Recently, scientists in Brazil reported that two people became infected simultaneously with two different variants of SARS-CoV-2, the virus that causes COVID-19.
This coinfection seemed to have no effect on the severity of the patients ’disease and 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 with other respiratory viruses, such as grip.
This has raised questions about how these viruses can interact in an infected person and what they can mean to generate new variants.
Viruses are masters of evolution, constantly mutating and creating new variants with each cycle of replication. Selective pressures on the host, such as our immune response, also drive these adaptations.
Most of these mutations will not have a significant effect on the virus. But those that give the virus an advantage (e.g., by increasing its ability to replicate or evade the immune system) are a cause for concern and should be closely monitored.
The appearance of these mutations is due to the error-prone replication machinery used by viruses. 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 not identical sequences.
Interactions with host cells and the immune system determine the relative frequencies of individual variants, and these coexisting variants can affect disease progression or the functioning of treatments.
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 patients infected with SARS-CoV-2.
Detection of multiple variants in a person may be the result of coinfection by the different variants, or the generation of mutations within the patient after the initial infection.
One way to discriminate these two scenarios is by comparing the sequences of the variants circulating in the population with those of the patient.
In the Brazilian study mentioned above, the identified variants corresponded to different lineages that had been previously detected in the population, which involved coinfection by the two variants.
Mixing it all up
This co-infection has opened up concerns for SARS-CoV-2 to acquire 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 known phenomenon in RNA viruses. New variants of the flu 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 and combine to produce viruses with a new combination of genes. Interestingly, pigs can become infected with different strains of the flu virus, and they have been called “mixing vessels” that mix them into new strains. The 2009 H1N1 pandemic virus emerged from a reassortment of a human, avian and two swine flu virus.
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.
Recombination tests have 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 has been developed by recombination of the ear protein between closely related animal coronaviruses.
It is important to note that this requires both viruses to infect the same cell. Even if a person is infected with several variants, if it replicates in different parts of the body, it will not interact with each other.
In fact, this was seen in patients, where different quasi-species of coronavirus were found in the upper and lower respiratory tract, suggesting that viruses from these sites did not mix directly with each other.
Evidence so far does not suggest that infection with more than one variant leads to more serious disease. And, while it is possible, very few cases of coinfection have been reported.
Currently, more than 90 per cent of infections in the UK are due to B117, the so-called Kent variant. With such a high prevalence of a variant in the population, coinfections are unlikely to occur.
However, monitoring this scenario allows scientists to track the emergence of these new worrying variants and to understand and respond to any changes in their vaccine transmission or effectiveness.
Maitreyi Shivkumar, Professor of Molecular Biology at De Montfort University.
This article is republished from The Conversation under a Creative Commons license. Read the original article.