Three for three: Understanding the 3 Covid-19 variants circulating during SA’s third wave

At the end of May, South Africa moved to an increased lockdown alert level in anticipation of the country’s third wave and a rise in SARS-CoV-2 infections Currently, South Africa’s epidemic is dominated and shaped …


  • At the end of May, South Africa
    moved to an increased lockdown alert level in anticipation of the country’s
    third wave and a rise in SARS-CoV-2 infections
  • Currently, South Africa’s epidemic
    is dominated and shaped by the Beta variant which was first identified in the
    Eastern Cape in October
  • Two other variants – Alpha and
    Delta – have been detected in South Africa and could potentially shape what future
    outbreaks look like

South Africa officially entered its third wave on Thursday, 10 June (according to the formula the country uses) amidst a slower than expected vaccine
roll-out, hampered by the lack of availability of shots.

Our infections are rising at a concerning pace.

On Thursday, when South Africa saw 9 149 new
Covid-19 cases, the proportion of tests which came out positive was 15.7% – significantly above the World Health
Organisation’s (WHO) threshold of 5%, which indicates that
the pandemic is out of control. The rolling seven-day average on 8 June, which
is a way to look at such figures over a period of time, was 13.9%.

We don’t yet know how long or how severe this
wave will be, but we do know that the country’s second wave, which started
towards the end of November, caught many off-guard by hitting much earlier than
anticipated – it was also a much more severe wave than anticipated.

During the first wave, the peak of daily infections was 13 944 on 24 July
last year, whereas the highest number of cases during the second wave was 21 980 on 8 January 2021.

The driving force behind this sharp increase in
cases was the emergence of a new form of the virus called 501Y.V2 – or as it has recently been dubbed by
the World Health Organisation, the Beta variant.

What was previously thought to be a relatively
stable virus had rapidly evolved in a way that helped make it more
transmissible and better able to circumvent the body’s protective response
against the original form of the virus.

As we approach the third wave, here’s a look at
which variants are currently circulating in South Africa – and how they could
potentially influence our third wave.

What variants are currently
circulating in South Africa?

The main form of the SARS-CoV-2 virus in South
Africa is the 501Y.V2 or Beta variant – it still accounts for over 90% of Covid-19 cases (based on our genomic data), says Richard Lessells, who was part of the
team that first identified the variant.

Lessells works at the KwaZulu-Natal
Research Innovation and Sequencing Platform (KRISP)
at the University
of KwaZulu-Natal. KRISP is part of the Network for Genomic Surveillance in
South Africa, a
consortium that tracks how the coronavirus is evolving in South Africa. The
consortium also monitors the virus for new mutations that may be cause for
concern. They do this with something called genomic sequencing, a process which
unravels the genetic code of the virus.

Since about March last year, the team has
sequenced around 8 100 virus samples of SARS-CoV-2 in South Africa, Lessells
says. This works out to an average of between 500 and 600 samples per month – although this number increases during waves.

By continuously tracking the virus in this way,
the consortium is able to detect when new variants appear in the country.

For example, on 8 May the National Institute for
Communicable Diseases (NICD) issued a statement saying South Africa had its
first cases caused by the B.1.617.2 or Delta variant (first identified in
India). At the time, there were five reported cases. By the end of the month,
there were around 22 cases (most in people who had travelled), says Lessells.

The other variant noted by the NICD was the
B.1.1.7 or Alpha variant (first identified in the United Kingdom), which, at
the time, accounted for 11 local cases. Lessells says this has since increased
to 43 genomically confirmed cases, which now includes cases of local
transmission in people who had no history of travel to countries where the
variant was circulating.

Variants 101: Explaining the
different forms of the virus

Variants are versions of the SARS-CoV-2 virus
that have undergone changes, or mutations, in their structure. This is
something that happens to all viruses over time and most of the changes are
insignificant. But in some cases, these small alterations to the genetic code
of the virus can affect how it behaves, such as helping it spread more easily
or causing more severe disease.

The WHO has come up with two categories of
variants that pose a greater public health risk: variants of interest and
variants of concern.

A variant of interest is a version of the virus
which causes community transmission or has been detected in multiple countries.
Variants can also be assigned to this category based on a WHO assessment.

