key: cord-1035061-fmlm4bgk
authors: Kant, Ravi; Nguyen, Phuoc Truong; Blomqvist, Soile; Erdin, Mert; Alburkat, Hussein; Suvanto, Maija; Zakham, Fathiah; Salminen, Veera; Olander, Viktor; Paloniemi, Minna; Huhti, Leena; Lehtinen, Sara; Luukinen, Bruno; Jarva, Hanna; Kallio-Kokko, Hannimari; Kurkela, Satu; Lappalainen, Maija; Liimatainen, Hanna; Hannula, Sari; Halkilahti, Jani; Ikonen, Jonna; Ikonen, Niina; Helve, Otto; Gunell, Marianne; Vuorinen, Tytti; Plyusnin, Ilya; Lindh, Erika; Ellonen, Pekka; Sironen, Tarja; Savolainen-Kopra, Carita; Smura, Teemu; Vapalahti, Olli
title: Incidence Trends for SARS-CoV-2 Alpha and Beta Variants, Finland, Spring 2021
date: 2021-12-03
journal: Emerg Infect Dis
DOI: 10.3201/eid2712.211631
sha: aaa711bf99fa539863e69b2be79fc6c4523e9ecb
doc_id: 1035061
cord_uid: fmlm4bgk

Severe acute respiratory syndrome coronavirus 2 Alpha and Beta variants became dominant in Finland in spring 2021 but had diminished by summer. We used phylogenetic clustering to identify sources of spreading. We found that outbreaks were mostly seeded by a few introductions, highlighting the importance of surveillance and prevention policies.

To assess the temporal epidemiologic dynamics among different variants of concern and identify spreading events and sources of SARS-CoV-2 cases detected in Finland, we began sequencing 400-1,000 virus samples per week collected during December 2020-May 2021 and analyzed the resulting genomes (n = 14,080), which are now available in the GISAID (https://www. gisaid.org) database. For quality control purposes, we removed all sequences with ≥2.0% gaps.

We analyzed the resulting dataset (n = 9,160) with Pangolin (https://cov-lineages.org) (8) to identify lineages, from which we fi ltered Alpha and Beta variants for phylogenetic analyses. Each phylogenetic tree was computed from the fi ltered sequences and a global reference dataset consisting of 5 representative sequences, 1 sequence from the country of origin (England for Alpha, South Africa for Beta) and 4 randomly chosen from other countries containing the same lineage, for each date during December 2020-May 2021. The reference datasets included 841 genomes for Alpha variant and 775 genomes for Beta variant trees. We aligned sequences using MAFFT (https://mafft.cbrc.jp) (9) and removed gaps in the resulting alignments by trimming 50 characters from both the 5′ and 3′ ends.

We then used the aligned sequences to compute the trees with a SARS-CoV-2-specifi c version of IQ-TREE 2 (10) using ModelFinder to identify and use the optimal nucleotide substitution model, Severe acute respiratory syndrome coronavirus 2 Alpha and Beta variants became dominant in Finland in spring 2021 but had diminished by summer. We used phylogenetic clustering to identify sources of spreading. We found that outbreaks were mostly seeded by a few introductions, highlighting the importance of surveillance and prevention policies.

performing 1,000 ultrafast bootstraps. We set the initial wild-type reference strain (GenBank accession no. NC_045512.2) as the outgroup. We assigned sequences to clusters using TreeCluster (11) based on an arbitrary branch length of 0.001 to identify major transmission chains. We collapsed clusters with ≤5 sequences for visualization purposes. By May 2021, there had been 93,393 laboratoryconfirmed SARS-CoV-2 infections reported in Finland (12); incidence peaks occurred in April and December 2020 and March 2021 (Appendix Figure 1 , panel A, https://wwwnc.cdc.gov/EID/article/27/12/21-1631-App1.pdf). During this period, the weekly number of cases was as high as 4,900. National vaccinations began in late December 2020, and within 7 months, 3.5 million (62.8% of total population) persons had received first doses and 1.4 million (24.5% of total population) second doses (13) . Seroprevalence remained low (<2%) until February 2021 (14) but increased because of growing vaccination coverage (Appendix Figure 1, panel B) .

