Frequently Asked Questions
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A virus is a genetic code (DNA or RNA) enveloped in a lipid and protein capsule. Unlike other living things, viruses cannot replicate alone; they require host cells. In order to infect host cells, viruses have various adaptations to allow penetration into the host cell. For example, in the case of SARS-CoV-2, there are multiple spikes with receptors and enzymes allowing for binding to, and penetration into, the host cell. Once within the host cell, the virus can then replicate, usually killing the host cell in the process, and causing physical manifestations of disease. Viruses cannot be killed by antibiotics. Vaccines, anti-viral medications, and certain treatments such as monoclonal antibodies are the only pharmaceutical methods to reduce viral disease.
Viruses constantly change and evolve through mutation. A mutation is a change to the genetic material of the virus, occurring during replication. Most mutations are not dangerous, but some can be. Since the genetic material of the virus determines how it infects hosts, mutations can alter numerous things. Some possible changes include increase in transmissibility (how easily it can spread), increase in virulence (how severe it is), immune escape (resistance to vaccines), and reduce the efficacy of some treatments.
A variant is a mutated strain that shares the same inherited set of distinctive mutation(s). Variants often contain multiple mutations. Using a fruit analogy, think of the variety of apples. Red Delicious, Granny Smith, and Honeycrisp are “variants” of apples. Different variants have different mutations, each of which can have a different effect. A single variant may contain multiple mutations compared to its parent. Because the situation is continuing to evolve rapidly, and more variants are expected to emerge, there are a number of concerns due to the unknowns. Mutations can alter transmissibility and severity, as well as cause resistance to medications and immune escape (resistance to antibodies). Other unknowns exist as well, such as the impact on those with pre-existing conditions. Each of these factors can alter the risk to global travel.
The WHO are constantly monitoring and assessing variant viruses which are identified, which they term 'Variants Under Monitoring' (VUM). The WHO categorizes COVID-19 variants of significance into 'Variant of Concern' (VOC), and 'Variant of Interest' (VOI). As the situation evolves, variants may be re-categorised. The WHO defines the two as:
Variant of Concern: Shows an increase in transmissibility, has an increase in virulence or clinical presentation (symptoms), or a decrease in effectiveness of public health measures such as vaccination, social distancing, or pharmaceutical treatments.
Variant of Interest: Shows genetic changes that may affect transmissibility, severity, immune, diagnostic or therapeutic escape. AND has been identified to cause significant transmission, or multiple clusters with increasing prevalence, or other indicators of emerging risk.
VOCs and VOIs may be downgraded to former VOCs/VOIs when they are “conclusively demonstrated to no longer pose a major added risk to global public health compared to other circulating SARS-CoV-2 variants.”
The United States Centers for Disease Control and Prevention has a two additional categories and may classify individual variants in a different category to WHO:
Variant Being Monitored (VBM): variants for which there are data indicating a potential or clear impact on approved or authorized medical countermeasures or that has been associated with more severe disease or increased transmission but are no longer detected or are circulating at very low levels in the United States, and as such, do not pose a significant and imminent risk to public health in the United States.
Variant of High Consequence (VOHC): clear evidence that prevention measures or medical countermeasures (MCMs) have significantly reduced effectiveness relative to previously circulating variants.
On 31 May 2021, the WHO established a naming convention based on letters of the Greek Alphabet. Media and other reporting agencies sometimes label these by the geographical area where they were first discovered, where previously it was more accurate to classify them by their lineage numbers.
Several variants have already been identified, and as more locations undertake genetic sequencing, more variants will emerge. It is impossible to say how many will emerge during the course of the pandemic. While not all variants are VOI or VOC, it is expected some may be more transmissible, potentially cause more severe disease (lethality), and / or evade current vaccines (immune escape).
Vaccination produces a ‘polyclonal’ response that targets several parts of the Spike protein. The virus would likely need to accumulate multiple mutations in the Spike protein to evade immunity induced by a vaccine. According to the CDC, “So far, studies suggest that antibodies generated through vaccination with currently authorized vaccines recognize these variants. This is being closely investigated and more studies are underway.” If, as ascertained by preliminary studies, neutralizing function is indeed diminished but not eliminated, then it could suggest that a strong vaccine response will protect against the variant. However, as noted below, certain vaccines have reduced efficacy against specific variants.
