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

The aetiological 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 is difficult to contain the virus in an epidemic region.

At the end of 2020, a new variant of SARS-CoV-2 (strain B.1.1.7) appeared in England and another, (B.1.351), also known as 501Y.V2, in South Africa. It was observed that both have high transmissibility, with some initial studies even suggesting an increase in the virulence of these mutations.

In a worrying new development, an interdisciplinary research team from Uganda and the UK reported the emergence and spread of a new variant of strain A SARS-CoV-2 with several protein changes across the viral genome. The researchers recently released their findings in a prepress on the medRxiv * server.

Study: A variant of the strain SARS-CoV-2 (A.23.1) with an altered peak has emerged and is dominating the current Uganda epidemic.  Image credit: iunewind / Shutterstock

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

The research team reports that sub-lineage A.23.1 is the main strain of virus now seen in the Kampala region of Uganda. This sub-lineage is reported to encode various peak proteins, nsp6 (non-structural protein), ORF8 and ORF9 (open reading frames 8 and 9) protein changes. Some of these substitutions are expected to be functionally similar to those seen in the worrying variants of strain B (VOCs).

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

Researchers also report that across the region’s epidemic, 39% of the strains can be classified as the main strain B, while 61% are within strain A. Interestingly, when transportation was characterized by land travel (mainly trucker movements) and no flight, strains of lineage B.1 predominated. In the course of the study, however, the researchers unexpectedly discovered that, almost exclusively, strain A viruses were found in the Kampala region by the end of January 2021.

As the researchers identified the strain of strain A as originating from a truck driver (strain UG053) as baseline for the newly emerging variant A.23, they recommend continuous monitoring of all truck drivers in transit to and from Uganda. This will help to better understand the entry and exit of cross-country inland and the circulation of strains in this region, where genomic surveillance (on a large scale) is not yet exhaustive.

Notably, the genome sequences of 6 Ugandan lethal cases belonged to two strains A.25 and B.1.393. Although strain A SARS-CoV-2 is less prevalent than strain B in Europe, the UK and the USA, the presence of strain A viruses in lethal cases in the community in Uganda indicates that this strain is circulating in the country and is capable of serious infection.

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

Several variant strains have been observed at low frequencies and only briefly and may have undergone an apparent extinction, similar to patterns seen in the United Kingdom and Scotland, the researchers write.

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

Whereas the A.23.1 virus sequence encodes 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 Uganda strain A viruses showed a consistent evolutionary rate of change of approximately 2 nucleotides per month that was observed for SARS-CoV-2 during the pandemic ”.

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

The spread of a new variant with greater transmissibility and / or virulence can put more pressure on the health care system – and, ultimately, result in a higher mortality rate. There is also a risk that new variants could harm current vaccines and therapies, designed to prevent or mitigate COVID-19, based on previous strains.

From a screening of GISAID’s SARS-CoV-2 genomic data, the researchers noted that sub-strains A.23 and A.23.1 are now circulating in 12 countries outside Uganda (Africa, Asia, Europe, South America) North and Oceania); this indicates the global movement of the new emerging variants.

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

Although the clinical impact of variant A.23.1 is still unclear, it is essential to continue careful monitoring of this variant, as well as a quick assessment of the consequences of peak protein changes for vaccine efficacy. “

* Important news

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

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