SARS-CoV-2 Mutations: All in one place

Why and how do viruses mutate?

All organisms , including viruses, contain genomes that represent their genetic heritage. Viral genomes can be made from either deoxyribonucleic acid (DNA) or ribonucleic acid (RNA). The structure of viral DNA constantly evolves through mutations and with time, new variants are bound to appear. Mutations that happen in viral genomes include substitutions, additions, and deletions and can be the result of accidental errors in DNA replication or errors caused by chemicals or radiation. Many mutations in viral genomes can go unnoticed – the changes are minute and do not result in significant changes in the function of the virus and the immune response of our bodies. Mutations can also cause changes that can hurt a virus and cause its death. Mutations such as these are not inherited and strains of viruses with such mutations do not survive for a significant amount of time.

Mutations represent a danger because of their potential effects on the progress of a disease, its treatment, and vaccine efficacy. The question of whether these new variants carry these hidden dangers naturally poses itself.

The mutation rate of an organism is defined as the frequency of new mutations in a single gene or organism over time. The mutation rate is defined by multiple aspects, including the accuracy of DNA polymerase, the cellular microenvironment, mechanism of replication, correction, and the activity of postreplication repair. Results show that RNA viruses mutate faster than DNA viruses due to RNA being single-stranded. The virus that causes COVID-19 is a single-stranded RNA virus that simply excels at mutating.

SARS-CoV-2 and its mutations

Keeping track of genetic changes of viruses can help us understand how mutations can affect their spread rate and pathogenicity. Since the first appearance of SARS-CoV-2 various mutations has been isolated. Currently, 3 variants are being heavily researched – B. 1.1.7., B 1.351, and P.1. Mutations represent a danger because of their potential effects on the progress of a disease, its treatment, and vaccine efficacy. The question of whether these new variants carry these hidden dangers naturally poses itself.

Variant B.1.1.7

In the United Kingdom, a new variant of SARS-CoV-2 known as 20I/501Y.V1, VOC 202012/01, or B.1.1.7 was detected in September of 2020. This variant has a mutation in the receptor-binding domain (RBP) of the spike protein. The mutation is located at the amino acid position 501 where asparagine (N) is replaced with tyrosine (Y) – N501Y mutation. This mutation increases the strength of the bond between the spike protein and ACE2 receptors.

Another significant mutation, deletion 69-70del, can lead to the loss of 2 amino acids in the spike protein. This mutation, alongside mutation D796H, was found in the blood of a patient that received the plasma of 2 recovered patients as a treatment but died despite this. This variant proved to be more resistant to the plasma of recovered patients than other variants.

The third mutation, P681H, is also of note because it changes the position at which the spike protein is cleaved before entering human cells. Animal tests can help show the effect of this but they cannot give perfect results. Hamsters are not ideal test animals due to how quickly they transmit the virus. Skunks have proved to be much better models but are still far from ideal.

Variant B.1.351

A new variant has appeared in South Africa known as  20H / 501Y.V2 or B.1.351. It has appeared independently of variant B.1.1.7. but shares some mutations with that variant. This variant binds to ACE2 receptors almost 5 times as strong as the most widespread variant commonly referred to just as SARS-CoV-2. It contains multiple mutations of the spike protein, including  K417N, E484K, and N501Y. In contrast to B.1.1.7. it contains no deletion 69-70del. Currently, no evidence points to this variant causing any different symptoms other than normal. The E484K mutation does not characterise this specific variant but also appears in multiple other mutations. It is called an “escape mutation” because it allows the virus to dodge the body’s immune response

The possibility that this variant could cause reinfection among patients who have already battled the disease and survived is proving to be an increasing worry. In the same manner B.1.1.7. variants with the E484K mutation can also cause reinfections. Studies have shown that some mutations can allow the virus to bypass monoclonal antibodies and negate the effects of vaccines. Recent clinical trials conducted by Novavax and Johnson & Johnson have shown that their vaccines are less effective against the South African variant than against the British one, most likely due to a high occurrence of the E484K mutation. Despite this, Novavax reports that its vaccine is still 60% effective which is actually rather good. 

Variant P.1

Variant SARS-CoV-2 known as P.1. first appeared in Brazil. It was identified for the first time in four passengers from Brazil who were routinely tested in airport Haneda outide of Tokyo in Japan. This variant has 17 unique mutations, including three RBD spike-proteins: K417T, E484K, and N501Y. There is evidence that refers to the fact that some mutations in this variant can affect its transmission rate and its antigen profile. The stated mutations can affect the ability of the previously generated antibodies from natural infections or antibodies generated from vaccines to recognize and neutralize the virus. 

A recent study has informed of the case group in Manaus where the variant P.1 was identified in 42% of samples until the end of December. It is estimated that around 75% of the population in this region has been infected by SARS-CoV-2 since October 2020. Nevertheless, the increase in cases since the middle of December has been recorded. The appearance of this variant causes worry because of the potential increase in transmittance or the tendency for reinfection.

How fast can we adjust vaccines to the new variants?

In 2020 science has proved how fast it can progress. Because of that, the change in genetic code which is used in mRNA and the vector-based vaccines or the production of the new vaccine with the inactivated virus could be just as fast. By far the biggest loss of the time and money for the development of the new vaccines against the COVID-19 are big clinical trials. Is it necessary to repeat those tests for every newly updated vaccine? According to the U.S. Food and Drug Administration, no. Although there would not be the need for big clinical trials, there would be a number of smaller clinical trials to ensure the vaccines are immunogenic against the new variants. For comparison, vaccines for the flu are updated every year to make sure they are up to date with the flu virus that is ever more susceptible to change, and those vaccines are quick to be approved. 

All the things we did to prevent the spread of the virus until now will help to limit the spread of the new variants. That includes keeping social distance, wearing a mask, washing hands, and other examples of responsible behaviour during the pandemic. 

According to previous research, Pfizer-BioNTech and Moderna vaccines are effective against all three variants. The AstraZeneca vaccine is effective against the UK and Brazil variants, but at least one study suggests that it has a small effect on the South African variant. The AstraZeneca team has announced they are planning on updating their vaccines so they can be more effective against mutations and that they could be available until autumn. It is possible it will come as a one-dose booster that is updated and introduced every year. The Johnson & Johnson vaccine is effective against all three variants, but less so against the Brazilian and South African variants. The Novavax vaccine is effective against the UK and South African variants. It is still unknown whether the Russian Sputnik V or the CanSino Biologics or Sinovac Biotech Chinese vaccines are effective against these variants.

What do we do?

The increase in the number of cases will put even greater pressure on the health system and can potentially lead to more death cases. Public healthcare officials are studying these variants to learn more about controlling their spread. They want to know whether the variants are more easily transmitted, whether they cause milder or more severe symptoms, can they be discovered using available tests, do they react the same to drugs that are currently used for treating COVID-19, and do they reduce the efficiency of the vaccines. 

The virus SARS-CoV-2 mutates once or twice per month on average. The sum of those mutations is actually far lower than mutations for other viruses, including the flu virus. The more the virus circulates among people, the more possibilities it has to change. Therefore, all the things we did to prevent the spread of the virus until now will help to limit the spread of the new variants. That includes keeping social distance, wearing a mask, washing hands, and other examples of responsible behaviour during the pandemic. 

Translated by: Luka Nalo