Variants, Lineages, and Strains of Coronavirus
All viruses mutate. How fast depends on several factors. Viruses with an RNA genome tend to mutate faster than viruses with a DNA genome. This is because RNA viruses have less ability to fix errors when their genetic material is copied to make virus particles inside infected cells. So every time a virus replicates, there is the chance of a mutation occurring.
Most mutations do not change the encoded viral protein. These are considered “silent” mutations. Others do change the amino acid sequence of the encoded viral protein. However, most mutations have no functional consequence for the virus. The amino acid change does not make the virus pathogenic or not pathogenic (able to cause disease), more or less transmissible (contagious), or more or less disease causing (virulent). So, these mutations are functionally inert. Some mutations may be functionally inert to the virus but alter the ability of the infected host to recognize and eliminate the virus. These do not alter the function of the viral protein, but they do change the immunogenicity of the viral protein, which can impact virulence and transmissibility.
Mutations can result in a new “lineage” of the virus. This is not the same as a new strain. Tracking these lineages can be very useful for determining how a virus spread through communities or populations (Figure 1). For a cool interactive that shows how the various lineages of SARS-CoV-2, which causes COVID-19, spread throughout the globe visit nextstrain.org/ncov.
Mutations that alter any of the following can lead to a new strain:
Not all changes that affect immunogenicity of the viral protein affect the function of the viral protein, and not all changes that alter viral protein function affect immunogenicity (Figure 2).
How do strains contribute to the response to vaccines?
If a mutation affects the part of a virus that is used in a vaccine or that the immune system uses to neutralize the virus, then this new variant becomes a strain that can infect people who have previously been vaccinated or previously infected. This is why a new vaccine is needed for the seasonal flu each year. The virus mutates so that the previous vaccine no longer provides an effective immune response to the new strain of the same influenza virus.
It is unknown if SARS-CoV-2 will mutate such that long-lasting immunity will not be achievable. Assuming that one or more vaccines can be developed to the current variants, future mutations could result in the necessity of new vaccines to maintain immunity.
Another way that the term strain is used is when a particular variant of the virus (the virus with a specific set of mutations) becomes the dominant variant in a population. This can relate to functional mutations or mutations that alter immunogenicity, or it can relate to how that variant was spread. For example, if there was a particular “super-spreading” individual that infected many people in a population, the variant in that individual can become the main form in a population even if the variations do not affect function or immunogenicity. In this case, an existing vaccine would work against this dominant variant because the proteins that trigger the immune response would be unaffected.
This dual use of the term strain can be confusing. It can mean the most common variant of a virus in a population, or it can mean a functionally or immunogenetically different version of the virus. Reports in the popular press, and even the scientific literature, will occasionally use the words “strain” and “lineage” as if they mean the same thing. Some press outlets have claimed that there are >1000 “strains” of the SARS-CoV-2 virus, but this is incorrect. There are >1000 lineages, but far fewer strains (likely between 1 and 10, so far in the world). Researchers are working to determine how many medically relevant strains are circulating and what the consequences are for treatment and vaccine development.
Until there is clear evidence supporting functional or immunogenic differences among the variants, it is appropriate to consider all of these lineages of the same virus.
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