Researchers report a new SARS-CoV-2 variant of care in Uganda

The etiological causative agent of 2019 coronavirus disease (COVID-19) – severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – was first identified in Wuhan, China, in December 2019. Since then, the virus has infected more than 107. million people worldwide and caused more than 2.4 million deaths. Due to the high transmissibility, it was difficult to control the virus in an epidemic area.

Towards the end of 2020, a new variant of SARS-CoV-2 (line B.1.1.7) appeared in England and another, (B.1.351), also known as 501Y.V2, in South Africa. Both are observed to have increased transmissibility, with some early studies even suggesting an increase in virulence in these mutations.

In a worrying new development, an interdisciplinary research team from Uganda and the UK is reporting the emergence and spread of a new A-line SARS-CoV-2 variant with multiple protein changes throughout the viral genome. The researchers recently published their findings in a preprint on the medRxiv * server.

The researchers report the emerging A sublines, A.23 and A.23.1 of the SARS-COV-2.

The research team reports that the A.23.1 subline is the main virus line now observed in the Kampala region of Uganda. This subline reportedly encodes multiple spike proteins, nsp6 (nonstructural protein), ORF8 and ORF9 (open reading frames 8 and 9) protein changes. Some of these replacements are predicted to be functionally similar to those observed in line B variants of care (VOCs).

The Kampala region has become an epicenter of viral transmission in the country; Every day, 60-80% of the country’s new cases were identified there, from June 2020 to January 2021. The researchers generated the genomic sequence data from SARS-CoV-2 to track virus movements and changes in them.

The researchers also report that across the epidemic in the region, 39% of the strains can be classified as the major B line, while 61% are within the A line. Interestingly, when the transport was characterized by overland travel (mainly truck driver movements) and no flights, the line B.1 tribes prevailed. However, in the course of their investigation, the researchers unexpectedly found that until the end of January 2021, viruses of the A-line are almost exclusively found in the Kampala region.

Because the researchers identify the line A strain as coming from a truck driver (strain UG053) as basic to the newly emerging A.23 variant, they recommend continuous monitoring of all truck drivers entering and leaving Uganda. This will help to gain a better understanding of inland entry and exit through the country, and the circulation of the tribes in this region, where (large-scale) genomic surveillance is not yet exhaustive.

Notably, the genome sequences of 6 fatal Ugandan cases belonged to two lines A.25 and B.1.393. Although the SARS-CoV-2 line A is less common than line B in Europe, the UK and the US, the presence of line A viruses from fatal community cases across Uganda indicates that this line is circulating in the country and capable of is to severe infection.

To monitor the epidemic in more detail, the researchers generated the complete genome SARS-CoV-2 sequences from SARS-CoV-2 positive samples in Uganda. Based on this analysis, the researchers present a maximum likelihood phylogenetic tree by comparing all available complete and high-coverage references in Uganda.

Several variant lines were seen at low frequencies and only short and may seemingly extinct, similar to patterns seen in the UK and Scotland, the researchers write.

The researchers also found that the SARS-CoV-2 outbreaks in and around the prisons are the line A.23, with three amino acid (aa) changes encoded in the exposed S1 domain of the spike protein (F157L, V367F and Q613H ).

Whereas the sequence of the A.23.1 virus encoded 4 or 5 amino acid changes in the spike protein plus additional protein changes in nsp3, nsp6, ORF8 and the ORF9.

A plot of nucleotide changes over time for Ugandan line A viruses showed a consistent evolutionary rate of about 2 nucleotide change per month observed for SARS-CoV-2 throughout the pandemic. “

All organisms mutate. Viruses appear to have the highest mutation rates per base pair per generation. This study reports the emergence and spread of a novel SARS-CoV-2 variant of the A-line (A.23.1) with multiple protein changes throughout the viral genome.

The spread of a new variant with increased transmissibility and / or virulence can put more pressure on the healthcare system – and ultimately result in a higher mortality rate. There is also a risk that new variants may undermine current vaccines and therapies aimed at preventing or reducing COVID-19 based on previous strains.

From a screening of the SARS-CoV-2 genomic data from GISAID, the researchers saw that the A.23 and A.23.1 sublines are now circulating in 12 countries outside Uganda (from Africa, Asia, Europe, North America and Oceania); this indicates the worldwide movement of the newly emerging variants.

This study also emphasizes the importance of rapid genomic surveillance of infectious pathogens as well as the need to closely monitor virus movements. Significant changes observed in the spike protein – which may affect transmission, infection and immune selection – are crucial to understand the evolution of the virus and warrant additional studies of its functional consequences.

Although the clinical impact of the A.23.1 variant is not yet clear, it is essential to continue careful monitoring of this variant, as well as a rapid assessment of the impact of the changes in the spike protein on vaccine efficacy. “

*Important announcement

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