New SARS-CoV-2 Variant Of Concern Deemed As Being More Lethal Identified In Uganda-The A.23.1 Variant

Researchers from Uganda and the United Kingdom have identified a new SARS-CoV-2 variant of concern deemed as being more lethal that is currently circulating in Uganda.


 
The study team comprising of researchers from the MRC/UVRI & LSHTM Uganda Research Unit-Uganda, the Central Public Health Laboratories of the Republic of Uganda, the  Institute for Evolutionary Biology, University of Edinburgh-UK,  Uganda Virus Research Institute, MRC University of Glasgow Centre for Virus Research-UK and the EMC, Rotterdam-Netherland report the newly emerging A sub-lineages, A.23 and A.23.1, encoding replacements in the spike protein, nsp6, ORF8 and ORF9, with A.23.1 the major virus lineage now observed in Kampala.
 
It was found that most lethal cases reported in Uganda belonged to this new A.23.1 Variant.
 
The study findings were published on a preprint server and are currently being peer reviewed. https://www.medrxiv.org/content/10.1101/2021.02.08.21251393v1
 
The pathogen of the COVID-19 disease ie the SARS-CoV-2 coronavirus was first identified in Wuhan, China, in December 2019. Since then, the virus has infected more than 109 million people worldwide and caused over 2.41 million deaths. Due to its high transmissibility, it has been difficult to contain the virus in an epidemic region.
 
However towards the latter part of 2020, a new variant of SARS-CoV-2 (lineage B.1.1.7) emerged in England along with another one, (B.1.351), also known as 501Y.V2, in South Africa. Both of which are observed to have heightened transmissibility, with some early studies even suggesting an increase in virulence in these mutations.
 
Since many more variants of concern are appearing globally including the P.1 variant that is now causing a major crisis in Brazil.
 
Alarmingly in a concerning new development, the  interdisciplinary research team from Uganda and the UK report the emergence and spread of a new SARS-CoV-2 variant of the A lineage with multiple protein changes throughout the viral genome.
 
The study team report the emerging A sub-lineages, A.23 and A.23.1 of the SARS-COV-2.
 
The study team reports the A.23.1 sub-lineage to be the major virus lineage now observed in the Kampala region in Uganda. This sub-lineage is reported to encode 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 lineage B variants of concern (VOCs).
 
It was reported that the Kampala region has become an epicenter of viral transmission in the country; 60-80% of the country’s new cases daily have been identified there, from June 2020 to January 2021.
 
The study team generated the SARS-CoV-2 genomic sequence data to monitor virus movement and changes thereof.
 
The team also report that across the entire region’s epidemic, 39% of the strains can be classified as the major B lineage, whereas 61% are within the A lineage.
 
Interestingly, when the transportation was characterized by land travel (primarily t ruck drivers’ movements) and no flights, the lineage B.1 strains predominated. Over the course of their study, however, the researchers unexpectedly found that, almost exclusively, the A lineage viruses are found in the Kampala region up to late January 2021.
 
As a result of the researchers identifying the lineage A strain as originating from a truck driver (strain UG053) as basal to the newly emergent A.23 variant, they recommend continuous monitoring of all truck drivers transiting into and out of Uganda. This will help to better understand the inland cross-country entry and exit, and circulation of the strains in this region, where (large scale) genomic surveillance is still not exhaustive.
 
Significantly, the genome sequences from 6 lethal Ugandan cases belonged to two lineages A.25 and B.1.393. While the SARS-CoV-2 lineage A is less prevalent than lineage B in Europe, the UK and the USA, the presence of lineage A viruses from lethal community cases throughout Uganda indicates that this lineage is circulating in the country and is capable of severe infection.
 
In order to monitor the epidemic in more detail, the researchers generated the full genome SARS-CoV-2 sequences from SARS-CoV-2 positive samples in Uganda. From this analysis, the researchers present a maximum-likelihood phylogenetic tree comparing all available complete and high-coverage Uganda sequences.
 
Numerous variant lineages were observed at low frequencies and only briefly and may have undergone apparent extinction, similar to patterns observed in the UK and Scotland, the researchers write.
 
The study team also found that the SARS-CoV-2 outbreaks in and around the prisons to be the lineage A.23, with three amino acid (aa) changes encoded in the exposed S1 domain of the spike protein (F157L, V367F, and Q613H).
 
Continued circulation and evolution of A.23 in Uganda was observed and two additional changes in spike R102I and P681R were observed in December 2020 in Kampala; these SNPs define the sub-lineage A.23.1.
 
However the A.23.1 virus’s sequence encoded 4 or 5 amino acid changes in the spike protein plus additional protein changes in nsp3, nsp6, ORF8, and the ORF9.
 
Additional changes in non-spike regions also define the A.23 and A.23.1, including nsp3: E95K, nsp6: M86I, 198 L98F, ORF 8: L84S, E92K and ORF9 N: S202N, Q418H. These new lineages can be assigned since pangolin version v2.1.10 and pangoLEARN data release 2021-02-01.
 
Interestingly a plot of nucleotide changes over time for the Ugandan lineage A viruses showed a consistent evolutionary rate of roughly 2 nucleotide change per month that has been observed for SARS-CoV-2 throughout the pandemic.
 
Viruses are found to have the highest per base pair per generation mutation rates. This study reports the emergence and spread of a new SARS-CoV-2 variant of the A lineage (A.23.1) with multiple protein changes throughout the viral genome.
 
The study team warns that the spread of a new variant with heightened transmissibility and/or virulence can place 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 mitigating COVID-19, based on earlier strains.
 
It was also noted by the study team that from a screening of the SARS-CoV-2 genomic data from GISAID, it was observed that the A.23 and A.23.1 sub-lineages are now circulating in 12 countries outside of Uganda (from Africa, Asia, Europe, North America and Oceania); this indicates the global movement of the newly emerging variants.
 
The study also highlights the importance of rapid genomic surveillance of infectious pathogens and also the need to closely monitor the virus’s evolution. Significant changes observed in the spike protein that may impact the transmission, infection, and immune selection are crucial to understanding the evolution of the virus and warrant additional studies on the functional consequences.
 
Though 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 consequences of the spike protein changes for vaccine efficacy.
 
For more on the A.23.1 Variant, keep on logging to Thailand Medical News