Researchers report worrying new variant of SARS-CoV-2 in Uganda

The etiologic agent of coronavirus disease 2019 (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 its high transmissibility, it has been difficult to contain the virus in an epidemic region.

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

In a disturbing new development, an interdisciplinary research team from Uganda and the United Kingdom report the emergence and spread of a new variant of SARS-CoV-2 of the A lineage with multiple protein changes throughout the genome viral. The researchers recently published their findings in a pre-print on the medRxiv * server.

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

The research team reports that the A.23.1 subline is the main viral lineage now observed in the Kampala region of Uganda. This subline is reported to encode several spike proteins, nsp6 (non-structural protein), ORF8 and ORF9 (open reading frames 8 and 9) protein changes. Some of these replacements are expected to be functionally similar to those seen in the B-line variants of concern (VOCs).

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

The researchers also report that across the region’s epidemic, 39% of strains can be classified as the major B line, while 61% belong to the A line. Interestingly, when transport was characterized by land movements (mainly trucker movements) and the absence of theft, strains of the B.1 lineage predominated. During their study, however, the researchers unexpectedly discovered that almost exclusively A-lineage viruses were found in the Kampala region until the end of January 2021.

Because the researchers identify the A line strain as originating from a truck driver (strain UG053) as basal to the newly emerging variant A.23, they recommend continued monitoring of all truck drivers transiting to and from the ‘Uganda. This will help to better understand the entry and exit from one country to another as well as the circulation of strains in this region, where genomic surveillance (on a large scale) is still not exhaustive.

In particular, the genomic sequences of 6 Ugandan lethal cases belonged to two lines A.25 and B.1.393. While the SARS-CoV-2 A lineage is less prevalent than the B lineage in Europe, the UK and the US, the presence of A lineage virus from fatal cases across Uganda indicates that this line circulates in the country and is capable of infection.

To monitor the outbreak in more detail, the researchers generated the full genome sequences of SARS-CoV-2 from SARS-CoV-2 positive samples in Uganda. From this analysis, the researchers present a maximum likelihood phylogenetic tree comparing all the sequences available in Uganda that are complete and high coverage.

Several variant lines have been observed at low frequencies and only briefly and may have undergone apparent extinction, 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 prisons were the A.23 lineage, with three amino acid changes (aa) encoded in the exposed S1 domain of the spike protein (F157L, V367F and Q613H).

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

A graph of nucleotide changes over time for the Ugandan A lineage viruses showed a constant rate of evolution of approximately 2 nucleotide changes per month which was observed for SARS-CoV-2 throughout. the pandemic.

All organisms mutate. Viruses have the highest base pair mutation rates per generation. This study reports the emergence and spread of a new variant of SARS-CoV-2 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 strain on the healthcare system – and ultimately lead to a higher death rate. There is also a risk that new variants will compromise current vaccines and therapies, aimed at preventing or mitigating COVID-19, based on earlier strains.

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

This study also highlights the importance of rapid genomic surveillance of infectious pathogens as well as the need to closely monitor the movements of the virus. The significant changes observed in the spike protein – which may impact transmission, infection and immune selection – are crucial to understanding the evolution of the virus and warrant further studies on the functional consequences.

Although the clinical impact of variant A.23.1 is not yet clear, it is essential to continue to carefully monitor this variant, as well as a rapid assessment of the consequences of advanced protein changes on vaccine efficacy. “

*Important Notice

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