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 seemed to have no effect on the severity of the patients’ illness and they both recovered without having to be hospitalized.
Although this is one of the few such cases reported with SARS-CoV-2 – and the study has not yet been published in a scientific journal – scientists have observed infections with multiple strains of other respiratory viruses, such as the flu.
This raised questions about how these viruses can interact with an infected person and what they might mean for the generation of new variants.
Viruses are masters of evolution, constantly moving and creating new variants with each cycle of replication. Selective host pressures, such as our immune response, also determine these adaptations.
Most of these mutations will not have a significant effect on the virus. But those that give the virus an advantage – for example, by increasing its ability to reproduce or bypass the immune system – are a cause for concern and need to be closely monitored.
The occurrence of these mutations is due to the error-prone replication mechanism used by viruses. RNA viruses, such as influenza and hepatitis C, generate a relatively large number of errors each time they reproduce. This creates a “quasi-species” of the virus population, rather like a swarm of viruses, each with related but unidentified sequences.
Interactions with host cells and the immune system determine the relative frequencies of individual variants, and these coexisting variants may affect how the disease progresses or how well the treatments work.
Compared to other RNA viruses, coronaviruses have lower mutation rates. This is because they are equipped with a correction mechanism that can correct some of the errors that occur during replication.
However, there is evidence of viral genetic diversity in SARS-CoV-2 infected patients.
Detection of several variants in a person could be the result of co-infection by different variants or the generation of mutations inside the patient after the initial infection.
One way to discriminate these two scenarios is by comparing the sequences of variants circulating in the population with those in the patient.
In the Brazilian study mentioned above, the identified variants corresponded to different lines that had been previously detected in the population, involving co-infection by the two variants.
Mixing everything
This co-infection has raised concerns that SARS-CoV-2 acquires 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 exchange large parts of their genome with each other and create completely new sequences.
This is a well-known phenomenon in RNA viruses. New influenza variants are generated by a similar mechanism called “reassortment”. The genome of influenza virus, unlike 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 influenza viruses and have been called “mixing vessels” that mix them into new strains. The 2009 H1N1 pandemic virus emerged from a reassortment of human, avian and two swine flu viruses.
With coronaviruses, which contain only one RNA strand 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 this could lead to the generation of new variants. In fact, it is proposed that the ability of SARS-CoV-2 to infect human cells was developed by 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 several variants, if they reproduce in different parts of the body, they will not interact with each other.
Indeed, this was observed in patients, where different quasi-species of coronaviruses were found in the upper and lower respiratory tract, suggesting that the viruses in these places did not mix directly with each other.
Evidence so far does not suggest that multi-variant infection leads to more severe disease. And, although possible, very few cases of co-infection have been reported.
Over 90 per cent of infections in the UK are currently B117 – the so-called Kent variant. With such a high prevalence of a variant in the population, co-infections are unlikely to occur.
However, monitoring this landscape allows scientists to monitor the emergence of these new concerns and to understand and respond to any changes in their transmission or vaccine efficacy.
Maitreyi Shivkumar, Lecturer in Molecular Biology, De Montfort University.
This article is republished from Conversation under a Creative Commons license. Read the original article.