Brazzaville – New COVID-19 variants have emerged in Africa as the continent records a new peak in infections. While virus mutations are not unusual, those that are more infectious are worrisome. Professor Francisca Mutapi, Professor in Global Health Infection and Immunity, University of Edinburgh, explains the implications of SARS-CoV-2 variants and what African countries can do to respond.

Why do viruses mutate, and should we be worried about SARS-CoV-2 variants?

Viruses mutate as they replicate. Replication requires that the virus’s genetic information is copied. But this copying is not accurate. It produces mistakes such as substitutions, deletions or sometimes insertions of amino acids – the building blocks of proteins. These changes are called mutations.   

Some of these mutations are advantageous to the virus allowing it to survive in new hosts or new environments. A new environment can mean evading an immune response mounted by the host or a therapeutic drug. The SARS-CoV-2 virus mutates just like other viruses. To date there have been about 4000 mutations in its spike protein alone.

Mutations in viruses are notable only when they change an important characteristic of the virus such as its ability to infect different hosts, rate of transmission, ability to evade the host’s immune system, vaccines, therapeutics and diagnostics, cause pathology or disease severity.

Mutation, variants, lineages and strains are used quite often. What is the difference?

Although mutation, variant and strains can be used interchangeably when describing the SARS-CoV-2 epidemiology, it is important to understand the distinctions. Mutation refers to the actual change in the genetic sequence. Viruses whose genetic sequences differ are called variants. Variants with a few mutations belong to the same lineages. Lineages are important for showing how a virus spreads through communities or populations. Strictly speaking, a variant is a strain when it has a different characteristic.

How many variants are circulating in Africa and what do we know about them?

It is difficult to know the total number of variants circulating in Africa because we do not have systematic sequencing surveillance from all the countries. To date there are just under 5000 publicly available sequences from 24 of the 47 countries in the World Health Organization African (WHO) region. Using these data, we have identified 145 lineages from the region. Of these lineages, the variants causing concern currently are the B.1.351 or the 501Y.V2 that was first identified in South Africa. Outside South Africa, this has been reported in Botswana and Zambia. We await the sequence information of the new variant that has been reported in Nigeria.

What is the implication of the variants on COVID-19 transmission, therapeutics and vaccines?

In terms of transmission, some of the current variants such as B.1.351 or 501Y.V2 originally reported in South Africa have mutations in the spike protein. This protein binds to the human cells to facilitate infection. These variants are believed to increase binding to the receptor on human cells and increase transmission.

In terms of natural immunity or immune-derived therapeutics, mutations in the spike protein of the B.1.351 or 501Y.V2 may, in theory, reduce, but not obliterate the recognition of the virus by antibodies. This is because, in practice, the human immune system will recognize more than a single region of the spike protein. The spike protein is made up of 1273 amino acids and changes in one or a few of its amino acids is not enough to stop recognition of the whole protein.

Currently, most COVID-19 vaccines target the spike protein. There are some vaccines such as inactivated virus vaccines developed in China that target the whole virus. Mutations may reduce vaccine efficacy directed against the spike protein but will not obliterate their effects. As explained, this is because the immune responses they induce target more than a single part of the spike protein. Inactivated vaccines target an even greater array of viral proteins, inducing several protective immune responses. This instils redundancy in the protective immune responses.

To date, there is no indication that mutations recorded in the B.1.351 or 501Y.V2 variant affect the function of drugs.

Does vaccine development take virus mutation into consideration?

Vaccine developers are aware of virus mutations and take this into account. They use several techniques including mathematical models of virus replication to predict the course of mutations and their potential impact on vaccine escape dynamics. This work informs various factors including which strain is selected for use in vaccines and which type of inactivation strategy to use in the case of inactivated virus vaccines.

Can vaccines be restructured to tackle virus mutations that emerge later?

The information that is put in a vaccine about a virus comes from the virus either in the form of genetic information (RNA or DNA) or the whole virus itself. This means that a vaccine can be customized to target specific variants that arise as a result of new mutations. In fact, we already use this approach for the annual influenza vaccines. For the latter, sentinel laboratories around the world use genomic sequence surveillance to identify influenza strains affecting people and twice a year WHO convenes a meeting to review these data and decide on the strains to be used in the next vaccine. Thus, the technology and global governance framework to restructure SARS-CoV-2 vaccines targeting new variants already exists.

What should African countries do to better respond to the new variants?

Unless new variants differ significantly in their mode of transmission or their disease course, current mitigation strategies should work across variants. To strengthen their responses to currently circulating SARS-COV-2 variants, African countries need resources and context-specific approaches to implement currently recommended mitigation strategies for infection prevention and control, and patient clinical management.