COVID-19 Variants Update - Ministry of Health
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COVID-19 Variants Update
Date: 6 July 2021
About this update
During the COVID-19 pandemic, the Ministry of Health has seen high interest in all aspects of the virus from
the scientific and health community and the general public. This update is produced weekly and is designed
to provide new information on variants of the virus that are of interest or concern. The first four pages of
this update are provided as a summary overview, followed by the full technical report.
Note - The World Health Organization (WHO) announced a new naming convention for variants of concern on 31 May 2021 using
Greek letters: Alpha for B.1.1.7; Beta for B.1.351; Gamma for P.1; and Delta for B.1.617.2.
Information gathered in the last week is provided in red text.
Key points
• Epidemiological data continues to indicate that Delta is displacing other variants and is becoming
the dominant variant of concern worldwide.
• Emerging evidence continues to support existing evidence that the Pfizer vaccine remains effective
against the Alpha and Delta variants when two doses are given. The very low rate of breakthrough
infection with the Alpha variant seen in health care workers in a preliminary report from Italy is also
encouraging.
• Data from the COVID Symptom Study app in the UK has shown a high frequency of headache, sore
throat, and runny nose as COVID-19 symptoms, first noted as the Delta variant began to
predominate. This finding is among a select population of app users, has not undergone formal
statistical analysis, and has yet to be substantiated in other reports.
New information in this update
Whole genome sequencing in New Zealand up to 5 July 2021 has identified the following VOCs:
• 184 sequences of Alpha – a decrease of 1 in Alpha sequences since the previous update (due to
reclassification)
• 32 sequences of Beta (including its sub-lineages) - an increase of 1 in Beta sequences since the
previous update
• 8 sequences of Gamma - an increase of 1 in Gamma sequences since the previous update
• 36 sequences of Delta - an increase of 7 Delta sequences since the previous update
The number of sequenced cases of the Delta variant continue to increase. A study from Ontario Canada
demonstrates the transmission advantage of the Delta variant – Delta comprised only 2.2% of whole
genome sequences in early April 2021, rising to 83% by late May 2021.
Evidence continues to show that the full two doses of the Pfizer vaccine are required to provide high levels
of protection against the Delta variant:
• A recent study from Ontario, Canada, estimated ‘real world’ vaccine effectiveness of two doses of
the Pfizer vaccine against symptomatic infection with the Delta variant as 87% and 56% after partial
vaccination. Vaccine effectiveness reported in this study after two doses of Pfizer was 89% against
symptomatic infection with the Alpha variant and 84% for Beta/Gamma.COVID-19 Variants Update
• A laboratory study has reported that neutralising antibodies against the Delta variant are induced
by Pfizer vaccination, with higher antibodies titres seen for sera from people who have had 2
vaccination doses.
Breakthrough infections were reported in a very small proportion of Italian health care workers after two
doses of the Pfizer vaccine in a recent study. The odds ratio for developing SARS CoV-2 infection after
vaccination with respect to unvaccinated subjects reported was 0.13 (95% CI: 0.08-0.19), with an estimated
protective effect of 87% (95% CI: 81-92%). The study also noted that infection with the Alpha variant in the
33 breakthrough cases led to very mild (16 cases; 48%) or asymptomatic disease (17 cases; 52%).
• Up to date information on global cases can be found at:
o Alpha (cov-lineages.org and outbreak.info)
o Beta (cov-lineages.org and outbreak.info)
o Gamma (cov-lineages.org and outbreak.info)
o Delta (cov-lineages.org and outbreak.info)
Global spread of the Delta variant
See Figure 1 below. Note that all cases in New Zealand have been identified at the border. There have been
no community cases of the Delta variant in New Zealand. Also of note, countries vary in the amount of
whole genome sequencing that is completed and how frequently they report data to GISAID.
Figure 1. Delta variant cases identified worldwide[1]
2 of 32COVID-19 Variants Update
VOC Summary
Current VOCs have “evidence of an increase in transmissibility, more severe disease (increased hospitalisations or deaths), significant reduction in neutralisation by
antibodies generated during previous infection or vaccination, reduced effectiveness of treatments or vaccines, or diagnostic detection failures”.[2] Table 1 collates
key information on nomenclature, transmissibility, severity, immune evasion and countries in which the variants have been identified.
Table 1. Summary of characteristics for Variants of Concern as of 6 July 2021. High confidence = orange, medium confidence=yellow, low confidence=green.
Lineage B.1.1.7 Alpha B.1.351 Beta P.1 Gamma B.1.617.2 Delta
Country first identified United Kingdom South Africa Brazil India
501Y.V1, VOC-202012/01, 501Y.V2, VOC-202012/02, 501Y.V3, B.1.1.28.1, VOC-
Other names VOC-21APR-02
VOC-20DEC-01 VOC-20DEC-02 202101/02, VOC-21JAN-02
• ~40-80% more transmissible (R0 • Not well established. • Not established. Preliminary • ~97% more transmissible
Transmissibility ~3.5-5.2)* Preliminary estimate ~50% estimates 40%-160% more compared to non-VOC
more transmissible transmissible • ~40-60% more transmissible
than B.1.1.7 (R0 ~ 5.5-6.5)*.
• Mortality: 60-70% increased • Mortality: Not well established. • Mortality: Not established. One • Mortality: Not well established
mortality compared to previous One report of no increased risk report of no increased risk of • Hospitalisation: Limited
variants of mortality mortality evidence that 2-times the risk of
Severity • Hospitalisation risk: 30-70% • Hospitalisation: Not well • Hospitalisation: Not well hospitalisation compared to
increased risk established. One report of established. One report of B.1.1.7.
approximately 3.6 times risk of approximately 2.6 times risk of
hospitalisation hospitalisation
• Minimal impact on vaccine
effectiveness after 2 doses,
e.g., VE for symptomatic
Immune evasion Minimal Moderate-Strong Moderate-Strong
disease ~88% for Pfizer after 2
doses.
