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Explore, Verify, Predict: Genetic Analysis of SARS-CoV-2 Variants Responsible for COVID-19 Cases in Hungary

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Genetics research, aiming to identify SARS-CoV-2 variants responsible for pandemic COVID-19 cases, is a valuable tool to explore the geographical spread of the virus retrospectively, as well as to predict the presumable long-term effectiveness of vaccine candidates under development. A consortial research program involving four academical cities of Hungary (Szeged, Pécs, Debrecen, Budapest) represents a significant step forward, and will be integrated into the international collaboration of COVID research. The genome-wide analysis of SARS-CoV-2 identified from patient samples is a unique source of information, independent of other epidemiological data and studies. It is a specific method appropriate to trace back and characterize (model) the spring/summer wave of the pandemics, and reveals the specific virus variants currently spreading in the region of Hungary.

The Hungarian research project, focusing on the genetic analysis of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) identified from clinical samples, is led by the ELKH Biological Research Centre (BRC). It is executed in co-operation with the Virology National Laboratory of Hungary (belonging to the University of Pécs) and participating national clinical laboratories for diagnostics. The most recent findings from the project support the theory that in Hungary the current (autumn) wave of the COVID-19 pandemic is independent of the first outbreak of the virus witnessed by the population of the country in spring. This means that the current epidemiological situation is not a consequence of a continuous evolution of transmission originating from latent spring cases. Instead, it results from a new introduction at midsummer. In addition, a comparative analysis of the identified virus variants verifies that the first rise of COVID-19 cases in spring remained localized in the affected regions of the country, supporting the effectiveness of protective safety measures in terms of preventing or at least slowing the spread of viral transmission. In contrast, genome sequencing (i.e. the precise genetic analysis of the genes defining SARS-CoV-2) of samples from the current (second) wave has revealed a country-wide chain of infection, supporting the role of significant internal transmission.

“Significantly, the genetic material of SARS-CoV-2 is constantly changing, but this process is relatively slow compared to the same microbiological feature of other viruses (e.g. influenza)”, said Professor Dr. Ferenc Jakab, head of the Virology National Laboratory (VNL) of Hungary and Dr. Gábor Kemenesi, researcher at the VNL. However, the natural modifications (mutations) of the viral genome can play a significant role in the viability and contagiousness of the virus. The temporal and spatial maps of these patterns of gene mutations reveal important information on the lines of transmission.

“The evolutionary tree developed on the basis of the identified genetic variants of SARS-CoV-2 indicates that in Hungary the first few cases of infection occurred at the end of February and in the first half of March, i.e. simultaneously with the COVID-19 outbreak in Western Europe. These data disprove the common belief that the virus may have appeared earlier in Hungary,” said the researchers Dr. Eszter Ari and Dr. Bálint Márk Vásárhelyi, who executed the bioinformatics analyses of the identified genome sequences.

As the research project has revealed, the SARS-CoV-2 variants responsible for the current chains of infection in Hungary are the same as those spreading in Europe. Specifically, the variants dominating the Hungarian lines of transmission are those that developed in other European countries during springtime. “Building on the prominent knowledge of our research groups in evolutionary biology and bioinformatics, we execute fast and real-time genomic analyses of clinical SARS-CoV-2 samples, aiming to characterize the domestic spread of the virus, as well as to immediately identify novel virus variants,” said the project leaders, Dr. Bálint Kintses and Dr. Balázs Papp, members of BRC and the Hungarian Centre of Excellence for Molecular Medicine (HCEMM). National data on SARS-CoV-2 variants appearing in countrywide clinical practice make an important contribution to international COVID monitoring. Ongoing improvement of our knowledge on the pandemic is essential to prepare for future challenges, including a vigilant detection of any novel variants. Monitoring SARS-CoV-2 variants is also a valuable tool to assess the presumable effectiveness of future vaccination programmes, as well as that of the available therapeutic options.

A detailed description of the research project, and the analysis and interpretation of genome sequencing data, including a summary of SARS-CoV-2 variants currently spreading in Hungary are available here (in Hungarian).

Brief statistics

The number of verified SARS-CoV-2-positive cases has been increasing exponentially since the first cases were diagnosed in December 2019. Globally, as of 8 December 2020, there have been 66,729,375 confirmed cases of COVID-19, including 1,535,982 deaths, as reported by the WHO. To put it in perspective, seasonal influenza-associated respiratory disease is estimated to cause up to 650,000 deaths per year worldwide, while the most recent pandemic caused by influenza A (H1N1) virus, occurring in 2009, is estimated to have caused between 100 000 and 400 000 deaths globally in the first year. Currently, the number of confirmed COVID-19 cases is over 250,000 in Hungary, and over 6,000 Covid-related deaths have occurred so far (population: 9.77 million).