The rise and fall of Alpha and Beta variants of SARS-CoV2 in Finland in spring of 2021

Two SARS-CoV-2 Variants of Concern, Alpha (~ 80%) and Beta (~ 23%) rapidly became dominant in Finland in the spring of 2021 but diminished near summer. To assess their temporal epidemiological dynamics among Finnish cases, we began large-scale sequencing efforts to identify spreading events and sources via phylogenetic clustering analyses. The results show the majority belonged to clusters spreading in the community while few sequenced samples were singletons. The results highlight the importance of surveillance and preventative policies in controlling the epidemic.


Abstract
Two SARS-CoV-2 Variants of Concern, Alpha (~ 80%) and Beta (~ 23%) rapidly became dominant in Finland in the spring of 2021 but diminished near summer. To assess their temporal epidemiological dynamics among Finnish cases, we began large-scale sequencing efforts to identify spreading events and sources via phylogenetic clustering analyses. The results show the majority belonged to clusters spreading in the community while few sequenced samples were singletons. The results highlight the importance of surveillance and preventative policies in controlling the epidemic.

Main Text
Several new variants of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged globally, of which the most notable are the Variants of Concern (VOCs), which are Alpha (B.1.1.7) (1), Beta (B1.351) (2), Gamma (P.1) (3), and the most recent addition, Delta (B.1.617.2). Each is considered to pose an increased public health risk due having one or more of the following epidemiological characteristics: higher transmissibility (4), immune escape properties towards antibodies from previous infection (5), lower response towards current vaccines compared to the original wild type strains circulating in 2020 (6), and more severe outcomes or increased mortality rates (7). Detecting and monitoring these novel variants is essential in SARS-CoV-2 surveillance.
To assess the temporal epidemiological dynamics among different VOCs and identify spreading events and sources of SARS-CoV-2 cases detected in Finland, we began efforts to sequence ca. 500-1000 virus samples per week and analyzed resulting genomes (available in GISAID) collected between December 2020 and May 2021 (n = 14,080). These were quality controlled by removing all sequences with 2.0% or more gaps. The resulting data set (n = 9,160) was analyzed with pangolin (8) to identify lineages, from which Alpha and Beta variants were ltered for phylogenetic analyses. Each phylogenetic tree was computed from the ltered sequences and a global reference data set consisting of ve representative sequences (one from country of origin i.e, England for Alpha variant and South Africa for Beta variant, and four randomly chosen from other countries) of the same lineage for each date between December 2020 and May 2021. The reference datasets included 841 genomes for Alpha variant and 775 genomes for Beta variant tree. The sequences were aligned with MAFFT (9) and the resulting alignments were trimmed from both 5' and 3' ends by 50 characters to remove gaps. These were then used to compute the trees with a SARS-CoV-2 speci c version of IQ-TREE 2 (10) using ModelFinder (11) to utilize the most optimal nucleotide substitution model, and with 1,000 ultrafast bootstraps (12). Wuhan reference strain (NC_045512.2) was set as the outgroup. Sequences were assigned to clusters via TreeCluster (13) based on arbitrary branch length of 0.001 to identify major transmission chains. Clusters (≤ 5 genomes) were collapsed for visualisation purposes using ETE 3 (14), and the trees were visualized with ggtree (15) and ggtreeExtra (16) in R.

SARS-CoV-2 cases and vaccination rates in Finland
By May 2021, 93,393 laboratory con rmed SARS-CoV-2 infections have been reported in Finland (17). During this period, the weekly number of cases was up to ca. 4,900, and there have been three incidence peaks (April and December 2020, and March 2021) (Fig. 1A). National vaccinations began in late December 2020, and within seven months, 3.5 million rst (62.8% of total population), and 1.4 million (24.5% of total population) booster doses have been administered (18). The seroprevalence remained low (< 2%) until February 2021 (19), but has increased due to growing vaccination coverage (Fig. 1B).
Sequencing-based surveillance of the virus was conducted in the HUS throughout 2020, which had the highest COVID-19 cases in Finland (n = 21,742). Until December 18, 2020, only wild type strains of SARS-CoV-2 had been detected, but the emergence of Alpha and Beta led to increased sequencing and sampling efforts at the Finnish borders starting the week 51. Between December 2020 and May 2021, a total of 14,080 SARS-CoV-2 genomes representing ca. 20.4% of the PCR-con rmed SARS-CoV-2 infections (n = 65,921) have been sequenced.
During this time period, the incidence of Alpha (5,370 total detections, 58.6%) rapidly increased from 3 of

Phylogenetic analyses
The clustering analysis of Alpha variant (Fig. 3) shows 86 distinct clusters, of which 84 contained 5,270 sequences from Finland (57.5% of all Finnish sequences). The 13 largest clusters containing ≥ 100 Finnish sequences had between 132-663 sequences each (total n = 3,669, 69.6%). We detected 32 Finnish singletons (0.6% of Alpha detections), which suggests that the large part of the epidemic was seeded from a few introductions, which aligns with the super-spreading properties of SARS-CoV-2 epidemiology. Most Alpha sequences were from the HUS district (n = 3,476, 64,7% of all Alpha detections). The hospital districts reported are according to data from Finnish Institute for Health and Welfare (THL), HUS and Fimlab, and the sequences were from hospital districts and the border.
The Beta variants formed 76 distinct clusters, of which 56 contained 910 Finnish sequences (9.9% of all Finnish sequences) (Fig. 4). We also identi ed 33 singletons of which 23 were from Finland (2.2% of Beta detections). In total, there may have been 79 introductions from other countries, which seeded one major cluster (≥ 100 Finnish sequences) containing 167 sequences (15.9% of all Beta cases). Most Beta sequences were also from the HUS hospital district (n = 505, 48.1% of all Beta cases).

Conclusions
Altogether, our study shows Alpha and Beta variants emerging early and rapidly beginning in December 2020. The majority of both variants formed clusters (98.2% and 86.8%, respectively) and only a small proportion were singletons (0.6% and 2.2%, respectively). As the singletons represent a fraction of the sequences, and many were directly from travelers, it is likely that few introductions were able to seed the epidemic.
The Alpha variant dominated among detected SARS-CoV-2 cases along with Beta, although at lower numbers. Despite the rapid emergence of variants, their incidence has fallen sharply (Fig. 1A). This is concomitant with practices and policies enacted in Finland, which led to overall moderate restrictions and internationally modest COVID-19 incidence throughout the pandemic, and low immune pressure from  Phylogenetic tree of Finnish SARS-CoV-2 Alpha variant clusters and sequence distribution. We detected 86 clusters with ≥5 sequences (red circles), of which 84 contain 5,270 sequences sampled in Finland using TreeCluster, and 32 Finnish singletons (white circles). Each row in subsequent panels is equivalent to a cluster and shows the number of sequences from Finland and the proportion of sequences per Finnish region. The tree was constructed with the SARS-CoV-2 version of IQ-TREE2 with 1,000 ultrafast bootstraps.

Figure 4
Phylogenetic trees of Finnish SARS-CoV-2 Beta variant clusters and sequence distribution. We detected 76 clusters with ≥5 sequences (red circles), of which 48 contain 898 sequences sampled in Finland using TreeCluster, and 23 Finnish singletons (white circles) from 33. Each row in subsequent panels is equivalent to a cluster and shows the number of sequences from Finland and the proportion of sequences per Finnish region. The tree was constructed with the SARS-CoV-2 version of IQ-TREE2 with 1,000 ultrafast bootstraps.

Supplementary Files
This is a list of supplementary les associated with this preprint. Click to download.