While global vaccination campaigns are increasing and reaching interesting results, in particular in Israel, the Emirates and the UK, Sars-CoV-2 is “evolving” by showing an increased number of strains that may affect not only the virus ability to spread among the population, but also its ability to escape from the developed neutralizing antibodies.
New Covid Variants
If mutations are a common way for viruses, in particular the RNA ones, to respond to selective pressures, the occurrence in a pandemic virus like COVID-19 cause new challenges to the Public Health systems that are starting to succeed in fighting the “original” strain.
Mutations can obviously occur in multiple regions of the viral RNA, however some of them are of interest due to their ability to gain power to Sars-CoV-2.
Among the crucial ones, the mutations at the S gene coding sequence, may impact the ability of the Virus to spread and escape to the actual proposed solutions.
United Kingdom – UK variant
In the United Kingdom (UK), a new variant of SARS-CoV-2 (known as 20I/501Y.V1, VOC 202012/01, or B.1.1.7) emerged with a large number of mutations.
In particular the N501Y is the mutation that defines the variant as VOC (Variant of Concern) due to the enormous clinical impact of its presence, such asgreater stability of ACE2-Spike interaction in the RBD region (4) and a lower activity of neutralizing antibodies (5).
Another of the mutations in the VOC 202012/01 variant, the deletion at position 69/70 was found to affect the performance of some diagnostic PCR assays with an S gene target. Most PCR assays in use worldwide will use multiple targets and therefore the impact of the variant on diagnostics is not anticipated to be significant.
Preliminary reports by the United Kingdom inferred how VOC 202012/01 is more transmissible than previous circulating forms, with an estimated increase of between 40% and 70% in transmissibility. To date the prevalence is attested to 20- 25% of the Sars-CoV-2 (https://www.who.int/csr/don/21-december-2020-sars-cov2-variant-united-kingdom/en).
As of 9th of February, VOC-202012/01 variant has been reported in 86 other countries/territories/areas (https://www.who.int/publications/m/item/weekly-epidemiological-update—9-february-2021) in five of the six WHO regions.
South Africa – SA variant
In South Africa, another variant of SARS-CoV-2 (known as 20H/501Y.V2 or B.1.351) emerged independently of B.1.1.7.
On December 18, national authorities in South Africa announced the detection of a new variant of SARS-CoV-2 that is rapidly spreading in three provinces of South Africa. South Africa has named this variant 501Y.V2, because of a N501Y mutation but it is characterized by the presence also of the E484K one.
This variant has multiple mutations in the spike protein, including K417N, E484K, N501Y. Unlike the B.1.1.7 lineage detected in the UK; this variant does not contain the deletion at 69/70. Some evidence indicate that one of the main spike protein mutations, E484K, may affect neutralization by some polyclonal and monoclonal antibodies.
Cases attributed to this variant have been detected in more than 44 countries outside of South Africa (https://www.who.int/publications/m/item/weekly-epidemiological-update—9-february2021). This variant was reported in the US and other countries at the end of January 2021.
Brazil – BR variant
In Brazil, a variant of SARS-CoV-2 (known as P.1) emerged that was first was identified in four travellers from Brazil, who were tested during routine screening at Haneda airport outside Tokyo, Japan.
This variant has 17 unique mutations, including three in the receptor binding domain of the spike protein. This variant was detected in the US at the end of January 2021. Up to date it was probed in 15 countries world wide (https://www.who.int/publications/m/item/weeklyepidemiological-update—9-february-2021).
Additionally, to the P1 variant, another, and potentially more important has been referred to contains the S protein mutation E484K and was first detected in sequences from patients in Rio de Janeiro state, collected in October 2020, but based on phylogenetic analysis the variant likely originated in July 2020.5: 484 K.V2 or P2.
This 484 K.V2 variant has since spread to multiple other countries including: England, Singapore, the USA, Norway, Argentina, Denmark, Ireland and Canada The E484K mutation in particular is of interest due to evidence that it may allow immune escape.
Why is it important to detect variants?
Some of the potential consequences of emerging variants are the following:
- Ability to spread more quickly in people. There is already evidence that one mutation, D614G, confers increased ability to spread more quickly than the wild-type[2] SARS-CoV-2. In the laboratory, 614G variants propagate more quickly in human respiratory epithelial cells, outcompeting 614D viruses. There also is epidemiologic evidence that the 614G variant spreads more quickly than viruses without the mutation.
- Ability to cause either milder or more severe disease in people. In January 2021, experts in the UK reported that B.1.1.7 variant may be associated with an increased risk of death compared to other variants. More studies are needed to confirm this finding.
- Ability to evade detection by specific viral diagnostic tests. Most commercial reversetranscription polymerase chain reaction (RT-PCR)-based tests have multiple targets to detect the virus, such that even if a mutation impacts one of the targets, the other RT-PCR targets will still work.
