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 appears to have no effect on the severity of the patient’s illness, and both have recovered without being admitted to hospital.
Although this is one of the few such cases recorded with SARS-CoV-2 – and the study is yet to be published in a scientific journal – scientists have observed infections with multiple strains with other respiratory viruses, such as influenza.
This has raised questions about how these viruses can interact in an infected person, and what it can mean to generate new variants.
Viruses are masters of evolution, constantly changing and creating new variants with each cycle of replication. Selective pressure in the host, such as our immune response, also drives these adjustments.
Most of these mutations will not significantly affect the virus. But those who benefit from the virus – for example through the ability to replicate or evade the immune system – are concerned and need to be closely monitored.
The occurrence of these mutations is due to the faulty replication machinery that viruses use. RNA viruses, such as influenza and hepatitis C, generate a relatively large number of errors each time they recur. This creates a “quasi-species” of the virus population, rather than a swarm of viruses, each with related but non-identical sequences.
Interactions with the host cells and immune system determine the relative frequencies of the individual variants, and these variants that co-exist can influence how the disease progresses or how well treatments work.
Compared to other RNA viruses, coronaviruses have lower mutation rates. This is because they are equipped with a proofreading mechanism that can correct some of the errors that occur during replication.
There is still 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 emergence of mutations within the patient after the initial infection.
One way to distinguish these two scenarios is by comparing the ranges of the variants circulating in the population with those in the patient.
In the Brazilian study mentioned above, the identified variants corresponded to different descendants previously detected in the population, implying that the two variants have co-infection.
Mix it all together
This co-infection has raised concerns that SARS-CoV-2 is acquiring new mutations even faster.
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 swap large parts of their genomes with each other and create completely new sequences.
This is a known phenomenon in RNA viruses. New variants of influenza are generated by a similar mechanism called ‘re-assortment’. The genome of influenza virus, unlike coronavirus, consists of eight segments or strands of RNA.
When two viruses infect the same cell, these segments mix and produce viruses with a new combination of genes. Interestingly, pigs can be infected with different strains of influenza viruses, referred to as ‘mixing vessels’ that move them into new strains. The 2009 H1N1 pandemic virus originated from a recollection of a human, bird and two swine flu viruses.
With coronaviruses, which contain only one RNA strand in each virus particle, recombination can only take place between RNA strands derived from one or more viruses in the same cell.
Evidence of recombination was found in the laboratory and in a patient infected with SARS-CoV-2, suggesting that it may induce the generation of new variants. In fact, it is suggested that the ability of SARS-CoV-2 to infect human cells has evolved through recombination of the vein protein between closely related coronaviruses of animals.
It is important to note that the two viruses must infect the same cell. Even if someone is infected with different variants, they will not interact with each other if they are repeated in different parts of the body.
It has indeed been seen in patients, where different types of coronaviruses have been found in the upper and lower airways, indicating that viruses in these sites do not mix directly with each other.
The evidence so far does not suggest that infection with more than one variant leads to worse diseases. And although this is possible, very few cases of co-infection have been reported.
More than 90 per cent of infections in the UK are currently caused by B117 – the so-called Kent variant. With such a high prevalence of one variant in the population, there are probably no co-infections.
Monitoring this landscape allows scientists to detect the emergence of these new variants, and to understand and respond to any changes in their transmission or vaccine efficacy.
Maitreyi Shivkumar, senior lecturer in molecular biology, De Montfort University.
This article was published from The Conversation under a Creative Commons license. Read the original article.