Once the variant has been identified as of
interest, its status can then change to a variant of concern if it is shown to
have increased transmissibility, cause more severe disease, or if it makes
treatments, vaccines or diagnostic tools (tests) less effective.

All three
variants below are variants of concern.

Scientific
names
: B.1.351 or 501Y.V2

First identified: South Africa

Detected
in
: 115 countries

Date
designated as a variant of concern
: 18 December 2020

Earliest
samples
: August 2020

Special
skills
: Ability to spread more efficiently from person
to person and to evade some of the body’s natural defences from previous
infection or vaccination

Initial studies showed the Beta variant was first detectedin October last year in samples from the
Eastern Cape, but Lessells says it has
subsequently been detected in samples as far back as August.

The variant has over 20 changes in its structure
(compared to the original form of the SARS-CoV-2 virus). On its own this is not
cause for concern, but what raised alarm bells was the location of some of
these mutations and their implications for the virus’s structure and function.

The spike protein sits on the surface of the
virus and helps it enter your body’s cells in order to replicate. Changes to
this area, as seen in the Beta variant, allow the coronavirus to better attach
itself to human cells.

The Centre for the Mathematical Modelling of
Infectious Diseases at the London School of Hygiene & Tropical Medicine
estimates that the Beta variant is around 50% more transmissible than its
original form, according to a January preprint study.

In addition to causing more infections, there is
some data showing that the Beta variant is associated with more severe disease
in people who were hospitalised. A May preprint study found that although the
overall death toll during the second wave was not higher, the number of deaths
among patients in the intensive care units increased. This increased severity
in hospitalised patients was also reported in a March preprint.

Another byproduct of the changes to the virus is
that it is better able to outsmart your body’s defences. One of our immune
system’s first lines of attack against infections is antibodies. But mutations
in the Beta variant help the virus to evade antibodies that
previously helped our bodies to fight off the bug.

Scientific
names
: B.1.1.7 or 501Y.V1

First
identified
: United Kingdom

Detected
in
: 161 countries

Date
designated as variant of concern
: 18 December 2020

Earliest
samples
: September 2020

Special
skills
: Ability to spread more efficiently from person
to person

On 14 December, the United Kingdom reported that over 1 000 Covid-19 cases caused by the Alpha variant had been identified in south-east England.
Although the two variants emerged separately, there are commonalities in the
structural changes between Alpha and Beta – particularly in the spike protein.

This version of the virus has 17 mutations – eight of which are located in the spike protein, where the virus attaches itself
to human cells. Because these changes allow the Alpha variant to spread faster from person to person, it is
estimated that it has an increased transmissibility of between 43 to 90%.

A March study published in the British Medical Journal found that the
death toll from Covid-19 cases caused by the Alpha variant had increased from 2.5
to 4.1 deaths per 1 000 detected cases
.This increased mortality rate
was also reported in a paper in Nature
which estimated that the risk of death in cases caused by the Alpha variant was
61% higher than those caused by previous forms of the virus.

People are not at an increased risk of being reinfected with the Alpha variant.
Interestingly, one of the genes deleted in this round of mutations helps make the variant easier to identify in Covid-19 testing
as the area previously targeted in the test is no longer present on the
variant.

Scientific
names
: B.1.617.2

First
identified
: India

Detected
in
: 74 countries

Date
designated as a variant of concern
: 11 May 2021

Earliest
samples
: October 2020

Special
skills
: Ability to spread faster from person to
person, evade immunity

One of the newest to emerge on the list,
scientists are still trying to understand the intricacies of the Delta variant.
But here’s what we know so far:

The Delta variant appears to be spreading faster
than the original form of SARS-CoV-2, although the exact extent to which it is
doing so is unclear. Data from the United Kingdom shows that this variant is
more transmissible than its local counterpart (the Alpha variant), with Delta
having a secondary attack rate (an estimate of how transmissible the virus is)
of 12.4% compared to Alpha’s secondary attack rate of 8.2%.

A May preprint study describes the mutations in
the Delta variant’s spike protein, some of which have also been observed in
other variants. These changes help the virus to better attach to your cells
resulting in it spreading faster from person to person.