The European Centres for Disease Control and Prevention (ECDC) have also stated: "The COVID-19 vaccines that are currently being rolled out through vaccination programmes are expected to provide at least some protection against new virus variants because they all lead to a broad immune response. If any of these vaccines prove to be less effective against one or more variants, it will be possible to change the composition of the vaccine to protect against those variants."
Regardless, it is vital for communities to have rigorous compliance with non-pharmaceutical interventions in addition to getting vaccinated.
Several clinical trials are underway examining the efficacy of a booster overall, as well as in the context of efficacy against variants.
Some countries are recommending boosters for people at higher risk of severe disease, while others are using them more broadly. These recommendations are made for COVID-19 in general, not for particular variants. More information on countries offering booster shots can be found here.
The WHO releases a weekly report on the epidemiological situation. The most current report, and archived reports, may be found here.
Outbreak.info (a project at Scripps Research supported by the National Institute for Allergy and Infectious Diseases, National Center for Data to Health, and Centers for Disease Control and Prevention) has a dashboard of variants. The dashboard allows customisable reports by variant, location and time.
Background: This variant was first identified in the United Kingdom in September 2020 and was classified as a Variant of Concern on 18 December 2020.
Transmissibility: The Alpha variant has shown 30 to 70% greater transmissibility.
Severity: Emerging evidence indicates this strain can result in more severe COVID-19 disease. While initially there was no evidence of more severe disease, more recent reports indicate that this variant can lead to an increase in hospitalization and death.
Vaccine Efficacy: Studies have found reduced vaccine efficacy. Several Vaccine-producing companies (Pfizer-BioNTech, Moderna, AstraZeneca-Oxford, Johnson and Johnson, Novavax) have confirmed that their vaccines, based on different designs, can all be effective against this variant.
The Novavax vaccine has shown an efficacy of 89.3% in its Phase 3 clinical trial conducted in the UK. Interestingly, a study published in The New England Journal of Medicine found the Oxford/AstraZeneca vaccine is approximately 75% effective against the Alpha variant. This is in comparison to the overall efficacy prior to the emergence of variants, measured at 66.7%. The same study found that the mRNA vaccines (Pfizer/BioNTech and Moderna), had no reduced efficacy. A second study in The New England Journal of Medicine, found the Pfizer/BioNTech vaccine was 93.7% effective.
Treatment Efficacy: Monoclonal antibody treatments remain effective against this variant. Some evidence shows a reduction in efficacy of convalescent plasma.
Background: This variant was first identified in South Africa in May 2020. It was classified as a Variant of Concern on 18 December 2020.
Transmissibility: Evidence has shown approximately 50% greater transmissibility.
Severity: Studies are ongoing, but there is no peer-reviewed evidence at this time showing increased severity.
Vaccine Efficacy: The Beta variant has significantly reduced efficacy to the Oxford/AstraZeneca vaccine. A study published in The New England Journal of Medicine found the Oxford/AstraZeneca vaccine “did not show protection against mild to moderate COVID-19 due to the [Beta] variant.” The same study noted interim results found the Johnson & Johnson vaccine to be 57% effective against moderate to severe COVID-19 and 89% effective against severe cases. The Sputnik V vaccine has reduced efficacy, and one study found Novavax had 60% efficacy in adults that are HIV negative.
Treatment Efficacy: Studies have found that monoclonal antibody treatments, Bamlanivimab and Etesivimab, do not effectively neutralise this variant.
Background: This variant was first identified in Japan and Brazil in November 2020. It was classified as a Variant of Concern on 11 January 2021.
Transmissibility: Some evidence shows this variant is more than twice as easy to transmit as the wild-type.
Severity: Data regarding hospitalisation rates is still pending.
Vaccine Efficacy: Gamma has multiple mutations that help it evade antibodies from previous infection and from vaccination.
Treatment Efficacy: The effects of Bamlanivimab and Etesevimab are significantly reduced against this variant, and it has shown reduced neutralization by convalescent plasma.