• Reduced VE for 1 dose
69/70 deletion, 144 deletion, T19R, 156-158 deletion, L452R,
Notable mutations N501Y, E484K, K417N N501Y, E484K, K417T
N501Y, P681H, A570D T478K, P681R, D950N
*Assuming R0 for original SARS-CoV-2 of approximately 2.5 to 2.9 [3, 4]COVID-19 Variants Update Background SARS-CoV-2, the virus that causes COVID-19, can undergo genetic mutations. These can occur naturally over time or from selective pressures.[5] The vast majority of mutations do not change the virus in any meaningful way. However some mutations, particularly those relating to virus’s spike protein, can affect the transmissibility of the virus, the disease severity, and the effectiveness of treatments or vaccines.[6] The main driver of new variants is transmission: while there is extensive transmission globally, the opportunity for the emergence of new variants of concern exists. There is also some concern that if infection of SARS-CoV-2 persists for extended periods of time, such as within an person who is immunocompromised, it could serve as a way for mutations to accumulate.[7, 8] Naming of mutations Mutation nomenclature (how mutations are named) describes what has occurred at a specific location of the viral genome.[9] For example, the ‘E484K’ mutation means that at the position 484, the amino acid changed from glutamic acid (E) to lysine (K).[10] When a deletion occurs, the location is provided (e.g., deletion 144). Mutations constitute different lineages of the virus, commonly referred to as ‘variants’. A variant is referred to as a ‘strain’ when it becomes sufficiently different from its parent virus, either by showing distinct physical properties or behaving in a different way for example, in terms of the clinical illness it causes (pathogenic properties) or how it interacts with our immune system (immunological properties). Potentially problematic variants that may have concerning epidemiological, immunological, or pathogenic properties are raised for formal investigation by two main investigative groups - the Public Health England Variant Technical Group[11, 12] and the SARS-CoV-2 Interagency Group in collaboration with the Centers for Disease Control and Prevention (CDC) in the United States (US).[2] Identifying new variants New variants are discovered through whole genome sequencing – a laboratory testing process, for which most countries have had low testing capacity prior to the COVID-19 pandemic. New Zealand now sequences all viable SARS-CoV-2 samples. However, the use and application of whole genome sequencing has varied between countries. Globally genomic surveillance of SARS-CoV-2 remains limited.[13, 14] The Global Initiative on Sharing Avian Influenza Data (GISAID) is a consortium that promotes and provides open access to genomic sequence data. It’s original purpose was for sharing data on avian (bird) flu, but it is now being used in the fight against SARS-CoV-2. Submission of SARS-CoV-2 sequences to GISAID has been key in tracking emerging variants. The USA reports weekly published sequences from the National SARS-CoV-2 Strain Surveillance (NS3) programme, CDC contracts, and other sequencing efforts at the USA CDC here. Sequencing information from the UK can be found at the COG consortium website here.
COVID-19 Variants Update
Variants of Concern
Current VOCs (and alternative names) designated by Public Health England are:
• Alpha: B.1.1.7 VOC-20DEC-01 (VOC-202012/01), GR/501Y.V1
• Beta: B.1.351 VOC-20DEC-02 (VOC-202012/02), GH/501Y.V2
• Gamma: P.1 VOC-21JAN-02 (VOC-202101/02), GR/501Y.V3
• Delta: B.1.617.2 VOC-21APR-02, G/452R.V3
The CDC also categorises variants B.1.427 and B.1.429 as VOCs (“California variants”).
Public Health England removed B.1.1.7 with E484K as a VOC for the UK n 11 June 2021, due to the last
detected sequence in England was 1 March 2021 but will continue monitoring international data.[15]
Public Health England: variant classification
A variant risk assessment framework was published In a Technical Briefing from Public Health England on
11 March 2021, describing how the risk for new variants is determined using the following indicators:
zoonotic emergence and transmission, transmissibility between humans, infection severity, susceptibility
and immunity, vaccines, and drugs and therapeutics.[16] The latest Technical Briefing on the VOCs in
England is linked here.
CDC: variant classification
The link to the CDC’s website describing SARS-CoV-2 variant classifications and definitions is available here.
The CDC is also tracking the proportion of variants circulating in the US for both VOC and VOI.
The CDC has introduced an additional category termed ‘Variant of High Consequence’. This will include
variants that show clear evidence that prevention measures or medical countermeasures have significantly
reduced effectiveness relative to previously circulating variants. As of 6 July 2021, the CDC lists no variants
in this category.
WHO: variant classification
WHO announced a new naming convention for variants on 31 May 2021 using Greek letters. WHO tracking
of variants can be found here. The new naming of variants of concern by the WHO are as follows: Alpha for
B.1.1.7; Beta for B.1.351; Gamma for P.1; and Delta for B.1.617.2.
5 of 32COVID-19 Variants Update
Variants under Investigation and Variants of Interest
Variants with unconfirmed or preliminary evidence of immune evasion, increased transmissibility, or
other concerning features are considered Variants of Interest. They may also be designated as a
‘Variant Under Investigation’ (VUI) by Public Health England.[17]
Variants designated as a VUI are named by a year, month, and number (e.g., VUI-21MAR-02). The CDC
defines a ‘Variant of Interest’ (VOI) as a variant with ‘specific genetic markers that have been
associated with changes to receptor binding, reduced neutralisation by antibodies generated against
previous infection or vaccination, reduced efficacy of treatments, potential diagnostic impact, or
predicted increase in transmissibility or disease severity.[2] The CDC has no naming convention for
VOIs.
The COVID-19 Science and Technical Advisory team is monitoring the developments of VUI/VOIs, which are
summarised below in Table 2.
Table 2. Variants Under Investigation by Public Health England and Variants of Interest by CDC as of 6 July
2021
Earliest Evidence
VUI* Designated by Lineage
documentation
VUI-21JAN-01 Public Health P.2 variant • Spike mutations E484K, D614K, and V1176F.[2]
England and US (descendent of Brazil, April 2020 • Possible reduced antibody neutralisation from studies
(VUI-202101/01) CDC B.1.1.28) on the spike protein mutation E484K.[18]
• Spike mutations A67V, 69/70 deletion, 144del, E484K,
Public Health D614G, Q677H, and F888L.[2]
VUI-21FEB-03 UK and Nigeria,
England and US B.1.525 • First identified in the UK on 2 February 2021.
(VUI-202102/03) December 2020 Detected in 11 countries, including the US, Canada,
CDC
Europe, sub-Saharan Africa and Australia as of March
2021.[16]
No VUI currently • Contains spike mutations L5F, T95I, D253G, E484K,
New York, USA, D614G, and A701V.[2, 19]
assigned by Public US CDC B.1.526
Health England
November 2020 • Reduced antibody neutralisation by monoclonal
antibodies and post-vaccine sera.[2]
VUI-21FEB-04 • Contains spike mutations T95I, 144del, E484K, P681H,
Public Health UK, February
B.1.1.318 D796H. Identified in England in February 2021
(VUI202102/04) England 2021
through routine genomic surveillance.[16]
• Contains spike mutations E484K, S494P, N501Y,
VUI-21MAR-01 Public Health B.1.324.1 with
UK, March 2021 D614G, P681H, and E1111K. Identified in England on
(VUI 202103/01) England E484K 3 March 2021 through routine genomic
surveillance.[16]
• Contains spike mutations E484K, N501Y, P681H, 141-
Philippines,
Public Health 143del.[21, 22]
VUI-21MAR-02 P.3 January 2021 [20,
England • From parent lineage B.1.1.28 (the same as P.1 and P.2
21]
detected in Brazil).[23]
• Designated a VOC by the CDC but is being monitored
Public Health England by Public Health England as of 27 May 2021.