Two of the mutations
make it easier for the variant to escape
immunity, rendering the antibodies our bodies produce against the original form
of the virus less able to protect us against the Delta variant.

The UK data from June also shows a slight risk for
increased hospitalisation when compared to the Alpha variant.

What does this mean for vaccines?

Variants which are able to evade immunity could
potentially make vaccines work less well.

In the case of the Beta variant, that has turned out to be true – and there is
some evidence that it may also hold true for the Delta variant.

South Africa has already seen what happens when
vaccines are put to the test against the Beta variant. Both the Johnson
& Johnson
and AstraZeneca vaccine trials took place last
year as the Beta first began circulating. Results from these trials showed how
the jabs offered less protection in a South African context compared to other
countries.

But this is where the baseline of a vaccine’s
protection becomes important.

Just because variants can reduce a jab’s
efficacy doesn’t render it completely pointless. If the starting point for
protection is high enough, then even with the dip in efficacy it is still worth
using.

Lessells says the effect of variants is more
pronounced for mild to moderate disease, and is less so for severe disease,
hospitalisation and death. “This is because protection against severe disease
and death involves other arms of the immune system that are less affected by
the mutations in these variants.”

So in the case of the AstraZeneca vaccine, it
had an efficacy of 62% (against the original form of
SARS-CoV-2) after receiving two doses. But results from the trial in South Africa found
the jab’s efficacy was 21.9% in South Africa (for protection against mild to
moderate Covid-19) – and this further dropped to 10.4% efficacy against cases
caused by the Beta variant.

That means the Beta variant was able to reduce
the vaccine’s efficacy against mild to moderate Covid-19 to the point where it
was considered an inappropriate option for wide-scale roll-out in the country.
(There is no data to show how well the jab protects against severe Covid-19 caused
by the Beta variant).

“That’s what this variant was able to do with
the ChAdOx1 [AstraZeneca’s Covid-19 vaccine] – it just hit it so hard that it
stopped being effective and that’s what you don’t want,” says Alex Sigal, a
faculty member at the Africa Health Research Institute.

As Sigal explains, vaccine efficacy is more of a
hill than a straight line, so variants don’t change the efficacy of all
vaccines in the same way. Instead, you have to see how the efficacy for each
vaccine shifts. In the case of the AstraZeneca jab, the shift was too far and
“pushed it over the edge of the cliff”, according to Sigal, which is why its
efficacy dropped so dramatically.

Sigal explains: “In the end, the solution to
this infection is vaccines. But if the vaccines don’t work, you’ve got a
problem.”

On the other hand, Pfizer’s vaccine – which is
used in South Africa’s vaccine roll-out – seems to have a stronger neutralising
antibody response and is able to withstand the blow dealt by the Beta variant
better. Neutralising antibodies are part of your
immune system’s defence. They attach themselves to the virus in a way that
stops it from infecting your cells.

The pharmaceutical company has reported that its
jab had 100% efficacy against disease caused by the
Beta variant and data from Qatar’s roll-out found that the jab
had an effectiveness of 75% against Covid-19 cases caused by the variant.

Although it is still too early to know if the
same pattern will be seen with the Delta variant, there is some evidence
suggesting that the variant does reduce
vaccine efficacy. Data from cases in England showed that the effectiveness of both the Pfizer and AstraZeneca vaccines
had been lowered
after one dose from 51.1% to 33.5%.

But after a second shot, the decline in efficacy
was smaller. In those who received the AstraZeneca jab, the efficacy had gone
down from 66.1% to 59.8% and those who got the Pfizer vaccine saw a drop from
93.4% to 87.9%.

Since not all jabs are the best choice for all
countries, it is important that vaccines are selected based on which jab can
offer the most protection against the dominant variants circulating in a
country.

“You don’t want to be playing catch up,” says Sigal.

“You’d rather be in a situation where you’re protected from the get go and
that’s antibodies and that means a good vaccine.

“That’s why these variants are
kind of a pain because they can get away from at least some of these vaccines.
So that’s what we need to study, especially if new variants come up that are
worse than the ones we’ve got.”

*This story
was produced by the
Bhekisisa Centre
for Health Journalism
.
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