Background: The B.1.617 variant was first identified in India, and several sub-lineages, including the Delta variant B.1.617.2, and the Kappa variant B.1.617.1.
Transmissibility: Studies have found nearly 30% increase compared to the wild-type. A study published in the journal Eurosurveillance found a 29% increase to transmissibility compared to the wild type, and a study in BMJ found 60% increase in transmissibility compared to the Alpha variant. The CDC notes the Delta variant is nearly twice as contagious as other variants.
A pre-print study found viral loads of the Delta variant were 1,200 times higher; high viral load is associated with easier transmissibility. The virus was also detectable on only four days after exposure, instead of the usual six days with the wild strain, meaning this strain spreads more easily and rapidly.
Severity: Some evidence has shown a higher frequency of hospitalisation and increased severity associated with this variant.
Vaccine Efficacy: Several Vaccine-producing companies (Pfizer-BioNTech, Moderna, Oxford/AstraZeneca. Johnson & Johnson, Novavax) have confirmed that their vaccines, based on different designs, can all be effective against this variant. However, the Delta variant has multiple mutations including at least one known to reduce antibody neutralisation; concentrations are 3 to 16 times lower. One study in BMJ, found the Pfizer/BioNTech vaccine was 88% effective and the Oxford/AstraZeneca vaccine was 60% effective. Both vaccines have shown greater than 90% efficacy at preventing severe disease requiring hospitalisation. The Pfizer/BioNTech and Oxford/AstraZeneca vaccines also showed an efficacy of only about 30% after the first dose.
A second study in The New England Journal of Medicine, found the Pfizer/BioNTech vaccine was 88% effective against the Delta strain, mirroring the findings of BMJ. The Oxford/AstraZeneca vaccine was found to be 67% effective.
This variant has also shown immune escape in those who were previously infected with a different strain, but remain unvaccinated. Immune escape has also occurred in people previously vaccinated. The CDC confirms that fully vaccinated individuals can still transmit the Delta variant, though for a shorter period of time than unvaccinated individuals.
However, as this is a more easily transmissible variant, it is essential that correct wearing of masks, cough etiquette, handwashing and physical distancing are rigorously and continually applied. Similarly, it is more important than ever to avoid crowded environments, particularly bars or clubs, where there is limited ventilation and mask-wearing is reduced.
Treatment Efficacy: Studies have found reduced efficacy for monoclonal antibodies. At least one unique mutation has been identified as the likely cause in this strain. The medication Bamlanivimab was found in one study to have little to no effect on the Delta Variant, though Etesivimab, Casirivimab and Imdevimab remained active. One study found monoclonal antibody medication Bamlanivimab, had little to no effect on the Delta variant, though Etesivimab, Casirivimab, and Imdevimab remained active.
Background: The Lambda variant was first detected in Peru in August 2020.
Transmissibility: Some evidence has shown an increase of 64%, and that it is likely more infectious than the Gamma and Alpha variants. Data are lacking.
Severity: Data regarding hospitalisation rates are still pending.
Vaccine Efficacy: A study by the University of Chile found the CoronaVac vaccine was only 3% effective after the first dose, but increased to 56% after the second dose. Sinovac had a similar efficacy profile; 50.4% effective after the second dose. Pre-print evidence indicates that the mRNA vaccines such as Pfizer/BioNTech and Moderna have a slight reduction but remain effective.
Treatment Efficacy: Data are lacking, but preliminary evidence indicates that monoclonal antibody treatments will remain effective.
Background: The Mu variant was first detected in Colombia in January 2021.
Transmissibility: Data is lacking about transmission rates.
Severity: Data regarding hospitalisation rates are still pending.
Vaccine Efficacy: Several mutations suggest it could be more resistant to vaccines. Preliminary data shows Mu has reduced vaccine effectiveness similar to the Beta variant. More research is required
Treatment Efficacy: Data is lacking.
WHO Variant page: https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/
US CDC Variant page: https://www.cdc.gov/coronavirus/2019-ncov/variants/variant.html
US CDC Variant tracker: https://www.cdc.gov/coronavirus/2019-ncov/variants/index.html
Medical Microbiology 4th edition – Chapter 43 Viral Genetics: https://www.ncbi.nlm.nih.gov/books/NBK8439/