monitoring but has US CDC classified B.1.429/B.1.427 or California, USA, • Characterised by the mutations S13I, W152C, L452R,
not classified as VUI as VOC CAL.20C March 2021 D614G.[2]
or VOC. • May have approximately a 20% increased
transmission compared to previous variants. From
September 2020 through January 2021, the variant
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increased from 0% to 50% of sequenced cases in
California. The increased transmission could be
attributed to a 2-fold increase in viral shedding.[24]
• Genomic surveillance in India reported a variant
VUI-21APR-01, VUI- Public Health B.1.617.1 and India, October containing mutations E484Q and L452R on 24 March
21APR-03 England B.1.617.3. 2020 2021. The implications of these mutations on disease
severity, transmission, and other factors is still under
investigation.[25]
• Designated VUI by Public Health England on 14 May
2021. Contains spike mutations D80G, T95I, G142D,
144del, N439K, E484K, D614G, P681H, I1130V,
D1139H.[26]
• The variant warranted further investigation by Public
Public Health Health England due to the mutations present, mainly
VUI-21MAY-01 AV.1 UK, May 2021 N439K, E484K, P681H and 144del, which have been
England
associated with increased transmission in other
variants. For example, E484K is present in VOC
B.1.351 and P.1, while P681H and 144del is present in
VOC B.1.1.7. Additionally, there appeared to be
localised clustering of the variant in Yorkshire and
Humber regions.[26]
• Designated VUI by Public Health England on 24 May
Public Health Egypt/Thailand, 2021 based on mutations and increased incidence
VUI-21MAY-02 C.36.3
England May 2021 from imported cases. Contains spike S12F, 69-70del,
W152R, R346S, L452R, D614G, Q677H, A899S [27]
VUI-23JUN-01 Public Health C.37 • Spike mutations G75V, T761, del247/253, L452Q,
England F4905, D614G, T859N. Designated due to continued
Lambda
emergence & suspected implications. No evidence to
report to date. [28]
• Small number of cases across 26 countries.[28]
*Public Health England changed the nomenclature for VUI in March 2021, using 2-number year and 3-letter
month. Old naming convention provided in parenthesis for cross-reference.
Additional data on notable VUIs: B.1.617 and sub-lineages
Several pre-prints have investigated antibody neutralisation of B.1.617 and its sub-lineages. Laboratory
data suggests B.1.617 is moderately able to reduce antibody neutralisation from previous infections and
from vaccination completely resistant to monoclonal antibody medicines.[29-31] A 6.8-fold reduction in
neutralisation of Kappa was observed among convalescent sera and vaccinated individuals with the Pfizer
and Moderna vaccines.[30] It was noted that despite the reduction, Kappa was still neutralised in all
vaccinated individuals, implying that mRNA vaccines are likely able to still confer immunity against the
variant. In another pre-print, among 43 participants that received two doses of the Covishield vaccine,
there was a significant two-fold reduction in neutralisation titre of Kappa compared to B.1 variant.[32]
Public Health England has released detailed reports on the B.1.617:
• Public Health England determined that there are 3 clades (otherwise known as lineal descendants
of this variant), named Kappa (B.1.617.1), Delta (B.1.617.2), and B.1.617.3.
• In the technical briefing update on 3 June 2021, secondary attack rates for Kappa – the variant
currently at the centre of the outbreak in Melbourne -- were similar to Delta. Among contacts who
had recently travelled, the secondary attack rate was 2.0% (95% CI: 1.6-2.6%) and was 11.0% (95%
CI: 8.0-15.0%) among contacts without travel.[33]
7 of 32COVID-19 Variants Update
New Zealand cases in MIF/MIQ and global spread
Increased cases of VOC are expected in New Zealand MIF/MIQ facilities as the global presence of these
variants extends geographically and new variants become predominant. There has been a notable increase
in the number of cases of the Delta variant. A pre-print paper demonstrating the transmission advantage of
the Delta variant reported that in Ontario Canada the Delta variant comprised only 2.2% of whole genome
sequences in early April, rising to 83% by late May.[34]
According to GISAID on 10 June 2021, a total of 31,997 sequences have been assigned to the Delta
variant - Europe 24,606; Asia 4,974; North America 2,210; Oceania 163; Africa 36; South America 8; and the
UK 22,619 (reflecting UK sequencing efforts).[35] Figure 1 provides an illustration of the number of
sequenced Delta variant up to 29 June 2021.
Whole genome sequencing in New Zealand up to 5 July 2021 has identified the following VOCs:
• 184 sequences of Alpha – a decrease of 1 in Alpha sequences since the previous update (due to
reclassification)
• 32 sequences of Beta (including its sub-lineages) - an increase of 1 in Beta sequences since the
previous update
• 8 sequences of Gamma - an increase of 1 in Gamma sequences since the previous update
• 36 sequences of Delta - an increase of 7 Delta sequences since the previous update
Up to date information on global cases can be found at:
• Alpha (cov-lineages.org and outbreak.info)
• Beta (cov-lineages.org and outbreak.info)
• Gamma (cov-lineages.org and outbreak.info)
• Delta (cov-lineages.org and outbreak.info)
Review of evidence on specific VOCs
Alpha
Alpha: Genomic characteristics
The Alpha variant is characterised by notable spike protein mutations 69/70 deletion, 144 deletion, N501Y,
P681H, and A570D (Figure 2).[36] There are an additional four spike protein mutations D614G, T716I,
S982A, and D1118H.
Figure 2. Mutations of Alpha (B.1.1.7) (outbreak.info)
8 of 32COVID-19 Variants Update
Alpha: Transmissibility
Several studies have reported increased transmissibility of Alpha, with most studies estimating an increase
between 40-80%.[37-44] From 29 March 2021 through 25 May 2021, Public Health England estimated
Alpha had a secondary attack rate of 8.0% (95% CI: 7.8-8.1%) among contacts that had not travelled or
travel history was unknown.[45] In a study of three childcare centre outbreaks in Germany caused by the
Alpha, the estimated pooled household secondary attack rate was 37.0% (95% CI: 28.0-47.0%).[46] In
Ontario, Canada from 1 March 2021 to 17 April 2021, the household secondary attack rate among 617
confirmed Alpha index cases was 24.3% compared to a secondary attack of 20.2% among 7,555 index cases
of ‘wild-type’ SARS-CoV-2.[47] WHO estimates an increase in the reproductive number for Alpha of 29.0%
(95% CI: 24.0-33.0%) over non-VOCs.[48]
Alpha has gone on to replace previous variants in several countries, for example in the UK, Israel, and
US.[12, 43, 49] In the months from January through May 2021, the proportion of Alpha sequenced
increased from 3% to 70%.[49] Additionally, possible reinfections were identified in 0.7% of cases (95% CI:
0.6-0.8%) in a study of 36,059 participants, although the reinfection rate was not considered higher for
B.1.1.7 than previous variants.[42]
One hypothesis for the increased transmissibility of Alpha relates to the N501Y mutation, which could
provide a selective advantage to the virus by increasing how tightly the spike protein binds to the human
host cell ACE2 receptor.[50-54]
Increased transmission may also be the result of patients with Alpha variant having increased viral loads
compared to those infected with non- Alpha variants.[55-59] However, others have reported no statistical
difference in viral loads for Alpha and proposed that the higher viral loads are the result of ascertainment
bias.[60] A further study found no difference in viral replication between Alpha and earlier variants in
primary human airway epithelial cells.[61]
A modelling study on seasonal transmission of Alpha found there was an association with increased
transmission of the variant in colder and hotter temperatures.[62] However, these data should be
interpreted cautiously, as it was based on modelling and reported in pre-print. Other data suggests
moderate temperatures, such as during spring and fall, may decrease transmission of SARS-CoV-2,[63]
supporting the possibility of a slight seasonal component where more extreme temperatures of the winter
and summer could have an effect on transmission in some places. This is in contrast to some communicable
diseases such as influenza that have a strong seasonal component and are present predominantly in winter.
