When the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is the virus responsible for the coronavirus disease of 2019 (COVID-19), first spread throughout the world, a variety of governments were forced into implementing expensive and restrictive measures to stop the risk of transmission. These measures often consisted of mandatory mask-wearing, the closing of public spaces, and even full lockdowns/stay-at-home orders.
Study Introduction and rapid dissemination SARS-CoV-2 Gamma Varant of Concern in Venezuela. Image credit: Droneandy/Shutterstock.com
When the first COVID-19 vaccines became available and mass vaccination programs started to show some promise, these restrictive measures were rescinded in order to allow economies to recover. However there have been a number of SARS-CoV-2 variants that have been of concern (VOCs) that have proven to be able to provide protection against vaccines and continue infecting people.
SARS-CoV-2 spike proteins consist of two subunits, the S1 and the S2 that must be cut with the host protein. The S1 subunit contains a receptor-binding domain (RBD) that binds to the angiotensin-converting enzyme 2 (ACE2) receptor present on the host cell in order to permit viral cell entry, while the S2 subunit is responsible for membrane fusion. Neutralizing antibodies and vaccines usually target the RBD to block entry into cells; however there are many VOCs that have mutations in this area which can allow them to evade immune activity.
About the study
In a recent study published in the journal Infection, Genetics and Evolution, researchers from the Instituto Venezolano de Investigaciones Cientifica study the introduction of one of the VOCs into Venezuela.
To assess the spread of SARS-CoV-2 Gamma Oc in Venezuela Researchers collected nasal swabs from those who had been positive for the virus at routine diagnosis. The samples were selected for complete genome sequencing. The alignment of the sequences was then performed and phylogenetic analysis. The Student t-test, Fisher Exact and Chi-Square tests with Yates correction were used to determine the statistical significance of the differences.
The researchers developed a partial sequencing methodology to allow a large number of samples to be screened to identify different variants. The initial screening consisted of a simple two-round polymerase chain reaction (PCR) amplification to analyze a fragment of the spike protein which is typically associated with key mutations.
Of the 245 isolates that amplified successfully, 29 contained both E484K and N501Y, and one was only E484K. Around 25% of samples did not amplify, which could be due to issues with the samples’ integrity.
Once the VOCs were detected, another round of reverse-transcriptase PCR (RT-PCR) was used to amplify a smaller fragment of the spike protein, in which the mutations that are specifically associated with the Gamma VOC could be found. Researchers did not find any difference in the Gamma VOC prevalence between symptomatic and asymptomatic patients.
In total 16 complete genomes from the Gamma VOC were isolated, with more than 99.9 percent similarity. The first of these genomes were discovered at end January 2021. However, the rate of discovery grew quickly after that point. In certain areas of the country, 95% of tested isolates were of the Gamma VOC by March 2021.
Scientists also looked at vaccine breakthrough infections that could have been further infected. While not all cases were caused by the Gamma VOC mutation however, all cases showed the E484K variant. This mutation was also discovered more often among isolates of non-variants of concern.
In a thorough review of the recent literature, the researchers uncovered the number of cases of reinfection. These cases were similar or less severe than the prior infection, and had distinct lineages from the first. The majority of reinfection cases with E484K were identified in South America, and reinfection could occur in as little as 24 days after the initial infection.
The authors of the study are focused on sequencing the smallest possible amount of the genome, making it possible to process a much larger amount of samples than is normal. Although the presence of mutations in specific amino acid sites does not necessarily mean that the VOC of concern was present, the identification and subsequent examination of these mutations helped researchers to quickly identify the introduction of the Gamma VOC.
It took only two months for Gamma VOC, the dominant strain, to become popular in the country. Furthermore, the rapid emergence and dominance in Manaus prior to this show that this variant can spread and prevaricate rapidly.
As one of the VOCs that can evade vaccine-induced and natural immunity, the speed that this variant is spreading is worrying. The research presented here could allow for more rapid detection of SARS-CoV-2 VOCs from other countries, thereby providing invaluable information for public health policy makers and epidemiologists.
- Jaspe, R. C., Loureiro, C. L., Sulbaran, Y., et al. (2021). Introduction and rapid distribution of SARS-CoV-2 Gamma Variant of Concern in Venezuela. Infection, Genetics and Evolution. doi:10.1016/j.meegid.2021.105147.
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