Several researchers have proposed that there is more than one strain since the emergence of the new coronavirus, called SARS-CoV-2, and that mutations have led to changes in how infectious and deadly it is. Opinions, however, are divided.
Genetic variations are an everyday and natural phenomenon. Each time genetic material is copied, they can happen.
If a virus replicates inside the cell it has infected, there may be minor variations in the myriad of new copies inside. Why does it matter?
When mutations result in chnages in how a virus operates, they can have major consequences. These do not necessarily have to be detrimental to the host, but mutations may weaken those interactions in the case of vaccines or drugs that target specified viral proteins.
Several scientific studies have illustrated changes in the genetic code of the virus since the appearance of SARS-CoV-. This has sparked debate on whether or not there are many strains, whether that has an effect on how quickly a host can be infected by the virus, and whether or not it affects how many more people will possibly die.
Most scientists have expressed caution. They review what researchers already know about SARS-CoV-2 mutations in this Special Feature and hear from experts about their opinions on what these mean for the pandemic.
Why are mutations significant?
SARS-CoV-2 is an enveloped RNA virus that encodes its genetic material in single-stranded RNA. It is making its own replication machinery inside a host cell.
RNA viruses have extraordinarily high levels of mutations and their enzymes in replication are vulnerable to errors when producing new copies of viruses.
Virologist Prof. Jonathan Stoye, a senior group leader at London’s Francis Crick Institute in the United Kingdom, told MedicalNewsToday what makes mutations in virus significant.
“A mutation is a change in a genetic sequence,” he said. “The fact of a mutational change is not of primary importance, but the functional consequences are.”
When a specific genetic modification alters the target of a drug or antibody that works against the virus, then all viral particles with the mutation will outgrow those that don’t.
“Changing a protein to allow virus entry into a cell that carries very small amounts of receptor protein may also give the virus a growth advantage,” Prof. Stoye added.
“It should be stressed, however, that only a fraction [of] all mutations will be beneficial; most will be neutral or harmful to the virus, and will not persist.”
“Mutations in viruses clearly do matter, as evidenced by the need to prepare new vaccines against [the] influenza virus every year for the effective prevention of seasonal flu and the need to treat HIV-1 simultaneously with several drugs to [prevent the] emergence of resistant virus.”
– Prof. Jonathan Stoye
Researchers find mutations
A research study by a team from Arizona State University in Tempe has recently been featured in MNT. The paper described a mutation mimicking a similar occurrence that occurred during the 2003 SARS epidemic.
The team analyzed five samples of nasal swab, which had a positive test result for SARS-CoV-2. They found that one of these had a deletion which indicates that there was a missing portion of the viral genome. 81 nucleotides have vanished in the viral genetic code, to be exact.
Past studies revealed that similar mutations reduced the replicability of the SARS virus.
Another research, this time in the Journal of Translational Medicine, indicated that similar mutation patterns were picked up by SARS-CoV-2 in various geographic regions.
The researchers, from Baltimore University of Maryland and Ulisse Biomed, Italian biotech company in Trieste, studied eight recurrent mutations in 220 COVID-19 patient samples.
Three of these were found exclusively in European samples, and three more exclusively in North American samples.
Another research, which has not been through the peer review process yet, indicates that in some cases, mutations from SARS-CoV-2 have made the virus more transmissible.
In the paper, Bette Korber — from New Mexico’s Los Alamos National Laboratory — and collaborators describe 13 mutations within the viral genome region that encodes the spike protein.
This protein is essential to infection, as it helps to bind the virus to the host cell.
The researchers note that one particular mutation, which changes an amino acid in the spike protein, “may have originated either in China or Europe, but it [began] to spread rapidly first in Europe, and then in other parts of the world, and is now the dominant pandemic type in many countries.”
The results of this study, Prof. Stoye commented, are not surprising in some ways.
“Typically, the viruses are finely tuned to the host species. If they jump species, for example from bat to human, a degree of retuning is inevitable both for avoiding natural host defenses and for optimum interaction with the new host ‘s cells, “he said.
“There will be random mutations and most suitable viruses will predominate,” he said. “Therefore it does not seem surprising that SARS-CoV-2 is evolving after its jump to the human population and spread through it. Clearly, these improvements are taking place at the moment, as demonstrated by Korber [and his colleagues]’ obvious spread of the [mutation].”