- Decreased susceptibility to therapeutic agents such as monoclonal antibodies.
- Ability to evade natural or vaccine-induced immunity. Both vaccination against and natural infection with SARS-CoV-2 produce a “polyclonal” response that targets several parts of the spike protein. The virus would likely need to accumulate multiple mutations in the spike protein to evade immunity induced by vaccines or by natural infection.
Among these possibilities, the last—the ability to evade vaccine-induced immunity—would likely be the most concerning because once a large proportion of the population is vaccinated, there will be immune pressure that could favour and accelerate emergence of such variants by selecting for “escape mutants.”
Up to date, there is no evidence that this is occurring, and most experts believe escape mutants are unlikely to emerge because of the nature of the virus.
What are the actual ways to detect variants and why they are not efficient in a pandemic situation?
Nowadays variants can be analysed mainly in 3 ways:
- Sanger Sequencing
- NGS
- RT-PCR (multiplex or by using melting analysis).
Almost all of them not only are a second level test (that occurs after a first test to confirm the positivity to the COVID-19), but harbour several limits:
- High expensive instrument is needed
- Specific personnel training
- Longer time to get a result
- Cost improvement
Moreover, actual multiplex tests require to use more than 1 tube/patients, directly impact both labs‘ productivity and reports TAT.
What is the value of the New COVID-19 PCR detection kit?
With the scope to provide new tools to labs in fighting pandemic, OaCP has developed a new type of PCR kit able to simultaneously detect both the COVID-19 “original” strain and the UK, South African and Brazilian P2 Variants.
This test has been designed to provide the maximum compatibility with the actual RT-PCR machines making possible to every lab, also the smallest one, to perform a high sensitive, high valuable test.
Written by Dr. Enrico Di Oto, BS, MD, PhD, OaCP CEO and Dr. Simone Di Giacomo, BS, PhD, OaCP R&D manager
References:
1 SARS-CoV-2-variant-multiple-spike-protein-mutations-United-Kingdom, European Centre for Disease Prevention and Control, Stockholm, 2020.
https://www.ecdc.europa.eu/sites/default/files/documents/SARS-CoV-2-variant-multiple-spikeprotein-mutations-United-Kingdom.pdf.
2 Science Brief: Emerging SARS-CoV-2 Variants, CDC, Jan. 28, 2021. https://www.cdc.gov/coronavirus/2019-ncov/more/science-and-research/scientific-briefemerging-variants.html
3 WHO _ SARS-CoV-2 Variants, Disease Outbreak News, WHO, 31 December 2020. https://www.who.int/csr/don/31-december-2020-sars-cov2-variants/en
4 Mutation N501Y in RBD of Spike Protein Strengthens the Interaction between COVID-19 and its Receptor ACE2.
Fang Tian et al. bioRxiv 2021.02.14.431117; doi: https://doi.org/10.1101/2021.02.14.431117 https://www.biorxiv.org/content/10.1101/2021.02.14.431117v2.abstract
5 Reduced neutralization of SARS-CoV-2 B.1.1.7 variant by convalescent and vaccine sera, Piyada Supasa et al, Cell, 2021, ISSN 0092-8674, https://doi.org/10.1016/j.cell.2021.02.033 https://www.sciencedirect.com/science/article/pii/S0092867421002221
6 Early transmissibility assessment of the N501Y mutant strains of SARS-CoV-2 in the United Kingdom, Leung K et al. October to November 2020. Euro Surveill. 2021 Jan;26(1):2002106. doi: 10.2807/1560-7917.ES.2020.26.1.2002106. PMID: 33413740; PMCID: PMC7791602. https://pubmed.ncbi.nlm.nih.gov/33413740
7 WHO _ SARS-CoV-2 Variant – United Kingdom of Great Britain and Northern Ireland, WHO, 21 December 2020. https://www.who.int/csr/don/21-december-2020-sars-cov2-variant-united-kingdom/en
8 Structural genetics of circulating variants affecting the SARS-CoV-2 spike/human ACE2 complex, Francesco Ortuso et al. (2021) Journal of Biomolecular Structure and Dynamics, DOI: 10.1080/07391102.2021.1886175. https://www.tandfonline.com/doi/citedby/10.1080/07391102.2021.1886175?scroll=top&needAccess=true
9 Resurgence of COVID-19 in Manaus, Brazil, despite high seroprevalence, Sabino et al. The Lancet, volume 397, issue 10273, p452-455, february 06, 2021, DOI: https://doi.org/10.1016/S0140-6736(21)00183-5 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00183-5/fulltext
10 Introduction of Brazilian SARS-CoV-2 484K.V2 related variants into the UK. Toovey OTR, Harvey KN, Bird PW, Tang JWW. J Infect. 2021 Feb 3:S0163-4453(21)00047-5. doi: 10.1016/j.jinf.2021.01.025. Epub ahead of print. PMID: 33548358; PMCID: PMC7857057. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857057
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