University of Oxford Study Of SARS-CoV-2 B.1.17 Variant Shows That N501Y Mutation Causes Higher Viral Loads
: Scientist from University of Oxford in a news study have found that the N501Y mutation found on the SARS-CoV-2 B.1.17 variant possibly causes a higher viral load in those infected with the variant.
The B.1.1.7 variant also called VUI-202012/01 has emerged which is increasing in frequency, primarily in the South East of England
One potential hypothesis is that infection with the new variant results in higher viral loads, which in turn may make the virus more transmissible.
The study team found higher (sequence derived) viral loads in samples from individuals infected with the new variant with median inferred viral loads was three-fold higher in individuals with the new variant. Most of the new variants were sampled in Kent and Greater London.
The team observed higher viral loads in Kent compared to Greater London for both the new variant and other circulating lineages. Outside Greater London, the variant has higher viral loads, whereas within Greater London, the new variant does not have significantly higher viral loads compared to other circulating lineages. Higher variant viral loads outside Greater London could be due to demographic effects, such as a faster variant growth rate compared to other lineages or concentration in particular age-groups.
However, their analysis does not exclude a causal link between infection with the new variant and higher viral loads. This is a preliminary analysis and further work is needed to investigate any potential causal link between infection with this new variant and higher viral loads, and whether this results in higher transmissibility, severity of infection, or affects relative rates of symptomatic and asymptomatic infection.
The study findings were published on a preprint server and are currently being peer reviewed. https://www.medrxiv.org/content/10.1101/2021.01.12.20249080v1
The alarming emergence of new SARS-CoV-2 variants has been of grave concern to public health authorities and governments involved in stopping the ongoing pandemic of COVID-19.
The B.1.1.7 variant was first documented on December 14, 2021, and is defined by the N501Y mutation in the receptor-binding domain (RBD) of the spike protein, the deletion ΔH69/V70, and many other mutations.
Importantly it has recently been reported that this variant is rising in frequency in the South-east of England so fast as to raise the suspicion that it has increased transmissibility.
This study aimed to investigate this aspect of the virus in terms of increased viral load.
The study team sequenced all positive samples from four Lighthouse laboratories in the UK, using their quantitative sequencing approach. This yields the number of unique mapped reads, which bears a correlation with and therefore acts as a proxy for the viral load.
The team found that the logarithm of unique mapped reads was negatively correlated with the Ct values obtained from the polymerase chain reaction (PCR) testing.
The study team selected the presence of Y501 as a marker of the new variant. From 88 samples that showed this mutation, they considered only t
he samples taken in the period from October 31 to November 13, 2020. This showed that the number of unique mapped reads in the Y501 variant was more significant than in the N501 variant, indicating that the median viral loads are increased by about three times for the Y501 variant.
The team then examined the geographical location from which different samples were taken, where such information was available.
They found that whichever variant was present, all samples from Greater London had a much higher viral load compared to any other location.
However at other locations, the viral loads for Y501 were much higher compared to N501. Significantly, however, the location, which was enriched for Y501, Kent county, did not show any difference between Y501 and N501 with respect to viral loads. This could indicate that the infection with VUI-202012/01 and the viral load were correlated outside Greater London. In the latter location, the reasons for the lack of association could be because the study was underpowered, or alternatively, it could be due to differences in the demographic and epidemiologic parameters of the London population relative to other locations.
The study team points out that the samples in this study came from people who were symptomatic. The viral loads are thought to be higher at the start of symptoms.
As the sequenced data covered a broad range of viral loads, they suggest that the test data came from individuals at all stages of symptomatic infection.
Interestingly the new variant may be circulating in a particular age group, for instance, which has higher viral loads. This may be one explanation for the difference in Ct-viral load correlations in Greater London vs. outside this region.
Another factor is the intense transmission that occurs during the initial phase of an epidemic caused by a given lineage. Dispersion of the lineage occurs much later. This can be confirmed only with more research.
However the reasons for the faster growth associated with this variant are not clear: it could be due to faster epidemic growth, demographic patterns, founder effects, or higher viral loads, among other biological mechanisms.
Importantly the correlation with higher viral loads, in this case, seems to suggest increased transmissibility of this virus, but further studies are required. Again, the N501Y mutation may not be the only reason for this expansion. There is more need to understand how viral levels are related to virulence since this may determine the infection's severity.
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