There have been several recent reports of new “strains” of SARS-CoV-2 arising through mutation that have the potential to increase the severity of the pandemic. However, further analysis has shown these conclusions were premature and there is currently no robust evidence that any of the mutations that have been described have any implications for the spread of COVID-19. Future evolution of the virus may lead to changes that positively or negatively affect human health outcomes and monitoring of viral genetic changes is important.
What is a virus ‘strain’?
When scientists use the word strain, they are referring to a genetically distinct virus lineage, distinguishable by one or more mutations from another strain. Strains may or may not be biologically (functionally) distinguishable from one another and some virologists use the term strain only for the former. Two strains would be biologically different if they elicited different responses from the human immune system, or if they varied in their transmission characteristics.
What are viral mutations?
When a virus infects a cell and begins making copies of itself, it starts by replicating its genetic information, which for the COVID-19 virus is encoded in an RNA molecule. More complex organisms have a variety of “proof-reading” mechanisms to ensure high-fidelity replication; however, these are less developed in RNA viruses where the process is particularly error-prone, leading to a relatively rapid accumulation of mutations over time. SARS-CoV-2 does carry some proof-reading enzymes and its mutation rate is lower than many other RNA viruses, such as influenza virus, norovirus and human immunodeficiency virus (HIV).
Is SARS-CoV-2 mutating into a more aggressive virus?
The majority of mutations that arise during viral replication have very little effect on the virus (termed as “neutral”), with no functional significance for infection. The next most common type of mutation disrupts one or more viral proteins and renders the virus less capable of replication or transmission. Such deleterious mutations do not persist as those viruses are weeded out by natural selection.[1][2] However, mutations could arise that confer an advantage to the virus, for example by allowing the virus to infect humans more readily. A virus with an advantageous mutation might spread more readily between people (higher transmissibility), be less well recognised by the immune system (lower antigenicity), or enable the virus to escape the effects of medications (higher drug resistance). A particular concern is whether a viral strain favoured by natural selection is causing an increased severity of disease (higher pathogenicity).
A SARS-CoV-2 mutation was identified that was thought to have created a more ‘aggressive’ form of the virus, on the basis that viruses carrying this mutation had become more prevalent in the study population.[3] During a pandemic, small numbers of viruses will spread to new areas and create new localised epidemics, which then grow exponentially. This means that any mutations which spread to these new uninfected areas will rapidly increase in frequency, even if the mutations are completely neutral, or even detrimental, to the virus. Subsequent studies[4] showed that the reported observations could be explained by this process and that there was no evidence that a more aggressive form of the virus had arisen by this mutation.[3]
A second study analysed a set of mutations in the spike protein of SARS-CoV-2,[5] and concluded that a specific mutation had increased in frequency as the virus spread from China into Europe, North America, and Australia. The authors concluded that this increase in frequency arose because the mutation had made the virus more transmissible, allowing it to outcompete viruses that did not contain the mutation. However, this conclusion proved controversial, with many scientists arguing that the prevalence of the mutation could have increased by random (stochastic) processes even if it did not increase fitness. Subsequently, a more formal analysis of the frequency of this mutation by another team suggested that it decreased transmissibility.[6] Thus, as it stands, there is no clear evidence that any mutation confers greater transmissibility.
Why is it important to track viral mutations?
Mutations in the virus are being actively monitored by extensive sequencing of viral genomes isolated from patients across the world. This information will allow researchers to track new variants of the virus with unique genome mutations, improve their understanding of virus transmission, and quickly determine whether new mutations are changing the properties of the virus. At present, there is no evidence that any of the mutations that have been observed in SARS-CoV-2 have affected viral transmissibility or the disease in humans. However, future mutations might arise that have negative (or positive) effects on human disease prevalence and health outcomes, and so genetic monitoring and biological characterisation of new mutations is a high research priority. Because of the significance of such findings, careful consideration of the evidence prior to publication is critical.
