The UK, South African and Brazilian variants float like specters over our (precious few) certainties. Could these variants reduce the reliability of molecular testing or the efficacy of vaccines? Should we expect more variants in the future?

Since we became acquainted with SARS-CoV-2, thousands of mutations have been identified through the sequencing of the virus. The mutations are widespread throughout the virus; which, let’s remember, is just over 29,000 bases long, 29,000 bricks that carry the genetic information necessary for its survival, once it’s introduced itself into a mammalian cell — be it human or animal.

Before speaking about the consequences caused by the UK, South African and Brazilian variants, it’s necessary to clarify some terms, often used as synonyms, but they’re not synonyms: “mutation” and “variant”.

Let’s start by stating that once an RNA virus, in the specific case SARS-CoV-2, infects a cell, the first thing it does is to use the host cell to produce copies of itself; this is its way of reproducing.

This “copying system” isn’t always perfect and occasionally there may be differences between the original RNA copy and the new copy; these differences are called mutations. Thousands of mutations have been identified by sequencing the genetic code of the virus present in infected human patients. Very often mutations have no effect (or a negative effect) on the virus itself, and in some cases, they can be favorable for the survival of SARS-CoV-2.

How does a Virus survive? By changing!

The set of some mutations that are shared between humans infected by Coronavirus, are called variants and generate a new viral strain that will always be called SARS-CoV-2 but clearly distinguishable from the original viral strain. The variants that spread must necessarily bring some sort of benefit to the virus, and usually it’s an increased ability to survive and greater transmissibility, or adaptability to the environment in which the Coronavirus lives. From an evolutionary point of view, the variants that are more lethal don’t survive for long, since they kill the host that allows them to reproduce.

What are the characteristics of the UK, South African, and Brazilian variants?

UK variant

It’s also called B.1.1.7 or Kent variant, since it was first identified in the Southeast of England. There are 23 mutations that characterize this variant and 8 of them are located in the region encoding the Spike protein; the part of the virus that binds to receptors on the surface of human cells and allows SARS-CoV-2 to enter the cells. From currently available observations, this variant binds more efficiently to the human ACE-2 receptor and thus increases the virus’ ability to spread. The B.1.1.7 strain has rapidly spread to the rest of England and beyond, due to its increased transmissibility. While more contagious, variant B.1.1.7 doesn’t appear to be more virulent (i.e. lead to more severe symptoms or have higher lethality); the parameters measured as being periods of hospitalization and deaths caused by SARS-CoV-2.

South Africa variant

It’s known as variant 501Y.V2 or strain B.1.351 and was first identified in South Africa. Overall, the South African variant is characterized by 21 mutations, of which 9 are found on the Spike protein. This variant has also spread very rapidly throughout South Africa and beyond its borders. It’s characterized by the presence of the N501Y mutation, from which it takes its name and which is also found in the UK variant. This mutation, along with others, provides the viral strain high transmissibility but doesn’t lead to an increase in symptom severity or lethality of the Coronavirus, while also displaying a higher viral load.

Brazil variant

It’s referred to as variant B.1.1.28 and was first identified in the Manaus region of Brazil. It’s characterized by 12 mutations concentrated on the region encoding the Spike protein. From Brazil, it spread rapidly, specifically to the United States and Japan, where it was identified on January 6, 2021. It’s also known because it was found in a 45-year-old woman who became ill with COVID-19 again after recovering from infection with another strain of SARS-CoV-2 5 months earlier. It has many mutations in common with the South African variant, although the two variants are believed to have evolved independently.

Can variants reduce the reliability of molecular testing?

To date, there’s no evidence that molecular testing, or molecular swabbing, is less effective in detecting infection with SARS-CoV-2 variants. However, researchers are very careful and are working to improve the reliability of molecular tests by developing new tests, called “multiplex”, whereby different probes identify variants. The limitation, of course, is that such tests can only identify known variants and not new variants, for which the best solution is genomic sequencing; as explained briefly in the following section.

Can variants reduce the efficacy of vaccines?

To date, there’s no evidence that the UK, South Africa, and Brazil variants reduce the efficacy of Pfizer-BioNTech and Moderna’s COVID-19 vaccines. However, there are strong suspicions that the South Africa variant reduces the efficacy of the AstraZeneca vaccine on mild-to-moderate cases of infection. The data are still preliminary, as they are based on observations made on a small sampling of people and with an average age of 31; far from the most sensitive target population, namely those over-65.

In any case, attention is high on the part of both the World Health Organization (WHO) and various National Health Systems. During the vaccination campaign, it will be very important to monitor the presence of SARS-CoV-2 variants through an active surveillance system that is already at work in most countries. The aim will be to verify whether these variants will negatively influence the efficacy of the vaccines. The safest strategy involves sequencing the entire Coronavirus genome of a statistically significant number of infected people, in order to identify new variants and also monitor the spread of both old and new variants across a specific country. With this information, public health authorities and pharmaceutical companies will be able to respond quickly and, if necessary, develop new vaccines; particularly those that rely on mRNA that are certainly more flexible than traditional vaccines that use retroviruses.

This post is also available in: Italiano


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