However, at this point Prof. Stoye does not think it is clear how mutations can influence SARS-CoV-2 ‘s actions in the long term.
“Fears about the evolution of SARS-CoV-2 to resist the vaccines and drugs still in development are not unreasonable,” he explained. “However, we can also see the transition of a less dangerous form of the virus, as the so-called seasonal coronaviruses might well have arisen after initial human colonization.”
Opinions remain divided
Earlier this year, researchers at Beijing University in Beijing , China, published a paper in the National Science Review identifying two distinct SARS-CoV-2 lineages, which they called “S” and “L.”
They analyzed 103 samples of the virus sequence, and wrote about 70 percent of the L lineage.
Nonetheless, a team at the University of Glasgow ‘s Institute for Virus Research in the UK. Disagreed with the findings, and published their data criticism in the Virus Evolution journal.
“In view of the implications of these statements and the extensive media attention of these types of publications, we have reviewed the data submitted in depth […] and found that the main conclusions of that paper can not be substantiated,” the authors write.
The team was composed of Prof. David Robertson, head of Viral Genomics and Bioinformatics at the Virus Research Centre. Nccmed questioned his thoughts on the probability of more than one SARS-CoV-2 strain being present.
“We can’t say that there are new strains of the virus until there is some evidence of a change in virus biology. It’s important to appreciate that mutations are a normal byproduct of virus replication and that most mutations we observe won’t have any impact on virus biology or function,” he said.
“All reports of, for example, shifts in amino acids in the spike protein are significant, but these are at best a hypothesis at the moment. There are currently a variety of labs checking their possible effects.
Prof. Stoye claims that, at the moment, it is “more a matter of semantics than anything else.”
“We have different strains because we do have different sequences. It only makes sense to reclassify the different isolates when we have a better understanding of the functional implications of the observed evolutionary changes, “he said.
“We can try to correlate the sequence variation with the prognostic or therapeutic implications at that point. That can take several years.
Serotypes and future research
So, what kind of evidence are skeptical scientists looking for in the debate over multiple strains of SARS-CoV-2?
Prof. Mark Hibberd of the London School of Hygiene and Tropical Medicine in the UK was asked by Nccmed to weigh in on the debate.
“For virologists, ‘strain’ is more of a subjective word that doesn’t always have a specific meaning,” he said.
“The concept of ‘serotype,’ which is used to classify strains that can be differentiated by the human immune response, may be more useful in the SARS-CoV-2 situation — an immune response to one serotype usually does not defend against another serotype. There is no conclusive evidence for SARS-CoV-2, that this has already happened.
“In order to prove that the virus has modified genetically enough to produce a particular immune response, we will need to characterize the immune immunity and demonstrate that it worked for one serotype and not another,” he added.
Professor Hibberd clarified that scientists are researching antibody neutralization to help them identify a SARS-CoV-2 serotype. These antibodies can prevent a host cell from being infected by the virus but may not be effective against a new strain.
“Several groups around the world have identified a specific mutation in the SARS-CoV-2 spike protein, and they are concerned that this mutation might alter this type of binding, but we cannot be sure it does that at the moment. More likely, this mutation will likely affect the virus binding to its receptor […], which might affect transmissibility.”
– Prof. Mark Hibberd
“Ideally, we need experimental evidence, [such as] a demonstration of a mutation leading to a functional change in the virus in the first instance and, second, a demonstration that this change would have an effect on [people with the infection],” suggested Prof. Robertson.
He pointed to lessons learned by experts during the outbreak of Ebola in West Africa in 2014–2018, where several research groups had suggested that a mutation resulted in the virus becoming easier to pass between people and more deadly.
Experiments in cell culture showed the mutated virus was able to replicate faster. But, as scientists later researched this in animal models, they found that without the mutation, it did not behave differently from stains.
Scientists around the world continue to search for answers to the many unexplained SARS-CoV-2 questions. No doubt, in the coming months and years we’ll see more research emerging that will assess the impact of SARS-CoV-2 mutations on the COVID-19 pandemic and the future of this new coronavirus.
