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Understanding COVID-19 Variants*
Keywords and Classifications Regarding COVID-19 Variants and Subvariants
SARS-CoV-2, the virus that causes COVID-19, is ever-evolving. As with all viruses, parts of the SARS-CoV-2 virus' genetic code can change (or mutate) over time. Mutation—when a single change occurs to the genetic code of a virus—happens often. 'Variant' is a term often discussed amongst viral changes or mutations and can be defined as viral genetic code that may contain one or more mutations. Variants can emerge and disappear, but for COVID-19, it is likely new variants will continue to spread and replace older variants over time. The Centers for Disease Control and Prevention (CDC) lists numerous variants and tracks their lineage.1 A lineage is a group of related viruses that share an ancestor; for SARS-CoV-2, all lineages cause COVID-19. Sublineage is the term used to define a direct descendent of a parent lineage. For example, BA.2.75 is a sublineage of BA.2 (of the Omicron variant). When two variants combine to form a new variant—different from both parent lineages—this is termed 'Recombination.' Recombination takes place during the viral replication process and often occurs when a person is infected with two variants at the same time.
Classifying lineages and sublineages allows scientists to convey similarities and differences between viruses, and there are different ways in which SARS-CoV-2 viruses are classified. Their classification often depends on the context and method by which they are communicated. The most used classification system for lineages is Pango, a hierarchical system that often uses alphabetical prefixes (such as J or JN) and numerical suffixes (.1)—in that respect, JN.1 is the assignment given to the strongest SARS-CoV-2 strain at the time of this publication. JN.1 has surpassed HV.1 and is reported as the variant causing nearly half of recorded COVID-19 cases in the U.S. (as of January 2024).
Pango names/classifications can become very long. As the virus evolves, lineages with longer names are sometimes given alphabetic aliases and extended numbering (e.g., "BA" stands for "B.1.1.529," thus BA.2 is the same as B.1.1.529.2).2 More information on the Pango lineage system can be found via Pango Network. For a full list of the current Pango lineages, see cov-lineages.org.
The Nextclade classification system may also be used to illustrate the genetic lineage and sublineages of SARS-CoV-2, and like Pango, acts as a family tree of sequences. Significant sequential branches are given names to represent a "clade" to show they derive from a common ancestor. Nextclade classifications include the two-digit assigned year, followed by a letter indicating order within the assigned year (e.g., "22A" is the first clade designated in 2022 and corresponds to the group of Pango lineages that descended from BA.4, which was circulating in early 2022). The CDC states: "Not every SARS-CoV-2 virus is assigned its own clade by Nextclade. Each potential clade must circulate at a certain frequency for a period of time, show consistent growth in a region, or be assigned a WHO classification. […] These broader definitions offer an alternative naming solution that is meant to reflect significant differences in biology or circulation."3
In a larger, perhaps more widely-known context, the World Health Organization (WHO) chose to name key SARS-CoV-2 variants with "easy to say and remember labels" from the Greek alphabet.4 Many COVID-19 variants have made headlines based on their quick worldwide spread and symptoms. For example, Delta became a widely known "Variant of Concern" (VOC), and Omicron received the same designation a few months later. In the United States, all circulating variants are monitored by the CDC and assigned a category based on their risk.5 Epidemiologists and disease experts rank variants to prepare for potential public health action; variant classification can change over time due to sustained circulation or lack thereof. Such classifications (in order of increasing threat) include:
Variants Being Monitored (VBM):
- VBMs include lineages with potential impact on healthcare countermeasures, lineages that at one time caused more severe disease or transmission but are no longer detected, lineages with many antigenic mutations AND presence in multiple countries with collection dates within 4 weeks, and lineages previously classified as VOI, VOC, or VOHC that have been downgraded due to low circulation levels in the United States.
Variant of Interest (VOI):
- VOIs are logged when the efficacy of diagnostic testing or treatments approved by the U.S. Food and Drug Administration (FDA) is diminished when there is a predicted increase in transmission, outbreak clusters, or severe disease.
- VOIs are monitored in the U.S., as is their potential prevalence to increase in other countries.
Variant of Concern (VOC):
- VOCs are classified as such when there is an increase in transmissibility, more severe disease symptoms and associated hospitalizations or deaths, and/or treatment or diagnostic failures.
- VOCs often require public health action such as notifying WHO, reporting to CDC, establishing local or regional efforts depending on area(s) of transmission, increasing mitigation measures (masking, distancing, testing, etc.), and researching and/or adapting vaccine and treatment effectiveness against the VOC.
