SARS-CoV-2—A Virus of Many Mutations

In terms of memorable years and biological disasters, 2020 truly tops the list--witnessing the onslaught of a pandemic, caused by the Novel Coronavirus (SARS-CoV-2), which caused what is now known to be a respiratory illness with mild to severe symptoms: COVID-19. Medical professionals and researchers all over the world faced the challenge of combating a virus and disease that they had little knowledge about. Healthcare workers and essential workers continued to serve at the forefront while others were advised to stay home as much as possible. For nearly the past two years, social distancing and masks have become a part of everyday life. Laboratories have been engaged in a head-to-head race to produce vaccines that can potentially protect citizens against this virus and control the enormous impact of the pandemic.

Now, over a year later, the contrast from where we stood in 2020 is unmistakable and encouraging. Today, we are well aware of the various symptoms of COVID-19 and the recommended ways to protect ourselves from the illness. Doctors and scientists everywhere are armed with more information about the virus and the various methods to treat infected patients. As the pandemic rages on, the world has seen several vaccines gain emergency approval for usage, and administered to hundreds of millions of people around the globe. Vaccines are the safest, most reliable way to make people immune to disease and end a pandemic. However, the novel coronavirus continues to mutate and change every day, threatening the effectiveness of the vaccines and treatments currently in use.

Mutations in SARS-CoV-2

Mutations in viruses are essentially changes in their genetic (DNA or RNA) patterns that occur randomly during replication and are a very commonly observed phenomenon. Mutations occur in organisms more often than we think, but most of them do not lead to any drastic phenotypic changes. At times, mutations can be extremely harmful to an individual. However, every now and then, a mutation will occur that causes the organism to change in such a way that it increases its chances of survival in the ever-evolving world around it. So, a mutation can also be regarded as a mechanism for survival. The world of microorganisms grows and evolves at alarming rates. In proportion to advances in medicine, the speed at which viruses have learned to mutate for their survival has increased exponentially.

Image Courtesy: OSF Healthcare

When the novel coronavirus mutates, a new ‘variant’ is born. This variant may be weaker, stronger, or no different than the previously existing form, with respect to a particular attribute at a time. Over years of research, the medical world has learned, to some extent, to handle and protect individuals against the spread of a disease caused by viruses that mutate and change often. However, the novel coronavirus poses a special challenge because of the speed at which it changes and spreads. This is especially worrying since widespread immunity to the disease has not yet been achieved anywhere in the world. The SARS-CoV-2 virus has been evolving since the beginning of the pandemic and it will continue to do so, to combat the mechanisms we develop against it. In India alone, about 7,000 SARS-CoV-2 variants underwent over 24,000 mutations over the last year.

Variants of the Novel Coronavirus

Most mutations turn out to be useless to the virus with respect to its survival and sustainability in the environment. Nevertheless, over time—either by the accumulation of several mutations or by a sudden chance mutation—a change that contributes to improvement in infection will be brought about in the properties of the virus. This contribution may be in the form of better transmissibility between hosts, better resistance to existing medications, stronger attacks on the immune systems of hosts, and so on, or a combination of such traits. Mutations indirectly bring about such changes by affecting the viral structure. In the case of the novel coronavirus, several new variants with mainly increased transmissibility between hosts have been detected in various regions, because of mutations that enable the virus to bind to our cells more efficiently. This was possible due to changes in the spike proteins, the characteristic protrusions on the surface of all coronaviruses that latch onto cell membranes to allow viral membranes to merge with them.

The CDC classifies all major variants of the novel coronavirus under three categories, from least to most potentially dangerous:

• Variant of Interest
• Variant of Concern
• Variant of High Consequence

Variants of Interest are flagged as such because their appearance has caused significantly large outbreaks in different regions due to various reasons that are said to increase their infectivity, transmissibility, or resistance to antibodies and treatments. Their structures can be studied in detail to learn more about the way the virus has changed and how a specific change was brought about genetically. Variants of interest at present, as listed by the CDC, are the B.1.525 (United Kingdom/Nigeria), B.1.526 (United States), B.1.526.1 (United States), B.1.617 (India), B.1.617.1 (India), B.1.617.2 (India), B.1.617.3 (India), and P.2 (Brazil) variants.

