Scientists in Brazil recently reported that two people were simultaneously infected with two different variants of SARS-CoV-2, the virus that causes COVID-19.
This co-infection appeared to have no effect on the severity of the patient’s disease, and both recovered without hospitalization.
While this is one of the few cases registered with SARS-CoV-2 – and the study has yet to be published in a scientific journal – scientists have observed multi-strain infections with other respiratory viruses, such as influenza.
This has raised questions about how these viruses could interact in an infected person, and what this could mean for the generation of new variants.
Viruses are masters of evolution, they constantly mutate and create new variants with each replication cycle. Selective pressures in the host, such as our immune response, also drive these adaptations.
Most of these mutations have no significant effect on the virus. But those who give the virus a benefit – for example, through the ability to replicate or evade the immune system – are cause for concern and should be monitored closely.
The occurrence of these mutations is due to the error-prone replication equipment that viruses use. RNA viruses, such as influenza and hepatitis C, generate a relatively large number of errors each time they replicate. This creates a “quasi-species” of the virus population, rather like a swarm of viruses, each with related but non-identical sequences.
Interactions with the host cells and the immune system determine the relative frequencies of the individual variants, and these coexisting variants can affect how the disease progresses or how well treatments work.
Compared to other RNA viruses, coronaviruses have slower mutation rates. This is because they are equipped with a proofreading mechanism that can correct some of the errors that occur during replication.
Still, there is evidence of viral genetic diversity in patients infected with SARS-CoV-2.
The detection of multiple variants in a subject can be the result of co-infection by the different variants, or the generation of mutations in the patient after the initial infection.
One way to distinguish these two scenarios is to compare the sequences of the variants circulating in the population with those in the patient.
In the above Brazilian study, the identified variants corresponded to different lineages previously detected in the population, indicating co-infection by the two variants.
Get everything mixed up
This co-infection has raised concerns that SARS-CoV-2 might acquire new mutations even more quickly.
This is because coronaviruses can also undergo major changes in their genetic sequence through a process called recombination. When two viruses infect the same cell, they can exchange large parts of their genomes and create completely new sequences.
This is a known phenomenon in RNA viruses. New variants of influenza are generated by a similar mechanism called “reassortment”. The genome of the influenza virus, unlike the coronavirus, comprises eight segments or strands of RNA.
When two viruses infect the same cell, these segments mix to produce viruses with a new combination of genes. Interestingly, pigs can be infected with different strains of influenza viruses, and are referred to as “mixing vessels” that shake them into new strains. The 2009 pandemic H1N1 virus emerged from a rearrangement of one human, avian and two swine flu viruses.
In coronaviruses, which contain only one strand of RNA in each virus particle, recombination can only occur between RNA strands derived from one or more viruses in the same cell.
Evidence of recombination has been found both in the laboratory and in a patient infected with SARS-CoV-2, suggesting that it could stimulate the generation of new variants. In fact, it is proposed that the ability of SARS-CoV-2 to infect human cells has evolved through recombination of the spike protein between closely related animal coronaviruses.
It is important to note that this requires the two viruses to infect the same cell. Even if a person is infected with different variants, they will not interact with each other if they replicate in different parts of the body.
Indeed, this was seen in patients, where different quasi-types of coronaviruses were found in the upper and lower respiratory tract, suggesting that viruses did not directly intermingle at these locations.
The evidence so far does not suggest that infection with more than one variant leads to more serious disease. And while possible, very few cases of co-infection have been reported.
More than 90 percent of infections in the UK currently come from B117 – the so-called Kent variety. With such a high prevalence of one variant in the population, co-infections are unlikely to occur.
By monitoring this landscape, scientists can track the emergence of these new worrisome variants and understand and respond to any changes in their transmission or vaccine effectiveness.
Maitreyi Shivkumar, Associate Professor of Molecular Biology, De Montfort University.
This article has been republished from The Conversation under a Creative Commons license. Read the original article.