Ever since COVID-19 was declared a pandemic back in March, our hopes of a return to normality have been pinned on the discovery of a vaccine against SARS-CoV-2. Positive results have now been reported from Phase 3 vaccine trials by Moderna, Pfizer and AstraZeneca, with the recent approval and distribution of Pfizer’s vaccine in the UK potentially signalling the beginning of the end of the pandemic. However, a potential stumbling block has been highlighted in recent weeks. In Denmark, over 17 million mink had to be culled after mutated SARS-CoV-2 strains were discovered in the animals, with these new variants then going on to infect 214 humans. Denmark is no outlier either – evidence of infection has also been found on mink farms in Italy, Sweden, the Netherlands, and the United States. Having already crossed the species barrier into humans, could COVID-19 jump back into animals before returning to humans in a new form to prolong the pandemic?

Anxiety over a new SARS-CoV-2 strain arises due to the potential of a mutation to alter the viral structure, especially in the spike protein, which is the region of the virus that binds to human cells allowing entry and infection. This could give a new strain the ability to evade a person’s immunological memory, from either a previous infection or vaccine. A mutated virus may also be more severe or transmissible than previous strains.

“Mutations are only noticed when they ‘go wrong’ and produce a more virulent strain, and never during the countless occurrences when they are harmless.”

How could these outcomes occur? Let’s look first at what happens when a virus “jumps” across the species barrier – otherwise known as a zoonosis. When a virus usually dominant in one species enters a member of another and causes an infection, it will begin to replicate in the new host. Mutations will accumulate randomly during replication in the new virus population, and mutations suited to the new host will be positively selected for. As a result, viruses with these more “suitable” variants will replicate more – a process known as antigenic drift. This means the virus becomes more suited for its new zoological environment.

An example of this process can be seen in influenza, where two distinct variants of RNA-dependent RNA polymerase (a viral enzyme needed for replication) have developed – one particularly suited to birds and one to humans – due to exposure of the virus to a new host species. In the case of COVID-19, one positive is that SARS-CoV-2 is relatively stable and does not mutate as quickly as other viral genomes – it encodes a proof-reading enzyme, known as nsp14, which can correct errors in RNA replication when new viruses are produced. This means it is highly unlikely that a new COVID outbreak will arise each year (unlike the flu) but it doesn’t mean we’re safe from new strains, as seen in the latest evidence from Denmark.

Whether a mutated virus will evade a vaccine depends on its structure. Often mutations in viruses cause such minute changes to the structure that vaccines developed against the original virus will still work. However, we have seen that this is not always the case – one particular SARS-CoV-2 variant from Danish mink, known as “Cluster 5”, has four different mutations in the spike protein. This is problematic for vaccine development because the spike protein is on the outer surface of the virus, so it tends to be the region against which antibodies are produced. This means spike protein modifications could potentially lead to a loss of immunity from COVID-19.

“We don’t know whether it’s possible for a mutated SARS-CoV-2 to evade current vaccine candidates at the moment.”

Alternatively, there is every chance that a variant that develops in an animal will then be so significantly different that the strain will be ineffective at infecting or causing disease in humans. A virus with this kind of mutation would fizzle out quickly unless it could re-adapt to the human environment. In a way, this perpetuates public fear over mutated viruses – mutations are only noticed when they “go wrong” and produce a more virulent strain, and never during the countless occurrences when they are harmless.

The chance of this episode being a one-off event, perhaps due to an unfortunate but rare interaction between an infected human and susceptible animals, is unknown. What we do know is that mink are far from being the only potential animal hosts of SARS-CoV-2 – other animals such as ferrets, cats, hamsters and bats have also been shown to harbour infection. As several of these possible hosts can be domesticated by humans, some suggest the increased contact between pets and their owners could give rise to more infections in these animals, increasing the chances of mutation. However, the evidence for this is sketchy at best, indicating pets are not a risk for coronavirus transmission. This is a relief for those concerned about new mutations from animals spilling over into humans, but with the current risk of human-to-animal transmission and the history of animal origin for new coronaviruses, we can never be sure.

What does this mean for the success of a vaccine against COVID-19? We don’t know whether it’s possible for a mutated SARS-CoV-2 to evade current vaccine candidates at the moment, but if we suppose that it could, these candidates will almost certainly have to be modified. Two of the leading candidates (from Pfizer/BioNTech and Moderna) use novel messenger RNA (mRNA) technology, where a sequence coding for the spike protein is injected into a person, giving cells the template to produce the spike, resulting in an immune memory in the vaccinated individual. As the mRNA sequence in these vaccines is based on the viral genome, the sequence could theoretically be changed to target a new strain, but these new vaccines would have to be tested for safety and efficacy, and mass-produced all over again.

SARS-CoV-2 is just like any other virus – it mutates constantly. We don’t know if this will cause it to become more dangerous or evade humanity’s attempt at stopping the virus. Our only option is to constantly monitor its presence in animals and analyse any new variants that are produced.