Alpha: Clinical presentation and disease severity
Clinical presentation
The types of symptoms associated with Alpha are broadly similar to previous variants.[42] The UK Office for
National Statistics undertakes a survey of those testing positive for COVID-19.[64] Individuals with the
Alpha variant may be more likely to have a cough, sore throat, fatigue or myalgia (muscle aches) and may
be less likely to report loss of smell or taste (Figure 3). A separate study reported that patients may present
on hospital admission with hypoxia more often than non-Alpha cases.[65]
9 of 32COVID-19 Variants Update
Figure 3. Comparison of self-reported symptoms for Alpha (light green) and non-Alpha variant (dark green)
(UK Office of National Statistics)
Duration
Some studies have found Alpha to have an increased duration of infection. Daily longitudinal PCR tests
were performed on a cohort of 65 individuals to determine if Alpha was associated with longer duration of
infection.[66] Among seven participants infected with Alpha, the mean overall duration of infection was
13.3 (95% CI: 10.1-16.5) days compared to 8.2 (95% CI: 6.5-9.7) days for 58 participants with non-Alpha.
While the duration of infection was statistically significant, the small sample size should be noted and
interpreted with caution. A modelling study of publicly available sequencing data supported the hypothesis
of Alpha having increased duration of infection.[37]
A further study reported a statistically significant longer duration of RNA positivity in nasopharyngeal swabs
of 16 days among 136 Alpha patients versus 14 days among 965 non-Alpha patients.[57] However, a study
of 36,920 users of the COVID Symptom Study app reported no differences in the duration of symptoms
associated with Alpha.[42]
Hospitalisation and mortality
Multiple large epidemiological studies have reported an increased risk of hospitalisation, intensive care
admissions, and mortality for the Alpha variant compared to previous variants.
Among a cohort of 198,420 patients, the adjusted hazard ratio for critical care admission was 2.0 (95% CI:
1.3-2.5) for Alpha compared to non-Alpha,[67] meaning those infected with the Alpha variant had almost
10 of 32COVID-19 Variants Update
double the risk of critical care admission than those infected with previous variants. A large surveillance
study in seven countries of the European Union found that Alpha cases had 1.7 (95% CI: 1.0-2.9) times the
risk of hospitalisation and 2.3 (95% CI: 1.4-3.5) times the risk of intensive care admission compared to non-
VOC cases.[68] Data from Denmark reported that the Alpha variant patients had a 64% increased risk of
hospitalisation compared to patients with previous variants.[69] Lastly, a matched cohort analysis of 2,821
Alpha cases matched to 2,821 non-Alpha cases in England from October to December 2020 reported a 34%
increased risk in hospitalisation associated with the Alpha variant compared to non-Alpha cases.[70]
Several analyses performed by the New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG)
concluded infection with Alpha B.1.1.7 is associated with an increased risk of hospitalisation.[71]
Regarding mortality, there is substantial evidence of an increased risk of death for those infected with
Alpha compared to previous variants. Using a database of over two million positive SARS-CoV-2 community
tests and 17,452 COVID-19 deaths in England from 1 September 2020 to 14 February 2021, researchers
estimated a mortality hazard ratio of 1.6 (95% CI: 1.4-1.8), meaning a 60% increased risk of death
associated with Alpha compared to previous variants.[72] A matched cohort study of 54,906 pairs
estimated an increase of deaths from 2.5 per 1,000 for non-Alpha cases to 4.1 per 1,000 for B.1.1.7
cases.[73] Additionally, several analyses by NERVTAG estimated an increased risk of mortality between
approximately 30-70% compared to the previous variants.[71] In an adjusted analysis accounting for
demographics and comorbidities, the risk of death for Alpha in England from 16 November 2020 through 5
February 2021 was two-thirds higher (hazard ratio 1.7; 95% CI: 1.3–2.1) compared with non-VOC.[74]
However, in the same matched cohort of 2,821 B.1.1.7 cases described above on risk of hospitalisation,
there was no statistically significant difference in risk of death. From 1 February 2021 through 14 June
2021, Public Health England reported that among 217,228 cases of Alpha, 4,252 had died which is a case
fatality ratio of 2.0%.[45]
A study of only hospitalised patients in the UK reported no association of severe disease and death
between Alpha and non-Alpha.[58] It is important to note that this study evaluates mortality given the
patient is already hospitalised and is therefore an evaluation of a cohort of patients with severe COVID-19.
This suggests that once a patient is admitted to hospital, with regard to mortality at least, the variant is not
relevant.
