funded by deCODE Genetics-Amgen.).

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Figures

Figure 1
Figure 1. Study Design for Targeted Testing and Population Screening.
In Iceland, targeted testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) began on January 31, 2020, and involved persons who were deemed to be at high risk for infection (i.e., those who were symptomatic, had traveled to high-risk countries, or had contact with infected persons). In the population screening, data from the open-invitation subgroup and random-sample subgroup were evaluated separately.
Figure 2
Figure 2. Distribution of Targeted Testing and Population Screening for SARS-CoV-2 and Percentages of Positive Results, According to Age and Sex.
Shown is the distribution according to age and sex among all the participants in the study who were targeted for testing for the presence of SARS-CoV-2 (Panel A), among those who participated in the open invitation of the population screening (Panel B), and among those who participated in the random sample (Panel C). Also shown are the percentages of participants who tested positive stratified according to sex in the targeted-testing group (Panel D) and in the population-screening group (Panel E). In addition, the percentage of participants who tested positive in the population screening is shown according to sampling date in the open invitation (black) and the random sampling (red) (Panel F). The solid blue curve in Panel F indicates the logistic-regression line, and the dashed lines indicate the 95% confidence intervals (CI) of the logistic regression. The logistic-regression slope corresponds to a change of −2% (95% CI, −5 to 1) in the infection rate per day. The vertical bars indicate 95% confidence intervals for age groups (in Panels D and E) and for individual dates (in Panel F).
Figure 3
Figure 3. Distribution of Variants across the SARS-CoV-2 Genome, a Median-Joining Network of Haplotypes, and Cumulative Counts from Targeted Testing and Population Screening.
Panel A shows the distribution of variants across the SARS-CoV-2 genome. The genes of SARS-CoV-2 are E (envelope small membrane protein), M (membrane protein), N (nucleoprotein), S (spike protein), and ORFs (open reading frames) 10, 1ab, 3a, 6, 7a, 7b, and 8. The different subsets that were considered included all variants, variants only observed in Iceland, and variants that were determined by the variant effect predictor to have a low effect (synonymous variants), a moderate effect (missense variants), or a high effect (loss-of-function variants). Panel B shows a median-joining network of 802 haplotypes from 1547 SARS-CoV-2 sequences (of which 513 are from Iceland). Each circle represents a different sequence type, in which the size of the circle reflects the number of carrier hosts, and the lines between circles represent one or more mutations that differentiate the sequence types. Circles are colored according to the regions where samples were obtained. The principal clades are outlined and labeled, with the number of sequences from Icelanders shown in parentheses. Haplotypes from clade A are not outlined. Panel C shows the cumulative counts of SARS-CoV-2 haplotypes from targeted testing and population screening as a function of sampling date. A2a* refers to all A2a haplotypes except A2a1, A2a2, and A2a3. The dashed vertical line indicates the start of the population screening.
Figure 4
Figure 4. Overall Clusters in the Contact-Tracing Network, a Network Cluster Including a Novel Domestic Mutation, and Source of Exposure.
Panel A shows an overview of all clusters in the contact-tracing network with SARS-CoV-2 haplotypes. Panel B shows a contact-tracing network for a cluster that included a novel domestic mutation (24054C→T). Person T25 carried both the A2a1a strain and the A2a1a+25958 strain. Contact-tracing networks show infected persons as nodes and a connection between two nodes where a transmission of infection or contact has been established. In cases in which the direction of transmission was ambiguous, a bidirectional arrow is shown. Persons who traveled internationally are indicated in boxes representing their travel destination. The colors of nodes represent the haplotype of the viral strain, either as a clade or a clade plus one or more mutations. Additional mutations are represented by a position number beside each node. The labels on the nodes are identifiers given in increasing order of identification (e.g., T6 is the sixth case reported). Red X marks indicate recorded contacts that are inconsistent with the viral haplotypes carried by each person. Panel C shows the type of exposure from contact-tracing data according to the date of isolation and percentage (top graph) and total number (bottom graph). The type of exposure is classified for each positive case into the following categories: family, unknown, social, work (including schools), tourism (reported working domestically in tourism), and travel (international travel).
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