The dominant SARS-CoV-2 variant currently spreading in the U.S. is JN.1, which is now classified as a VOC (as of January 2024).
Variant of High Consequence (VOHC):
- As their name suggests, VOHCs have the most impact on medical prevention and intervention methods. When a variant is classified as a VOHC, there is evidence of failed diagnostics, reduction in vaccine effectiveness (high number of vaccinated individuals can become infected), increased severe clinical disease and associated hospitalizations or deaths.
- Like VOIs, VOHCs require WHO notification, CDC reporting, strategic notice of prevention or containment methods, and recommendations to update treatments and vaccines.
The most recent (December 2023) VBMs are of the Omicron lineage. The CDC provides weekly tracking information on the most prevalent variants in circulation.
Are Vaccines Affected by Changing Variants?
A mutation does not always mean that the characteristics or symptoms of a virus will change, but mutations can hinder vaccine effectiveness over time. Like influenza, medical experts track COVID-19 mutations and variants to see which genetic versions of a virus have changed and which could have the potential to cause local, national, and global concern. Those variants are often included in updated vaccines so that patients can receive the most comprehensive protections, and this notion is true for the most recent COVID-19 vaccines: COMIRNATY® COVID-19 Vaccine, Moderna® COVID-19 Vaccine, Novavax COVID-19 Vaccine, and SPIKEVAX® COVID-19 Vaccine.
According to the WHO: "All viruses, including SARS-CoV-2, the virus that causes COVID-19, change over time. Most changes have little to no impact on the virus's properties. However, some changes may affect the virus's properties, such as how easily it spreads, the associated disease severity, or the performance of vaccines, therapeutic medicines, diagnostic tools, or other public health and social measures." (WHO).
Because mutations and variants consistently evolve, some protections can be weakened. Yet, COVID-19 vaccines have been known to significantly reduce infection, severity of symptoms, and transmission — even as new variants emerge. However, breakthrough infections can still occur in fully vaccinated people. Typical COVID-19 mitigation and protection efforts like masking, physical distancing, staying home when feeling sick, and washing hands and commonly touched surfaces can also help prevent viral spread.
At the time of this article's publication, the newest COVID-19 vaccines have been established under Emergency Use Authorization (EUA) to protect against recent SARS-CoV-2 strains circulating in the United States. These vaccines come in two forms: mRNA and adjuvanted/protein subunit.
mRNA
- COMIRNATY® COVID-19 Vaccine (approved for individuals 12 years and older)
- Moderna® COVID-19 Vaccine (approved for individuals 6 months to 11 years of age)
- SPIKEVAX® COVID-19 Vaccine (approved for individuals 12 years and older)
Adjuvanted/Protein Subunit
- Novavax COVID-19 Vaccine (approved for individuals 12 years and older)
Tracking Variants: How the CDC Analyzes and Monitors New COVID-19 Variants
The CDC utilizes genomic surveillance to monitor emerging variants of SARS-CoV-2, the virus causing COVID-19. Various pipelines connect genomic sequence data from the CDC, public health laboratories, and commercial diagnostic laboratories, making it accessible through databases like the National Center for Biotechnology Information (NCBI) and the Global Initiative on Sharing All Influenza Data (GISAID).
Within the CDC National SARS-CoV-2 Strain Surveillance (NS3) System, public health laboratories send de-identified specimens to the CDC for sequencing. The process involves four main stages, resulting in genetic sequence data that is shared in public repositories. Quality control measures are applied throughout, ensuring that published data are accessible to scientists worldwide.
The CDC states: "Rapid virus genomic sequencing data combined with phenotypic data are further used to determine whether COVID-19 tests, treatments, and vaccines authorized or approved for use in the United States will work against emerging variants." The importance of genomic surveillance for public health lies in its ability to rapidly identify circulating variants. Mutations in the virus can lead to different attributes, and surveillance informs public health responses. Regular updates support the improvement of testing, treatment, and vaccination programs, with the potential to adapt vaccines as needed. Detecting more transmissible or severe variants enhances outbreak preparedness and strengthens overall public health responses.