Alpha: Immunity, vaccines, and therapeutics
Laboratory data
Evidence suggests minimal impact on neutralising activity against the Alpha variant.[75-79] Laboratory
studies with the Pfizer vaccine have shown a majority of individuals produce a detectable antibody
response, although neutralising titres against the Alpha lineage have varied among studies.[75, 80-87] A
study on the Moderna (mRNA-1273) vaccine reported antibodies recognising and neutralising Alpha up to 6
months post-vaccination.[88]
In a clinical trial of the AstraZeneca vaccine, laboratory virus neutralisation activity by vaccine-induced
antibodies was lower against the Alpha variant than against non-Alpha among 311 participants.[89] Vaccine
combinations are being evaluated with regard to variants; a preprint study reported that sera from 26
11 of 32COVID-19 Variants Update
individuals vaccinated with a heterologous AstraZeneca first dose and Pfizer second dose (prime-boost)
vaccination schedule had strong neutralisation activity and T-cell responses against variant Alpha.[90]
Clinical data
Novavax[91] and Moderna[92, 93] reported good vaccine efficacy of their vaccines against the Alpha
variant. Johnson & Johnson/ Janssen did not report on vaccine efficacy with the Alpha variant
specifically.[94]
A study assessing the real-world effectiveness of the Pfizer and AstraZeneca vaccines in the UK (where
there was widespread circulation of Alpha) reported a single dose of either vaccine resulted in an 80%
reduction of hospitalisation.[95] A UK study of staff working in public hospitals found the Pfizer vaccine
effectively prevented both symptomatic and asymptomatic infection despite Alpha being prevalent.[96] A
pre-print of a phase 3 trial of the Novavax (NVX-CoV2373) vaccine among 15,187 participants reported a
vaccine efficacy of 86.3% (95% CI: 71.3-93.5%) against symptomatic Alpha with onset 7 days after the
second dose.[97]
There is no evidence that suggests Alpha can evade immunity and cause breakthrough infections among
those fully vaccinated at a rate higher than previous variants.[89, 96, 98] Even with a very high estimated
prevalence of 94.5% of Alpha in Israel, an analysis of national surveillance data reported high efficacy of the
Pfizer vaccine against infection, asymptomatic infection, and COVID-19 related hospitalisation and
death.[99] In a real-world analysis of the Pfizer vaccine in Qatar, vaccine efficacy against Alpha infection
was estimated to be 89.5% (95% CI: 85.9-92.3%) at 14 or more days after the second dose.[100] A separate
analysis by the same authors evaluated effectiveness after one dose only; the week-by-week vaccine
effectiveness against Alpha infection was 9.9% (95% CI: 0.0-23.7%) 1-7 days after dose 1, 10.1% (95% CI:
0.0-22.6%) 8-14 days after dose 1, and 65.5% (95% CI: 58.2-71.5%) 15-21 days after dose 1.[101] A single
dose of either the Pfizer or Moderna vaccine had a vaccine efficacy at ≥21 days against Alpha infection of
67.0% (95% CI: 57.0-75.0%) among adults ≥70 years old in British Columbia.[102]
Public Health England assessed the effectiveness of the Pfizer (BNT162b2) and AstraZeneca (ChAdOx1)
vaccines against symptomatic disease for both Alpha and Delta.[103] Against symptomatic Alpha, vaccine
effectiveness of the Pfizer vaccine was 49.2% (95% CI: 42.6-55.0%) after one dose and 93.4% (95% CI: 90.4-
95.5%) after two doses. For the AstraZeneca vaccine, vaccine effectiveness was 51.4% (95% CI: 47.3-55.2%)
after one dose and 66.1% (95% CI: 54.0-75.0%) after two doses.[27] However, vaccine effectiveness may be
higher due to some limitations of the data in potentially including individuals with prior infection. In a
separate analysis, vaccine effectiveness against hospitalisation with Alpha after two doses of Pfizer was
95.0% (95% CI: 78.0-99.0%) and 86.0% (95% CI: 53.0-96.0%) after two doses of AstraZeneca.[104]
A pre-print from Ontario, Canada, estimated ‘real world’ vaccine effectiveness of two doses of the Pfizer
vaccine against symptomatic infection with the Alpha variant as 89.0% (95% CI: 86.0-91.0%) and after
partial vaccination as 66% (95% CI: 64.0-68.0%).[105] The study methodology utilised linked population-
wide vaccination, laboratory testing, and health administrative databases to compare data between
individuals who were symptomatic and tested negative on PCR (serving as controls) with individuals who
were symptomatic and tested positive on PCR (considered cases).
12 of 32COVID-19 Variants Update
The protection offered by vaccination of health care workers was investigated in an Italian.[106] Of 3,720 at
a single medical centre who received two doses of the Pfizer vaccine, a total of 33 health care workers had
breakthrough infections, all sequenced as due to the Alpha variant. The odds ratio for developing SARS
CoV-2 infection after vaccination with respect to unvaccinated subjects reported was 0.13 (95% CI: 0.08-
0.19), with an estimated protective effect of 87% (95% CI: 81-92%). Of note, 16 (48%) of those infected
were mildly symptomatic, 17 (42%) were asymptomatic, and none required hospitalisation.
Therapeutics
Alpha can be efficiently neutralised by the monoclonal antibody treatment Bamlanivimab.[107] The FDA
has reviewed data evaluating the combination of casirivimab and imdevimab against Alpha, Beta, P.1,
B.1.427, B.1.429, and B.1.526 and report minimal impact (≤2 fold change) on antibody neutralisation
activity.[108]
B.1.1.7 with E484K mutation
This variant is no longer considered a VOC in the UK as of 11 June 2021 due to no sequences no longer
being detected in the UK.[15] However, some sequences are still being reported internationally and will
continue to be monitored for developments.
B.1.1.7 with E484K mutation: Transmissibility
As above with B.1.1.7 but contains the E484K mutation. The E484K mutation itself may,[75] or may not
impact affinity.[51]
B.1.1.7 with E484K mutation: Clinical presentation and disease severity
As above with B.1.1.7.
B.1.1.7 with E484K mutation: Immunity, vaccines, and therapeutics
Multiple studies have reported a decrease in neutralisation activity against variants with E484K
mutation.[18, 81, 93, 109, 110] This is important because VOC B.1.351 and P.1 also carry the E484K
mutation.
The monoclonal antibody treatment Bamlanivimab may not provide protection against B.1.1.7 with E484K
mutation.[107]
Beta
Beta: Genomic characteristics
Beta is characterised by 17 mutations, with eight spike protein mutations D80A, D215G, 241/243 deletion,
K417N, E484K, N501Y, D614G, and A701V (Figure 4).[111, 112]
13 of 32COVID-19 Variants Update Figure 4. Mutations of variant B.1.351(outbreak.info) Beta: Transmissibility Several of the mutations in Beta, specifically K417N, E484K, and N501Y, may affect the affinity for the spike protein to bind to human host cells. As noted under transmissibility of Alpha, several studies have reported N501Y may increase affinity,[50-54] and when combined with K417N and E484K, studies have estimated between a 3-fold and 19-fold increase in affinity of the Beta variant to bind to human host cells compared to other variants.[51, 52, 110] It is estimated that Beta may be 1.5 (95% CI: 1.2-2.1) times as transmissible as previous variants.[113] Beta was prevalent in a prospective surveillance study in Zimbabwe, accounting for 95% of sequences tested in January 2021.[114] In Ontario, Canada from 1 March 2021 to 17 April 2021, the household secondary attack rate among 96 confirmed Beta index cases was 26.4% compared to a secondary attack of 20.2% among 7,555 index cases of ‘wild-type’ SARS-CoV-2.[47] WHO estimates an increase in the reproductive number for Beta of 25.0% (95% CI: 20.0-30.0%) over non-VOCs.[48] Case reports suggest that reinfection with Beta after prior infection is possible.[115] Beta: Clinical presentation and disease severity There is limited evidence for severity of disease for Beta. A large surveillance study of 23,343 samples across seven countries in the European Union found 436 Beta cases. In this study, Beta cases had 3.6 (95% CI: 2.1-6.2) times the odds of hospitalisation and 3.3 (95% CI: 1.9-5.7) times odds of intensive care admission compared to non-VOC cases. There was no evidence of association of Beta with risk of death after adjusting for age, sex, and week of reporting, where the adjusted odds ratio was 1.1 (95% CI: 0.4-3.4).[68] However, the estimates of ICU admission were small (
COVID-19 Variants Update
Conversely, some studies have reported that T-cell responses to vaccination or previous infection do not
target mutations in B.1351, suggesting T-cell responses are unlikely to be affected.[123-125] A laboratory
study tested two antibodies that target the receptor-binding domain of the spike protein, 1-57 and 2-7, and
found them to be unaffected by Beta.[126]
A study measuring neutralisation activity in 24 serum samples from clinical trials of two vaccine candidates
in China reported a slightly reduced activity against the Beta variant but this was not statistically
significant.[127] The authors note that while their findings suggest Beta does not escape immunity, the
reduced antibody neutralisation may impact overall clinical vaccine efficacy.