Throughout 2020, sequencing-based surveillance of the virus was conducted in the Hospital District of Helsinki and Uusimaa (HUS; Helsinki, Finland), which had the highest number of COVID-19 cases in the country (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 variants led to increased sequencing and sampling efforts at points of entry into Finland (i.e., 3,669, 69.6%) had 132-663 sequences each. We detected 32 singletons (0.6% of Alpha detections) from Finland, suggesting that the epidemic was largely 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 cases). We included all available high-quality sequences from random populations from Finland and thus included data from both mild and severe cases. However, a proportion of the samples from the HUS region came from points of entry into Finland and other hospital districts. The proportions of these imported samples varied over the sampling period depending on travel restrictions and hospitalized case-patients, which may have led to nonrandomized sampling from the HUS region.

Beta variants formed 76 distinct clusters, of which 56 contained 910 sequences from Finland (9.9% of all sequences from Finland) ( Figure 2 ). We also identified 33 singletons, of which 23 were from Finland (2.2% of Beta detections). In total, there might have been 79 introductions from other countries, which seeded 1 major cluster (>100 Finland sequences) containing 167 sequences (15.9% of cases). Most Beta sequences were also from the HUS hospital district (n = 505, 48.1% of cases). Hospital district reports were based on data from the Finnish Institute for Health and Welfare (https://sampo.thl.fi), HUS, and Fimlab (https://fimlab.fi).

Altogether, our study shows both Alpha and Beta variants emerging early and rapidly beginning in December 2020. Most (98.2% Alpha, 86.8% Beta) formed clusters, and only a small proportion (0.6% Alpha, 2.2% Beta) were singletons. Because the singletons represent a small fraction of the sequences and many were transmitted directly from travelers, it is likely that a few introductions were able to seed the epidemic.

The Alpha and Beta variants dominated detected SARS-CoV-2 cases, although at lower numbers for Beta, during early 2021. Despite the rapid emergence of these variants, their incidence fell sharply (Appendix Figure 1, panel A) . Incidence in Finland has been low compared with other countries in Europe, permitting use of more moderately restrictive prevention measures. Incidence, and therefore seroprevalence, remained relatively low until vaccines became available. Practices and policies enacted in Finland, including frequent testing, contact tracing, isolation, quarantine, and other nonpharmaceutical interventions, helped effectively interrupt chains of transmission, and ongoing national efforts have resulted in most of the population of Finland receiving at least the first vaccine dose. These findings suggest that with proper surveillance and preventative measures, along with moderate restriction compliance, the spread SARS-CoV-2 could be mitigated effectively.

Investigation of SARS-CoV-2 variants of concern

Detection of a SARS-CoV-2 variant of concern in South Africa

Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus

Increased transmissibility and global spread of SARS-CoV-2 variants of concern as at

Kinetics of neutralizing antibodies of COVID-19 patients tested using clinical D614G, B.1.1.7, and B 1.351 isolates in microneutralization assays

COVID-19 mRNA vaccine induced antibody responses against three SARS-CoV-2 variants

Increased mortality in community-tested cases of SARS-CoV-2 lineage B.1.1.7

Assignment of epidemiological lineages in an emerging pandemic using the Pangolin tool

MAFFT multiple sequence alignment software version 7: improvements in performance and usability

IQ-TREE 2: new models and effi cient methods for phylogenetic inference in the genomic era

TreeCluster: clustering biological sequences using phylogenetic trees

COVID-19 cases in the infectious diseases registry

COVID-19 vaccinations in Finland: vaccinations over time in hospital care districts per age group

Report of the population serology survey of the coronavirus epidemic

European Centre for Disease Prevention and Control. SARS-CoV-2 variants of concern as of 15

Unidentifi ed cyst-forming sporozoon causing encephalomyelitis and myositis in dogs

Review of Neospora caninum and neosporosis in animals

Detection of immunoglobulin G antibodies to Neospora caninum in humans: high seropositivity rates in patients who are infected by human immunodefi ciency virus or have neurological disorders

We acknowledge CSC-IT Center for Science, Finland, for providing computational resources.This study was supported by the Academy of Finland (grant number 336490), VEO European Union's Horizon 2020 (grant number 874735), Finnish Institute for Health and Welfare, Jane and Aatos Erkko Foundation, and Helsinki University Hospital Funds (TYH2018322 and TYH2021343).

From the neo-(Latin, "new") + spora (Greek, "seed") and canis (Latin, "dog"), Neospora caninum is a sporozoan parasite that was fi rst described in 1984. It is a major pathogen of cattle and dogs but can also infect horses, goats, sheep, and deer. Antibodies to N. caninum have been found in humans, predominantly in those with HIV infection, although the role of this parasite in causing or exacerbating illness is unclear.