A Variant of Concern is one for which enough evidence can be presented regarding its increased transmissibility, reduced neutralization by vaccines, treatments and antibodies generated from the previous infection, and greater severity of disease caused leading to more hospitalizations and deaths. Such variants currently being monitored are the B.1.1.7 (United Kingdom), B.1.351 (South Africa), B.1.427 (United States), B.1.429 (United States), and P.1 (Japan/Brazil) variants.

All of these variants share a specific mutation in the spike protein called the D614G mutation, which seems to have brought about a quicker spread of these types compared to forms without this change.

A Variant of High Consequence is one for which currently existing preventive Measures and Medical Countermeasures (MCMs) have drastically reduced effectiveness compared to those for other variants. At present, no variant of the SARS-CoV-2 virus has been listed under this category.

Major Variants in India

During the beginning of the pandemic, a strain of the novel coronavirus consisting of a small number of variants, all behaving almost the same way, circulated across India. This strain was responsible for the first wave of infections in the country. Later on, three significant variants of concern that arose around the world, namely the B.1.1.7 (United Kingdom), B.1.351 (South Africa), and P.1 (Brazil) variants gained entry into the nation, and this led to a rise in cases. The B.1.36 variant, carrying the N440K mutation and specific to India, based on limited data, may have caused a surge in cases in Bengaluru, and the mutation found in it was also found in other forms of the virus infecting southern states.

Possibly the most notable variant that originated in India and has so far spread to about forty countries, beginning from the state of Maharashtra, is the B.1.617 variant, rumoured to have been the main reason behind an especially devastating second wave of infections in India. Among other changes, this variant exhibits two concerning mutations, called E484Q and L452R, which alter the spike protein structure such that the virus can bind more easily to cell membranes. This change is believed to have caused an increase in transmissibility. The L452R mutation is also responsible for conferring the property of ‘immune escape’ to the virus, which makes it easier for it to evade antibodies generated by previous infection, those generated by vaccine doses, and other forms of immunity that do not make use of antibodies. This strain, including subtypes of the B.1.617 variant like the B.1.617.2 form, seems to have overtaken other strains to presently become the dominant form of the virus in the country.

Variants and Vaccines

The B.1.617 variant and its subtypes with worrisome mutations do present some threats to the effectiveness of the ongoing vaccination drive in the country. Research by experts shows that this strain does have increased potential to cause disease—however, the data collected so far is limited and cannot be reliably extrapolated to humans to predict virus behaviour. Two small studies conducted to test Covaxin made by Bharat Biotech and Covishield by the Serum Institute of India showed that these vaccines are still useful against the newly dominant strain, but with some reduced effectiveness of neutralizing antibodies generated by the Covaxin vaccine. Some healthcare workers in Delhi who were vaccinated with Covishield did, however, get reinfected with the B.1.617 strain.

A test conducted on blood serum obtained from nine individuals vaccinated with one dose of the Pfizer vaccine shows that the neutralizing antibodies generated were 80% less potent against some mutations in this strain. Serum collected from those who had received two doses of the Pfizer vaccine contained antibodies that were about 67% less potent. Other research that tested serum collected from 15 individuals who had previously been infected with the virus provided the conclusion that the generated antibodies were only about 50% potent against the new strain.

A detailed table with details on variants recognized thus far. Image Courtesy: India Today.

However, this does not imply that the vaccines are ineffective, as these conclusions were drawn from limited samples. Furthermore, experts regard serum testing as a slightly unreliable guide, since the number of antibodies generated by a vaccine may be much larger and immunity from other cells like the T-cells of the immune system is not taken into account. An example is immunity provided by vaccines against the B.1.351 variant. Studies using small samples predicted that current vaccines would be seemingly less effective in their neutralizing action against B.1.351, but the data available from the real world proved that this was not the case and that these vaccines still remained useful for preventing severe disease.

It is safe to say that current and future vaccines still remain our best bet for the protection and preservation of public health. Though it is tough to accurately predict the way a virus will change in the future, the development of new vaccines with changes in their compositions in accordance with major mutations of the novel coronavirus is possible. Severe mutations in the viral structure can also be prevented by individuals helping to prevent the spread of the virus by following precautions. A vigorous and quick vaccination drive to provide immunity to the majority of the country’s population, as all of us continue to maximize our stay indoors, seems to be the quickest, safest way to control the pandemic, to ensure that the ones worst affected receive the available treatment, and to tame this disease that has taken over the world.