Among individuals vaccinated with the Moderna (mRNA-1273) vaccine, there was a 3 to 15-fold reduction
in antibody neutralisation.[88] With regard to duration of immunity, after a six month follow-up, 54%, 58%,
and 79% of individuals had detectable antibodies against pseudovirus, live virus, and ACE2 blocking,
respectively. Moderna is developing a vaccine targeted towards the Beta variant called mRNA-1273.351. In
a clinical study of the mRNA-1273.351 vaccine, individuals were vaccinated with a third dose of either the
original vaccine (mRNA-1273) or the variant targeted vaccine (mRNA-1273.351), six months after their
second dose.[128] The results found increased neutralisation in those given mRNA-1273.351, the targeted
vaccine, compared to those given the original vaccine.
Individuals vaccinated with the Janssen (Ad26.COV2.S) vaccine had 5.0-fold reduced neutralising antibody
titres compared to Wuhan (i.e., the ‘original’ wild-type SARS-CoV-2) variant.[129] However, T-cell and
memory cell responses were preserved, no matter the variant.
With regard to vaccine combinations, sera from 26 individuals vaccinated with a heterologous AstraZeneca
first dose and Pfizer second dose (prime-boost) vaccination schedule had strong neutralisation activity and
T-cell responses against Beta.[90]
Clinical data
Results from Novavax[91], Johnson & Johnson/Janssen[94] and Moderna[92, 93] provide strong evidence
that Beta has the ability to evade vaccine-generated immunity to a significant degree.
Johnson & Johnson/Janssen presented data to the FDA on 26 February showing 94.5% of sequenced cases
from participants in South Africa were Beta, and vaccine efficacy for moderate to severe disease in South
African participants was 64.0% (95% CI: 41.2-78.7%).[130] Data on the Novavax vaccine from a phase 2a/b,
randomised placebo-controlled trial in South Africa found that post-hoc vaccine efficacy in preventing mild
to moderate disease caused by Beta was 51.0% (95% CI: -0.6-76.2%).[131]
The AstraZeneca vaccine had a vaccine efficacy of 10.4% (95% CI: -76.8-54.8%) against mild-to-moderate
illness associated with B.1.351 with onset >14 days after second injection.[132] In this same study, vaccine
efficacy against mild-to-moderate illness associated non-B.1.351 variants with onset >14 days after one
dose was 75.4% (95% CI: 8.9-95.5%). Sample sizes resulted in substantially large confidence intervals. The
South African government halted its rollout of the AstraZeneca vaccine following an analysis that it did not
protect against mild or moderate disease caused by the Beta variant.[133] The World Health Organization
has authorised the AstraZeneca vaccine for emergency use through COVAX.[134]
15 of 32COVID-19 Variants Update
A study from Israel noted breakthrough infections (i.e., being infected by SARS-CoV-2 after receiving a
vaccine) by variant Beta among those vaccinated with the Pfizer vaccine.[98] However, there were only a
total of nine B.1.351 cases in the study. Pfizer has begun evaluating a third dose that is formulated based
on the Beta variant mutations.[135] In a real-world analysis of the Pfizer vaccine in Qatar, vaccine efficacy
against Beta infection was estimated to be 75.0% (95% CI: 70.5-78.9%) against Beta at 14 or more days
after the second dose.[100] In a separate analysis by the same authors evaluating effectiveness after one
dose of the Pfizer vaccine, the week-by-week vaccine effectiveness against Beta infection was 0.0% (95% CI:
0.0-15.8%) 1-7 days after dose 1, 0.0% (95% CI: 0.0-1.2%) 8-14 days after dose 1, and 46.5% (95% CI: 38.7-
53.3%) 15-21 days after dose 1.[101]
Moderna has completed manufacturing of clinical trial material for its Beta variant-specific vaccine
candidate, mRNA-1273.351. It has shipped doses to the National Institutes of Health (NIH) for a Phase 1
clinical trial that will be led and funded by the NIH’s National Institute of Allergy and Infectious
Diseases.[136]
Therapeutics
Monoclonal antibody treatments, including Bamlanivimab and Casirivimab, have been shown to be
ineffective against Beta. Studies have reported either partial neutralisation or no neutralisation.[78, 107,
110, 137-139] The consensus is that escape from monoclonal antibody treatments is due to the E484K,
K417N, and N501Y mutations.
The FDA has reviewed data evaluating the combination of casirivimab and imdevimab against Alpha, Beta,
Gamma, B.1.427, B.1.429, and B.1.526 and report minimal impact (≤2 fold change) on antibody
neutralisation activity.[108]
Gamma
Gamma: Genomic characteristics
The P.1 lineage is characterised by 22 mutations, with 12 spike protein mutations L18F, T20N, P26S, D138Y,
R190S, K417T, E484K, N501Y, D614G, H655Y, T1027I, and V1176F (Figure 5).[140] It is important to note
that E484K and N501Y spike mutations are present in both P.1 and B.1.351. Additionally, the B.1.351
variant contains a K417N mutation, while P.1 is a K417T mutation, meaning an amino acid change occurred
at the same location in both variants, but the amino acid is different. The implications of the different
amino acid between the two variants is unclear, but likely to be similar.
