Viruses like SARS-CoV-2, which causes COVID-19, are constantly changing as they circulate globally. This natural process of evolution leads to the emergence of new versions of the virus, known as variants. Tracking these genetic changes is a necessity for global public health, as they can alter how the virus behaves. The continuous monitoring of these variants allows scientists and health organizations to anticipate and respond to shifts in the pandemic landscape.
The Biology of Viral Mutation
The emergence of new variants is rooted in the basic mechanics of how RNA viruses, such as SARS-CoV-2, reproduce. When the virus infects a cell, it must copy its genetic material, which is a single strand of ribonucleic acid (RNA), to create new viral particles. This copying is performed by a special enzyme called RNA polymerase.
This copying enzyme is prone to errors, meaning it frequently incorporates the wrong building block into the new RNA strand, which is known as a mutation. These small, random changes create genetic diversity within the viral population. A single genetic change is a mutation, while a variant is a virus that contains one or more of these accumulated mutations. Occasionally, a change provides a selective advantage, such as increased transmissibility or immune evasion. Natural selection then favors these viruses, allowing them to become the dominant circulating variant.
Global Classification Systems
Public health authorities use a structured framework to categorize and communicate the risk posed by emerging SARS-CoV-2 variants. The World Health Organization (WHO) has established a hierarchy to prioritize variants for global monitoring and action. At the lowest level is a Variant Under Monitoring (VUM), which shows genetic changes that might affect the virus’s characteristics, but the evidence of a public health impact is still unclear.
A variant is elevated to a Variant of Interest (VOI) when it shows changes known or predicted to affect characteristics like transmissibility, disease severity, or immune evasion. A VOI is also identified as causing significant community transmission or increasing prevalence in multiple countries, suggesting an emerging risk.
The highest designation is a Variant of Concern (VOC), which meets the VOI criteria but also demonstrates a clear and significant detrimental change. This may include a confirmed increase in transmissibility, a change in disease severity, or a measurable decrease in the effectiveness of public health measures, vaccines, or therapeutics.
To simplify communication to the public, the WHO assigns Greek letters (like Delta or Omicron) to the most significant variants. Scientists continue to use the more detailed Pango lineage system (like B.1.1.529 or JN.1) for genomic surveillance.
Impact on Disease Characteristics
Variant emergence fundamentally changes the practical effects of the virus on human populations. One of the most common changes is increased transmissibility, which is often linked to mutations in the spike protein that sits on the virus’s surface. For instance, some mutations increase the spike protein’s binding affinity to the human ACE2 receptor, the entry point into human cells, thus making the virus spread more easily.
Variants can also display immune evasion, where mutations alter the spike protein just enough to make it less recognizable to antibodies generated from previous infection or vaccination. This evasion can lead to breakthrough infections, even in people with existing immunity.
Finally, the severity of the disease can shift with new variants. While some earlier variants like Delta were associated with increased virulence, the later Omicron variant and its sublineages have generally been associated with a lower likelihood of severe illness, hospitalization, or death. This decreased severity is often attributed to a combination of the variant’s biological characteristics and the high level of population immunity from prior infections and vaccination.
Adapting Vaccination and Treatment
The continuous evolution of SARS-CoV-2 necessitates an ongoing adaptation of medical interventions. This response includes updating the composition of vaccines to maintain protection against circulating variants. The development of bivalent or multivalent vaccines is a direct response to this need.
These vaccines contain genetic instructions for producing the spike proteins from both the original SARS-CoV-2 strain and one or more dominant variants, such as those from the Omicron lineage. This multivalent strategy aims to broaden the immune response, helping the body produce antibodies that can neutralize a wider range of viral versions.
By targeting the spike protein of the most current variants, these adapted vaccines are designed to restore the neutralizing antibody response that may have waned or become less effective against the evolving virus. The effectiveness of therapeutic interventions, particularly monoclonal antibody treatments, is also directly impacted by variant evolution.
Monoclonal antibodies are laboratory-made proteins designed to bind to a specific part of the virus, typically the spike protein, to block infection. As variants acquire mutations in that specific target area, the antibody may no longer be able to bind effectively, rendering the treatment ineffective.
This requires new versions or different classes of antivirals to be used. The need to retire or modify monoclonal antibody treatments is a clear example of how the virus’s constant change drives the medical community to maintain intensive surveillance and rapidly adjust its arsenal of treatments.