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 patients’ illness, and both recovered without the need for hospitalization.
Although this is one of the few cases recorded with SARS-CoV-2 – and the study has not yet been published in a scientific journal – scientists have observed infections with various strains of other respiratory viruses, such as influenza.
This raised questions about how these viruses can interact in an infected person and what it could mean for the generation of new variants.
Viruses are masters of evolution, constantly changing and creating new variants with each replication cycle. Selective pressures on the host, like our immune response, also drive these adaptations.
Most of these mutations will not have a significant effect on the virus. But those who give the virus an advantage – for example, by increasing its ability to replicate or evade the immune system – are a cause for concern and need to be monitored closely.
The occurrence of these mutations is due to the error-prone replication machinery 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, like a swarm of viruses, each with related but not identical sequences.
Interactions with host cells and the immune system determine the relative frequencies of individual variants, and these coexisting variants can affect how the disease progresses or how treatments work.
Compared to other RNA viruses, coronaviruses have lower mutation rates. This is because they are equipped with a review 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 person can be the result of co-infection by the different variants or the generation of mutations within the patient after the initial infection.
One way to discriminate between these two scenarios is to compare the sequences of the variants that circulate in the population with those of the patient.
In the Brazilian study mentioned above, the variants identified corresponded to different strains previously detected in the population, implying co-infection by the two variants.
Mixing it all up
This co-infection has raised concerns that SARS-CoV-2 will 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 with each other and create completely new sequences.
This is a known phenomenon in RNA viruses. New variants of the flu are generated by a similar mechanism called “rearrangement”. 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 and match to produce viruses with a new combination of genes. Interestingly, pigs can be infected with different strains of the flu virus and have been called “mixing containers” that turn them into new strains. The 2009 H1N1 pandemic virus arose from a rearrangement of a human, avian and two swine flu virus.
With coronaviruses, which contain only one strand of RNA in each virus particle, recombination can only occur between strands of RNA derived from one or more viruses in the same cell.
Evidence of recombination was found both in the laboratory and in a patient infected with SARS-CoV-2, suggesting that this could lead to the generation of new variants. In fact, the ability of SARS-CoV-2 to infect human cells is proposed to have developed through recombination of the peak protein between closely related animal coronaviruses.
It is important to note that this requires that the two viruses infect the same cell. Even if a person is infected with several variants, if they replicate in different parts of the body, they will not interact with each other.
In fact, this has been observed in patients, where different coronavirus quasi-species have been found in the upper and lower airways, suggesting that the viruses in these locations were not mixing directly.
Evidence so far does not suggest that infection with more than one variant leads to more serious illnesses. And although possible, very few cases of co-infection have been reported.
More than 90 percent of infections in the UK are currently due to B117 – the so-called Kent variant. With such a high prevalence of a variant in the population, co-infections are unlikely to occur.
Still, monitoring this scenario allows scientists to monitor the emergence of these new worrying variants and to understand and respond to any changes in their transmission or vaccine efficacy.
Maitreyi Shivkumar, Senior Professor in Molecular Biology, De Montfort University.
This article was republished from The Conversation under a Creative Commons license. Read the original article.