Figure 5. Mutations of variant P.1 (outbreak.info)
Gamma: Transmissibility
Some studies have found Gamma to be more transmissible. In Ontario, Canada from 1 March 2021 to 17
April 2021, the household secondary attack rate among 340 confirmed Gamma index cases was 28.2%
16 of 32COVID-19 Variants Update compared to a secondary attack of 20.2% among 7,555 index cases of ‘wild-type’ SARS-CoV-2.[47] WHO estimates an increase in the reproductive number for Gamma of 38.0% (95% CI: 29.0-48.0%) over non- VOCs.[48] A modelling study fitting data from the Brazilian national health surveillance of hospitalised individuals in Manaus from December 2020 to February 2021, estimated the Gamma variant to be 2.6 (95% CI: 2.4–2.8) times more transmissible than previous variants.[141] Another modelling study estimates that Gamma is 1.7 to 2.4 times more transmissible than earlier variants.[142] The Gamma variant was found to have approximately a 10-fold higher viral load in upper respiratory tracts than non-P.1 infections, suggesting the Gamma variant is more transmissible.[143] However, given the scarcity of data and the number of assumptions that are required for modelling studies and limitations of real-world estimates, increased transmissibility for this variant is suspected but not well established. Gamma: Clinical presentation and disease severity There is limited evidence for severity of disease for Gamma. A large surveillance study of 23,343 samples, of which 352 were P.1 variant, across seven countries in the European Union found 2.6 (95% CI: 1.4-4.8) times the risk of hospitalisation and 2.2 (95% CI: 1.8-2.9) times the risk of intensive care admission compared to non-VOC. There was no association found between Gamma and risk of death, with an adjusted odds ratio of 0.6 (95% CI: 0.3-1.0).[68] However, estimates for ICU admission were small (
COVID-19 Variants Update
generated by previous infection. There have been several case reports of individuals infected with Gamma
after a previous COVID-19 infection.[155-157] A follow-up study in Manaus, Brazil, estimated that
approximately 17% of infections in the second wave (from November 2020 onwards) were reinfections,
presumed to be infections of the Gamma variant. However, there are several limitations to this study: not a
population-wide sample (238 blood donors), small sample (10 reinfections), whole genome sequencing was
not used to determine variant type (Gamma was assumed to be responsible for the reinfection, given the
geographical location, which may include some non-Gamma cases).[158]
Clinical data
A pre-print evaluated the efficacy of the CoronaVac vaccine against symptomatic COVID-19 in an elderly
population in São Paulo State, Brazil.[159] The Gamma variant is considered highly prevalent in this State,
estimated by the authors to be approximately 83%. Among 26,433 COVID-19 cases and 17,622 test-
negative controls, the adjusted vaccine effectiveness ≥ 14 days after the second dose was 41.6% (95% CI:
26.9-53.3%). There was a significant decline in efficacy as age increased, from 61.8% in individuals 70-74 to
28.0% in ≥ 80 years of age.
A single dose of either the Pfizer or Moderna vaccine had a vaccine efficacy at ≥21 days against P.1
infection of 61% (95% CI: 45-72%) among adults ≥70 years old in British Columbia.[102]
Developments will continue to be monitored and updated when information becomes available.
Therapeutics
Monoclonal antibody treatments such as Bamlanivimab and Casirivimab have been shown to be ineffective
against Gamma. Studies have reported either partial neutralisation or no neutralisation by monoclonal
antibody treatments against the Gamma variant.[78, 107, 110, 137-139]
The FDA has reviewed data evaluating the combination of casirivimab and imdevimab against Alpha, Beta,
Gamma, B.1.427, B.1.429, and B.1.526 and report minimal impact (≤2 fold change) on antibody
neutralisation activity.[108]
Delta
Delta: Genomic characteristics
The B.1.617.2 lineage is characterised by spike protein changes T19R, 156-158 deletion, L452R, T478K,
D614G, P681R, and D950N (Figure 6).[160] The L452R has been associated with increased transmissibility
and a reduction in neutralisation by convalescent plasma and some monoclonal antibody medicines [24].
The P681R mutation could potentially have an effect on cell entry and infectivity.[161] A very small number
of sequences of Delta have acquired an additional spike protein mutation K417N which has been
designated AY.1 (Delta with K417N or Delta-AY.1). Few sequences have been detected so far, with 161
genomes identified on GISAID as of 16 June 2021 in 10 countries.[45] The mutation K417N is also found in
Beta and has been linked to immune escape.
18 of 32COVID-19 Variants Update
Figure 6. Mutations of Delta (outbreak.info)
Delta: Transmissibility
The Public Health England risk assessment on 25 June 2021 states that: “Delta continues to demonstrate a
substantially increased growth rate compared to Alpha, across multiple analyses. Secondary attack rates
and household transmission studies support increased transmissibility.”[162]
In the Public Health England technical briefing on 25 June 2021, Delta accounted for approximately 95% of
sequenced (confirmed) cases and 92% of genotyped (probable) cases from 7-21 June 2021.[28] CDC data
shows Delta accounted for 9.5% of sequenced cases in the USA in the 2 weeks to 5 June 2021.[49]
In a preliminary analysis by Public Health England, the odds of household transmission among cases of
Delta were 1.6 (95% CI: 1.3-2.1) times higher than Alpha, meaning Delta was associated with 60% more
household transmission compared to Alpha.[15] Based on contact tracing data in the UK from 29 March
2021 to 25 May 2021,[45] the estimated secondary attack rate for Delta among contacts who had recently
travelled was 2.3% (95% CI: 2.0-2.5%), which is significantly higher than B.1.1.7 at 1.5% (95% CI: 1.3% -
1.6%). Among contacts that had not travelled, the secondary attack rate was approximately 40% higher for
Delta at 11.4% (95% CI: 11.1-11.7%) compared to 8.0% (95% CI: 7.8-8.1%) for Alpha, which implies that
Delta has higher transmissibility than Alpha.
The WHO has reported similar growth rates for Delta [163] and estimated an increase in the reproductive
number for Delta at 97.0% (95% CI: 76.0-117.0%) over non-VOCs.[48] WHO also estimated an increased
reproductive number of 55.0% (95% CI: 43.0-68.0%) for B.1.617.2 over Alpha. This is similar to the
estimated 40% increased secondary attack rate, with overlapping confidence intervals, for Delta over Alpha
reported above by Public Health England.
Delta: Clinical presentation and disease severity
Public Health England notes while there may be an increased risk of hospitalisation with the Delta variant
compared to the Alpha variant, they continue to rate their assessment of change in severity as low
confidence.[162] Among 43,338 sequence-confirmed cases between 29 March 2021 and 5 June 2021 in
England, Public Health England found a significantly increased risk of hospitalisation for Delta, with a hazard
ratio of 2.3 (95% CI: 1.3-3.9) compared to Alpha.[15] Similar analyses in Scotland found that cases of Delta
had 1.9 (95% CI: 1.4-2.5) times the risk of hospitalisation compared to Alpha (using S-gene status as a proxy
for the two variants).[164] From 1 February 2021 through 14 June 2021, Public Health England reported
that among 31,132 cases of Delta, 17 had died which is a case fatality of 0.3%.[45] However, since mortality
is a lagged indicator (i.e., a lengthy follow up period is required), an extensive analysis to control for other
factors has not yet been completed.
Media reports[165] of data from the COVID Symptom Study reported that the most commonly reported
symptoms were headache, sore throat and runny nose. However, this result should be interpreted with
caution as the data collected by an app is based on a self-selected sample or self-reported symptoms. Also,
19 of 32COVID-19 Variants Update
due to the successful vaccination rollout in the elderly in the UK, the majority of cases are in younger age
groups (compared to previously) and therefore any comparison of the symptom profile with previously
circulating variants, is confounded with age. Data from the COVID Symptom Study app in the UK has shown
a high frequency of headache, sore throat and runny nose as COVID-19 symptoms, first noted as the Delta
variant began to predominate.[166] This finding is among a select population of app users, has not
undergone formal statistical analysis, and has yet to be substantiated in other reports.