The CDC analyzes the available genomic sequence data and provides weekly updates:
Omicron Variant
Identified: November 2021
Omicron and its subvariants have dominated SARS-CoV-2 strains in the U.S. The original Omicron strain (BA.1) is no longer prevalent, but its subvariants, particularly the new strain EG.5 (nicknamed "Eris") in 2023, are driving most infections, with another strain called BA.2.86 (nicknamed "Pirola") being monitored. These strains are highly contagious, surpassing even the transmissibility of the Delta variant. The spike protein mutations in Omicron, over 30 in total, contribute to its increased transmissibility.
In terms of severity, scientists are still investigating whether current Omicron strains cause more severe disease. The original Omicron was generally less severe, but surges led to notable increases in hospitalizations and deaths in early 2022.
Vaccination remains crucial in preventing severe outcomes. While breakthrough infections are expected, staying up to date with vaccinations is the best defense against Omicron.
Delta Variant
Delta (B.1.617.2) emerged in India in late 2020 and quickly became the predominant version of COVID-19 globally, until it was superseded by Omicron in December 2021.
Delta was a highly contagious version of COVID-19, estimated to be 80 to 90% more transmissible than the Alpha variant. In the U.S., its arrival in mid-2021 led to a rapid reversal of the declining trend in COVID-19 cases and hospitalizations. Even highly vaccinated states experienced surges of COVID-19 in the fall of 2021, prompting calls for COVID-19 boosters.
The Delta variant caused more severe disease, especially in unvaccinated individuals. In response to Delta, the CDC recommended "layered prevention strategies" for both the vaccinated and unvaccinated, including hand hygiene, mask-wearing, and maintaining physical distance in areas with substantial or high transmission. While vaccines were effective, no COVID-19 vaccine provided complete immunity, and vaccinated individuals could still transmit the virus, albeit likely for a shorter duration.
Beta Variant
The B.1.351 variant, also known as Beta, was first identified in South Africa at the end of 2020 and later spread to other countries. Concerns were raised due to its multiple mutations and potential to evade antibodies, though it was not widespread in the U.S.
In terms of contagion, the CDC stated that Beta was approximately 50% more contagious than the original coronavirus strain. Evidence suggested that Beta might be more likely than other variants to result in hospitalization and death.
Alpha Variant
Alpha, also known as B.1.1.7, was the initial highly publicized variant that emerged in Great Britain in November 2020. Infections surged in December of that year, and it quickly spread globally, becoming the dominant variant in the U.S. However, Alpha declined in prominence with the emergence of the more aggressive Delta variant.
Alpha was believed to be more infectious due to certain mutations in its spike protein, making the B.1.1.7 lineage 30 to 50% more contagious than the original SARS-CoV-2 strain. In mid-April 2021, before the dominance of Delta, Alpha constituted 66% of cases in the U.S., as reported by a CDC study.
Moving Forward with COVID-19
SARS-CoV-2 will continue to mutate, resulting in the emergence of new variants or strains. This is a natural occurrence, with many of these genetic changes having no significant impact on an individual's health. However, certain mutations can enhance the spread of new COVID-19 variant(s) or lead to a more severe manifestation of the disease. As COVID-19 variants continue to change, FFF Enterprises will continue to monitor the CDC and WHO recommendations to ensure our selection of COVID-19 vaccines provides the best protection against the virus and severe symptoms.
Other Resources on COVID-19 and its Variants
- CDC's Role in Tracking Variants
- CDC COVID Data Tracker
- Omicron, Delta, Alpha, and More: What To Know About the Coronavirus Variants
- SARS-CoV-2 Variant Classifications and Definitions
- Tracking SARS-CoV-2 variants
- Updated Working Definitions and Primary Actions for SARS-CoV-2 Variants
*Please be advised: Information in this article was accurate at the time of original publication (January 2024). Because information about COVID-19 changes rapidly, FFF Enterprises encourages you to also visit the websites of the Centers for Disease Control & Prevention (CDC), World Health Organization (WHO), and your state and regional government for the most up-to-date information. (You can search here for COVID-19 levels and information by U.S. County).
Footnotes:
- https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-classifications.html#anchor_1679059484954
- https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-classifications.html#:~:text=Pango%20Lineage%20System&text=Lineages%20are%20named%20using%20an,sublineage%20of%20BA.2).
- https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-classifications.html#:~:text=Nextclade%20clade%20names%20consist%20of,was%20circulating%20in%20early%202022.
- https://www.who.int/news/item/31-05-2021-who-announces-simple-easy-to-say-labels-for-sars-cov-2-variants-of-interest-and-concern
- https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-classifications.html#nextclade
- https://covid.cdc.gov/covid-data-tracker/#variant-proportions