Should We Worry About the Coronavirus MUTATING During the Outbreak?

Mutation is a word that itself evokes unexpected and strange changes...

As the novel coronavirus (SARS-CoV-2) spreads these days, as during other viral outbreaks, discussions based on inadequate or incorrect information focus on the concept of mutation. In real life, however, mutations are a natural part of the viral life cycle and rarely change the course of outbreaks dramatically.

The everyday word ‘mutation’ does not fully reflect the complexity of mutation as a concept in evolutionary theory. In science-fiction films, ‘mutating’ means undergoing marked and serious changes, often, for example, acquiring superpowers. In the entertainment and film industries, dramatizing mutation is also a common metaphor used to portray outbreaks more effectively. In the 1971 film ‘The Andromeda Strain’, we see a microbe from space evolving constantly to acquire new biological properties, including new strategies such as breaking down plastic that can overcome methods of containment and transport. In the 1995 thriller ‘Outbreak’, a virus similar to the cause of Ebola today rapidly mutates into a highly infectious form capable of airborne transmission. Given how quickly such fictional stories can reach all sections of society and their appeal to the masses, it is not surprising that, in real-world pandemics, journalists and even scientists may be inclined to benefit from conspiracy theories.

In the context of the current novel coronavirus outbreak, our media and scientific communication channels are overflowing with reports that misrepresent mutation and terrify people. Headlines such as ‘DNA detectives search for dangerous mutations in the new virus’ embed the expectation that the virus will inevitably mutate and become more deadly. Such reports encourage doomsday scenarios that may cause the public health measures that actually bring outbreaks under control to be perceived as invalid and useless.

Unlike in science-fiction films, dramatizing viral mutation is not harmless. To understand how misinterpreting the effects of mutation directly affects our health and safety, we need only look at recent outbreaks. For example, before the Zika virus outbreak that emerged in Central and South America in April 2015, a mutation arose in the membrane region of the viral genome (prM-S139N). Animal experiments subsequently reported that this mutation increased the Zika virus's ability to affect the nervous system (neurovirulence). However, before these findings were definitively established, incorrect reports began to spread that this mutation caused congenital Zika syndrome, particularly its microcephaly component (a skull smaller than it should be). When Zika was detected in India in 2018, the Indian government, influenced by this unproven finding and the absence of the ‘mutation attributed to microcephaly’ in the virus strains there, prepared action plans on the assumption that the virus would not adversely affect fetuses. Yet the situation was not that simple!..

Although it is very rare for every mutation in viral genetic material to become established and for the complex properties of viruses to change completely, mutation features in a substantial proportion of news reports.

In fact, mutation is quite ordinary in the lives of RNA viruses (coronaviruses are also RNA viruses). RNA viruses contain RNA polymerase, an error-prone enzyme (RNA polymerase is the enzyme that copies genetic material). Errors accumulate during each copying cycle. These cycles occur rapidly, within hours, in viruses and are sufficient to generate a diverse enough population of viruses in a single infected patient. Although this capacity for mutation drives evolutionary change, most mutations alter viral functions to the virus's disadvantage. In addition, the route by which viruses pass from person to person (mode of transmission) and their virulence (ability to infect) are usually controlled by multiple genes. Many mutations favorable to the virus therefore need to come together for these properties to change. Despite high mutation rates, it is unusual to encounter viruses that change their mode of transmission on such short evolutionary timescales. Taken together, these considerations show the considerable uncertainty about which traits will be retained through natural selection.

Moreover, the role of natural selection in viral evolution cannot be predicted easily. The evolution of viral virulence is highly complex and has opened the way to extensive research in evolutionary theory. For example, an increase in the rate of viral spread results in greater viral virulence. An increased rate of spread often, though not always, means an increase in the amount of virus released from cells. In this situation, however, a person may become too ill to infect others, thereby actually reducing the virus's rate of spread. This is why predicting changes in virulence is so difficult with our limited knowledge of evolutionary forces and selection dynamics. Of course, this does not mean that mutations and natural selection do not occur during outbreaks. The problem lies in the difficulty of determining their epidemiological consequences. Rigorous experimental and epidemiological studies of viral phenotypes are needed.

Naturally, questions will be asked about whether SARS-CoV-2 will mutate to humans' disadvantage. Consider the SARS-CoV-1 epidemic of 2002-2003. Large deletions in the ORF8 region of the SARS-CoV-1 genome and mutations in genes encoding the S (spike) protein were discovered early in the outbreak. Later, the population (group) of viruses carrying these mutations became dominant in the epidemic. This suggests that the virus had adapted in humans. Based on these observations, it was proposed that the SARS epidemic was partly caused by these changes, but this claim has not been proven. Could SARS-CoV-2 adapt in a similar way? Yes. Will adaptation lead to more deaths? Not very likely.

The receptor-binding region the virus uses to enter human cells is a focus of its mutations because this region is known to be more variable. For example, the binding regions of bat viruses and SARS-Cov-2 are 98% identical. However, the 2% difference has enabled it to acquire the ability to infect humans.

On the other hand, the new virus's attachment protein has an affinity for receptors on human cells that is 10-20 times greater than that of the old virus that caused the outbreak in 2003. The significance of this change is that, although the binding regions of these two viruses are also 98% similar, antibodies elicited by the old virus's binding region are not very effective against the new virus. The 2% difference also causes this. Thus, the new virus's binding region must be used when developing drugs.

It is now time to reshape our understanding of mutation. Mutations do not indicate strange, distant and destructive new viral traits. Instead, they can broaden our understanding of emerging outbreaks. The pattern and temporal course of mutations in viral genomes form the basis of phylogenetic studies. Phylogenetic studies can, in turn, predict the course of outbreaks in real time. For this purpose, the field that constructs phylogenetic trees, ‘genomic epidemiology’, is also being used to control the SARS-CoV-2 pandemic and in its mitigation. Rapid and open global sharing of viral genomes will make research into viral spread possible.

Rather than fearing mutations, we need to accept this reality and study it. After all, mutations are an inevitable consequence of being a virus.

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