Cases in the UK tend to be younger age groups than seen previously, likely due to vaccination of older
groups:[15] Pre-print data from the REal-time Assessment of Community Transmission - 1 (REACT-1) study
in the UK also reports higher COVID-19 infection rates in younger than older people. The study involves
self-administered throat and nose swabs for RT-PCR testing from random population sampling. During the
study period when Delta accounted for approximately 90% of overall samples, higher rates of swab
positivity were seen in young adults (18-24 years) and younger children (5-12 years) than in adults over 65
years, an age-group that is largely vaccinated. [167]
Public Health England on 25 June 2021 reported that based on routine national testing data mean PCR cycle
threshold (Ct) values appear to be persistently lower in Delta than Alpha cases. This is composite data and
does not provide information at the level of individual cases.[28]. This aligns with a study of 100
‘breakthrough’ infections with Delta (i.e., infections after vaccination) from the Cambridge Institute of
Therapeutic Immunology & Infectious Disease, that Delta has higher respiratory viral loads compared to
non-Delta infections, as indicated by lower cycle-thresholds (Ct value of 16.5 versus 19 for non-Delta
infections).[168]
Delta: Immunity, vaccines, and therapeutics
Laboratory data
Two doses of the Pfizer (BNT162b2) vaccine elicited detectable antibodies in 150 (94.3%) of 159
participants against Delta, although there was a 5.8-fold reduction in neutralising antibodies.[86] A pre-
print reported similar reductions in neutralisation and antibody titres.[35] In another pre-print, individuals
receiving two doses of the Pfizer vaccine had neutralising activity reduced 3- to 6-fold against Delta,[169]
whereas sera from individuals vaccinated with AstraZeneca had poor or no neutralising activity against
Delta.
With regard to vaccine combinations, sera from 26 individuals vaccinated with a heterologous AstraZeneca
first dose and Pfizer second dose (prime-boost) vaccination schedule had strong neutralisation activity and
T-cell responses against variant B.1.617, although the authors did not specify the sub-lineage, which may be
clarified after peer-review.[90]
Clinical data
Other evidence to date suggests that vaccines remain effective against the Delta variant but that the full
two doses are required to provide high levels of protection.
20 of 32COVID-19 Variants Update
Public Health England assessed the effectiveness of the Pfizer and AstraZeneca vaccines against
symptomatic disease for both Alpha and Delta.[103] Against symptomatic Delta, vaccine effectiveness of
the Pfizer vaccine was 33.2% (95% CI: 8.3-51.4%) after one dose and 87.9% (95% CI: 78.2-93.2%) after two
doses, slightly lower than seen in some other real-world studies but within confidence limits. For the
AstraZeneca vaccine, vaccine effectiveness was 32.9% (95% CI: 19.3-44.3%) after one dose and 59.8% (95%
CI: 28.9-77.3%) after two doses against symptomatic disease.[27] In a separate analysis, vaccine efficacy
against hospitalization with the Delta variant was 96.0% (95% CI: 85.0-98.0%) after two doses of Pfizer and
92.0% (95% CI: 75.0-97.0%) after two doses of AstraZeneca.[104]
This data is supported by a study from Ontario, Canada, estimating ‘real world’ vaccine effectiveness of two
doses of the Pfizer vaccine against symptomatic infection with the Delta variant as 87.0% (95% CI: 64.0–
95.0%), comparable to the levels of effectiveness seen for Alpha (89.0%; 95% CI: 86.0-91.0%) and
Beta/Gamma (84.0%; 95% CI: 69.0-92.0%).[105] Vaccine effectiveness against Delta after partial vaccination
with the Pfizer vaccine was reported as 56% versus 66% against the Alpha variant. The study methodology
utilised linked population-wide vaccination, laboratory testing, and health administrative databases to
compare data between individuals who were symptomatic and tested negative on PCR (serving as controls)
with individuals who were symptomatic and tested positive on PCR (considered cases). Limitations included
the possibility that some specimens designated Delta may have been non-VOC specimens.
A pre-print reported on the rise of the Delta and Gamma variants compared to the Alpha variant across the
USA. Grouping COVID-19 test data according to whether from counties with high or low vaccination rates,
they found a greater increase in cases of the Delta variant in counties with less people vaccinated. These
findings are preliminary and yet to be subjected to peer review. However, they provide some limited
further data in support of vaccine effectiveness against this variant. [170]
21 of 32COVID-19 Variants Update
Glossary of Terms
The AstraZeneca vaccine AZD1222 or ChAdOx1
The Pfizer/BioNTech vaccine Comirnaty/BNT162b2
This is a consortium that promotes and provides open access to SARS-CoV-2
Global Initiative on Sharing
genomic sequence data. It’s original purpose was for sharing data on avian (bird)
Avian Influenza Data (GISAID)
flu.
The ability of the virus to evade our body’s immune response. See also Immune
Immune evasion
response.
The response of our immune system to an infection. It includes development of
Immune response specific antibodies to the virus and also cell-mediated responses (triggered by T
cells).
An antibody produced by a single cell line and consisting of identical antibody
Monoclonal antibody
molecules. See also Immune response.
A type of drug that uses monoclonal antibodies to bind to certain cells or
Monoclonal antibody therapy proteins to stimulate the body’s immune system to attack those cells/proteins.
E.g., Bamlanivimab.
Small change made to the pattern of nucleotides that make up the virus. These
Mutation occur as the virus spreads and replicates. Most do not confer a benefit to the
virus.
Mutation nomenclature (i.e., how they are named), describes what occurred at a
specific location of the genome. For example, the ‘E484K’ mutation means that at
Naming mutations
the position 484, the amino acid changed from glutamic acid (E) to lysine (K).
When a deletion occurs, the location is provided (e.g., deletion 144).
N-terminal domain Part of the spike protein of the SARS-CoV-2 virus.
The reproductive number R0 (R-naught), is a measure of how contagious a
disease is. It is the average number of people who would catch a disease from
Reproductive number, R0
one infected individual when there are no control measures in place, e.g.,
vaccination, lockdowns.
The ‘effective R’ (Reff) is the R observed when control measures are in place. Reff
can therefore change depending on the control measures currently enacted in a
Effective reproductive
particular population. In general, whenever R is less than 1, i.e., an infected
number, Reff
person goes on to infect less than one person on average, then the prevalence of
the disease would be expected to decrease
A ‘watery’ colourless component of blood in which red blood cells (erythrocytes),
Serum (plural Sera)
white blood cells (leucocytes) and platelets are suspended.
Having detectable antibodies against the virus as measured by a blood
Seropositive
(serological) test.
Viruses with mutations are referred to as variants of the original virus. New
Variant
variants of SARS-CoV-2 have been emerging as the virus has spread and evolved.
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