Regional importation and asymmetric within-country spread of SARS-CoV-2 variants of concern in the Netherlands

Abstract

Variants of concern (VOCs) of SARS-CoV-2 have caused resurging waves of infections worldwide. In the Netherlands, Alpha, Beta, Gamma and Delta variants circulated widely between September 2020 and August 2021. To understand how various control measures had impacted the spread of these VOCs, we analyzed 39,844 SARS-CoV-2 genomes collected under the Dutch national surveillance program. We found that all four VOCs were introduced before targeted flight restrictions were imposed on countries where the VOCs first emerged. Importantly, foreign introductions, predominantly from other European countries, continued during these restrictions. Our findings show that flight restrictions had limited effectiveness in deterring VOC introductions due to the strength of regional land travel importation risks. We also found that the Alpha and Delta variants largely circulated more populous regions with international connections after their respective introduction before asymmetric bidirectional transmissions occurred with the rest of the country and the variant dominated infections in the Netherlands. As countries consider scaling down SARS-CoV-2 surveillance efforts in the post-crisis phase of the pandemic, our results highlight that robust surveillance in regions of early spread is important for providing timely information for variant detection and outbreak control.

Figure 1:. SARS-CoV-2 infections and genotypes circulating in the Netherlands from September 2020 to August 2021.

(A) Weekly number of laboratory-confirmed SARS-CoV-2 cases (1st panel from the top) and sequenced genomes (2nd panel). Genotype proportions of sequences (3rd panel) are shown as stacked bars colored by NextClade designations as in (C). Breakdown of positive cases by age group from data provided by the Dutch National Institute for Public Health and Environment (4th panel). Aggregated weekly average percentage change in mobility to the baseline in the Netherlands from Google’s COVID-19 community mobility reports. Baseline mobility is the median value from a 5-week period between 3 January 2020 and 6 February 2020, prior to the COVID-19 pandemic in Europe (5th panel). (B) Mean number of laboratory-confirmed cases per 100,000 inhabitants (data from the Dutch National Institute for Public Health and Environment) and total number of sequenced genomes in different Municipal and Regional Health Service (GGD) regions over the entire study period. (C) Maximum clade credibility tree of sequences based on a downsampled set of 2,246 sequences that is representative of the weekly relative proportions of reported case numbers across different GGD regions. Tips are colored by NextClade genotype designations.

Figure 2:. Likely overseas introduction of VOC lineages into the Netherlands at the continental level.

For each VOC lineage, a time-scaled maximum likelihood phylogeny using the Dutch and their nearest overseas neighboring sequences was inferred. Discrete trait analyses were performed to infer the likely continental region of ancestral states. Subtrees or singletons with ancestral nodes attributed to an overseas origin but subtend only Dutch sequences are drawn. Shaded plot area denotes the timespan when a targeted flight restriction was imposed on the country where the VOC lineage first emerged (i.e. (A) Alpha, United Kingdom.; (B) Beta, South Africa; (C) Gamma, Brazil; (D) Delta, India)

Figure 3:. Spatiotemporal spread of the Alpha and Delta variants of concern in the Netherlands.

Reconstruction of continuous phylogeography with nodes colored by time and the dispersal directionality of phylogeny branches with counterclockwise edges. (A, B) Alpha variant; (C, D) Delta variant. Top panels (A) and (C) show the reconstruction of specific labelled periods for each variant. Bottom panels (B) and (D) show the reconstruction for the entire study period.

Figure 4:. Estimated number of phylogenetic branch movements and growth rate estimations of Alpha and Delta variants in the Netherlands.

(A) Estimated number of phylogenetic branch movements between GGD regions over time as shown in Figure 3B and D. Solid line shows the number of branch movements from early dominant source regions including North and South Holland, Utrecht and Brabant. Dashed line shows number of branch movements from areas outside of these early dominant source locations. (B) Logistic growth regression of Alpha and Delta sequence proportions.