Wednesday, January 06, 2021

Argentina: PAIS Report On COVID E484K Variant In South America

 



#15,687

Over the past 48 hours Argentine media has been filled with reports of a new COVID variant which has been picked up by PAIS (Proyecto Argentino Interinstitucional de genómica de SARS-CoV-2), which carries one of the mutations (E484K in the spike protein) also found in the 501Y.V2 variant which was first picked up in South Africa. 

This E484K mutation has been linked to reduced antibody recognition, which may decrease immune protection acquired from prior infection or vaccination. You'll find an excellent twitter thread from Bloom Labs on the potential ramifications here

While too little is known about this South American variant to even speculate as to its potential impact, we do have the following report from PAIS, describing their initial findings.  I've translated an except, but you'll want to follow the link to read it in its entirety. 

Report N ° 10: Active surveillance of variants of SARS-COV-2 in the city of Buenos Aires, Greater Buenos Aires and the city of Santa Fe.

01/03/2021

The emergence of viral variants is a natural process in the evolution of viruses. However, when these occur with genetic changes in regions involved in the interaction with the cell receptor or in the recognition of specific antibodies, it is necessary to evaluate the possible impact of these genetic changes on viral spread, the ability to cause more severe disease or the response to vaccination.

During the last weeks, three viral variants of SARS-CoV-2 have attracted the attention of the scientific community and national governments:
● The variant VOC 202012/01 (lineage B.1.1.7), whose most recent sample was detected in the UK on 09/20/2020 (previously named “VUI 202012/01 ", or informally as" new strain "," London variant ", "UK variant", "20B / 501Y.V1 (UK variant)") (Rambaut et al., 2020). This variant has already been reported as of January 3, 2021 in 23 countries including Brazil, Chile, Canada and the United States within America.

● Variant 501Y.V2 (lineage B.1.351), detected in South Africa since 10/08/2020, also known as “South Africa variant”, “SA variant” or “20C / 501Y.V2 (South Africa variant) ”(Tegally et al., 2020). This variant has been reported first in South Africa, and then in Switzerland, the United Kingdom and Finland.

● The Rio de Janeiro variant (derived from lineage B.1.1.28), detected Rio de Janeiro, Brazil, since October 2020 (Voloch et al., 2020).
Importantly, while some variants share genetic changes (such as the S_N501Y mutation shared between the VOC 202012/01 and 501Y.V2 variants, or the S_E484K mutation shared between the 501Y.V2 and Rio de Janeiro variants),  these viral variants have different origins, that is, those common changes they occurred in independent evolutionary events.
(SNIP)
Results:
In none of the 105 SARS-CoV-2 sequences (total or partial) was the S_N501Y mutation characteristic of UK VOC202012 / 01 or UK 501Y.V2 variants South Africa. There were also no other changes typical of the VOC202012 / 01 variant. in the S gene. However, the presence of the S_E484K mutation was observed in one of the 105 sequences (sample from GBA). It is one of the three mutations marker of the South African variant, and it is also found as the only mutation of the gen S in the Rio de Janeiro variant.
Although the find is interesting, it requires sequencing the entire SARS-CoV-2 genome to determine if the virus found in GBA shares a common origin with the Rio de Janeiro variant.
Residue 484 of protein S is located in the receptor-binding motif (RBM) and interacts directly with the human hACE2 receptor (Lan et al., 2020). The S_E484K mutation is present in the 501Y.V2 variant (South Africa) and in the Rio de Janeiro, but it is rare worldwide and showed signs of being associated with host adaptation (Tegally et al, 2020). This mutation was also associated with resistance to neutralization by neutralizing monoclonal antibodies and sera convalescent polyclonal (Weisblum et al., 2020; Liu et al., 2020, Baum et al., 2020).
 Conclusion:
Since active surveillance of the SARS-CoV-2 variants of interest began (12/14/20 to 12/26/20), out of a total of 144 samples sequenced from CABA, GBA and the city of Santa Fe (39 of report N ° 9 and 105 of the current one), it has not yet been detected none of the protein S marker changes of variant VOC202012 / 01 (UK), while in five samples the change S_E484K was detected (from CABA and GBA). This mutation is present in both the 501Y.V2 variant (South Africa) -together with two other marker mutations in Spike- and in the Rio de Janeiro variant -as only marker mutation in Spike-.
We consider that the increase in positivity of cases that is occurring in different regions of the country requires continuing to actively monitor these variants and others that could arise. Likewise, the maintenance of social distancing measures, the use of masks, the correct ventilation of the rooms, and the washing of hands frequent, it must be fulfilled, regardless of which variant is circulating in the population, taking into account that these measures will decrease viral circulation, prevent infection and death and, at the molecular level, decrease the possibility of emergence of new variants.
The Argentine Interinstitutional Consortium for SARS-CoV-2 Genomics will continue performing real-time molecular surveillance on circulation cases community with the proposed strategy, while continuing to characterize the SARS-CoV-2 genomes circulating in different regions of the country in order to determine if these variants entered before the restrictive measures taken in the last weeks of 2020, or if new local viral variants have emerged. 
(Continue . . . )


Even assuming the E484K mutation helps to evade the vaccine, for this Argentine variant to pose a serious threat, it would need to have enhanced transmissibility on par with the B.1.1.7 or 501Y.V2 variants already making inroads around the globe. 

And right now, we don't have evidence of that.  But it is something we'll be watching.  

What  this study does show is that troublesome mutations - like E484K - can occur independently in multiple locations around the world. That the South African variant wasn't a fluke. 

Which suggests we'll be seeing more variants of concern emerge in the months ahead.