Study elucidates importation risks and disproportionate spread of SARS-CoV-2 variants of concern in the Netherlands

In a recent study posted to the medRxiv* pre-print server, researchers used whole-genome sequencing (WGS) to explore the transmission dynamics of four severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) – Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2) in the Netherlands.

Background

In 2021, all the four VOCs were globally circulating, and they resurged coronavirus disease 2019 (COVID-19) outbreaks, impeding efforts to control the pandemic worldwide. Of these, the Alpha and Delta VOCs primarily dominated in the Netherlands. Hence, the Dutch government restricted flights from countries where Alpha and Delta had first emerged, simultaneously implementing several non-pharmaceutical interventions (NPIs) to mitigate their effect between 2020 and 2021.

More importantly, the government started a nationwide surveillance program and scaled up its WGS efforts for monitoring the introduction and spread of novel SARS-CoV-2 variants.

About the study

In the present study, spanning 48 weeks between September 2020 and August 2021, researchers sequenced randomly collected 39,844 high-quality SARS-CoV-2 whole genomes from the 1,792,759 laboratory-confirmed SARS-CoV-2-positive samples to characterize the importation risks and spread of Alpha, Beta, Gamma, and Delta VOCs in the Netherlands.

They used the NextClade lineage assignment to genotype the SARS-CoV-2-positive samples.

For a deeper insight into the overseas introduction of SARS-CoV-2 VOCs, the researchers subsampled a representative set of Dutch and overseas sequences collected within the same time frame. They reconstructed time-scaled, maximum likelihood (ML) phylogenies and used a Bayesian approach to perform distinct trait analyses on these fixed phylogeny trees.

They used a different set of Alpha and Delta WGS data for continuous phylogeographic analyses to estimate events of oversees introductions from other countries into the Netherlands for all the four VOCs to reconstruct the origin of ancestral strains.

Lastly, the research team fitted the weekly data of sampled VOCs to a logistic growth model for quantifying the growth rates of the Alpha and Delta VOCs in the Netherlands.

Study findings

The WGS genotyped most samples gathered during the starting phase of the study to clade 20A and its sublineages, 20B and 20E. The introduction of NPIs, such as closing nightlife establishments and restaurants in October 2020, reduced cases from these lineages circulating till December 2020 in the Netherlands.

The Netherlands imposed a nationwide lockdown after the first Alpha case, reported on December 5, 2020. Although the lockdown slightly decreased Alpha cases, it still became the dominant circulating SARS-CoV-2 VOC by February 2021, i.e., week 6 of the study period. Later, the Beta and Gamma VOCs were also identified via WGS efforts but did not outcompete Alpha.

When Alpha cases began to decline by the end of April 2021, the Dutch government began relaxing lockdown restrictions. Around the same time, WGS identified the first Delta case in the Netherlands, and by June 2021, the Delta VOC accounted for 24% of all sequenced genomes.

In June 2021, SARS-CoV-2 prevalence was lowest in the Netherlands, with only 8,690 SARS-CoV-2-positive cases. However, within a week of reopening, COVID-19 cases surged over 50,000 in weeks 26 and 27 (July 2021), and most were due to Delta. In just three weeks, Delta replaced Alpha as the dominant SARS-CoV-2 VOC in the Netherlands, with over 90% of surveilled genomes assigned to the Delta variant by mid-July 2021.  Additionally, the Delta cases rapidly surged inter-regionally in late June 2021, as indicated by a more than 400% estimated increase in total phylogenetic branch movements by July 2021. 

The study estimated that the most overseas introduction events for the ancestral strains were from Europe, and the Alpha, Beta, Gamma, and Delta VOCs accounted for 71%, 29%, 71%, 79% of these events, respectively. Notably, these European introductions continued to occur during the travel ban period in the Netherlands, suggesting the need for pan-European flight restrictions.

The researchers identified that the large, densely populated cities in the North Brabant, Utrecht, North and South Holland, also international and regional travel hubs of the Netherlands, formed the first (local) core cluster of dominant source locations in March 2020.

The Alpha and Delta VOCs were first detected in these locations and circulated mostly within these areas during the first four weeks after the introduction and dispersal to other regions was relatively less frequent. Later, bidirectional and asymmetric exchanges in phylogenetic branches between different regions emerged throughout the country amid strict lockdown.

Furthermore, the researchers observed that the Delta VOC showed a weekly growth rate of 103%, about two times higher than Alpha, which showed a weekly growth rate of 45%. Interestingly, Alpha and Delta replaced their predecessors rapidly with similar rates across most age groups.

Conclusions

The study highlighted that all the VOC lineages detected in the Netherlands before September 2020 until August 2021 originated mainly from its European neighbors. The very first introduction of SARS-CoV-2 in the Netherlands in February 2020 was due to travelers from Northern Italy, the seeding place of the earliest European SARS-CoV-2 transmission. Moreover, even after implementing international travel restrictions, the Netherlands remained highly vulnerable to importation risks of novel SARS-CoV-2 variants due to the European Union border policies.

The study findings highlight the need for continued surveillance of the cluster of locations where the VOCs were first detected to gather actionable information early on about the introduction of novel SARS-CoV-2 variants and timely containment of infections and onward transmission.

*Important notice

 medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Written by

Neha Mathur

Neha is a digital marketing professional based in Gurugram, India. She has a Master’s degree from the University of Rajasthan with a specialization in Biotechnology in 2008. She has experience in pre-clinical research as part of her research project in The Department of Toxicology at the prestigious Central Drug Research Institute (CDRI), Lucknow, India. She also holds a certification in C++ programming.