KINIGUIDE | Symptoms, vaccines and what's new with Omicron
KINIGUIDE | In yesterday’s KiniGuide, we looked at the Omicron variant situation in Malaysia and how the government responded to the new threat.
A large part of the government response is to ramp up Covid-19 booster shots. As of Sunday, 78.6 percent of Malaysia’s population is fully vaccinated, of which 28.7 percent have also received a booster shot.
Progress in primary vaccinations has stagnated for months now as most eligible people have received their shots. A few thousand doses are administered per day.
Meanwhile, an average of more than 210,000 booster doses are administered per day.
But these vaccines were developed based on the Covid-19 strain that was first isolated in Wuhan, China in January 2020, and the millions of infections worldwide provided ample opportunities for an otherwise slow-evolving virus to mutate.
In this second KiniGuide of a two-part series, we look at how well current Covid-19 vaccines and tests are holding up against the new variant and wrap up with what else we have learnt about it so far.
Do vaccines still work?
Broadly speaking, yes; even though data on this subject is still emerging. However, there are also early signs that the current strategy of countering each new variant with additional doses of vaccines based on the original Wuhan strain is being stretched to its limit.
The good news is that vaccine effectiveness against hospitalisation, severe illness and death remain robust, even though it has been reduced compared to earlier variants. This is supported by data from the UK, Denmark, South Africa, and other countries.
As mentioned in yesterday’s guide, Omicron’s reduced severity in South Africa is mostly attributed to immunity through prior infection or vaccination, though 25 percent of that reduced severity is probably due to changes in the virus itself.
The UK Health Security Agency (UKHSA), for example, found that even a single vaccine dose reduced the risk of hospitalisation by about 52 percent, while the second dose raises this to around 64 percent.
The effect wanes over time, down to 44 percent after six months.
However, a booster shot can increase this to more than 80 percent. It is not yet clear how long this protection will last since the booster rollout is a relatively recent development, but it has lasted at least two-and-half months so far and will likely hold for much longer.
KINIGUIDE | In yesterday’s KiniGuide, we looked at the Omicron variant situation in Malaysia and how the government responded to the new threat.
A large part of the government response is to ramp up Covid-19 booster shots. As of Sunday, 78.6 percent of Malaysia’s population is fully vaccinated, of which 28.7 percent have also received a booster shot.
Progress in primary vaccinations has stagnated for months now as most eligible people have received their shots. A few thousand doses are administered per day.
Meanwhile, an average of more than 210,000 booster doses are administered per day.
But these vaccines were developed based on the Covid-19 strain that was first isolated in Wuhan, China in January 2020, and the millions of infections worldwide provided ample opportunities for an otherwise slow-evolving virus to mutate.
In this second KiniGuide of a two-part series, we look at how well current Covid-19 vaccines and tests are holding up against the new variant and wrap up with what else we have learnt about it so far.
Do vaccines still work?
Broadly speaking, yes; even though data on this subject is still emerging. However, there are also early signs that the current strategy of countering each new variant with additional doses of vaccines based on the original Wuhan strain is being stretched to its limit.
The good news is that vaccine effectiveness against hospitalisation, severe illness and death remain robust, even though it has been reduced compared to earlier variants. This is supported by data from the UK, Denmark, South Africa, and other countries.
As mentioned in yesterday’s guide, Omicron’s reduced severity in South Africa is mostly attributed to immunity through prior infection or vaccination, though 25 percent of that reduced severity is probably due to changes in the virus itself.
The UK Health Security Agency (UKHSA), for example, found that even a single vaccine dose reduced the risk of hospitalisation by about 52 percent, while the second dose raises this to around 64 percent.
The effect wanes over time, down to 44 percent after six months.
However, a booster shot can increase this to more than 80 percent. It is not yet clear how long this protection will last since the booster rollout is a relatively recent development, but it has lasted at least two-and-half months so far and will likely hold for much longer.
The bad news is that vaccine protection against milder infection - and thus onward transmission of the disease - proved to be more fickle.
The protection is much diminished compared to the protection available against the Delta variant. A booster shot can restore most of the lost protection, but even then, protection declines more steeply compared to the Delta variant.
The UKHSA found two doses of the AstraZeneca vaccine initially had 45 to 50 percent effectiveness against symptomatic infection with the Omicron variant but had “almost no effect” after 20 weeks following the second dose. The Pfizer vaccine, meanwhile, dropped from around 20 percent to 10 percent over the same period.
A booster dose using an mRNA (Pfizer or Moderna) vaccine initially raises effectiveness against symptomatic infection to around 65 to 75 percent, but this falls to 55 to 65 percent in the second month after the booster shot and 45 to 50 percent after two-and-half months.
This is even as protection against the Delta variant remained high during this period.
For comparison, the World Health Organization (WHO) states that Covid-19 vaccines must be more than 50 percent efficacious against symptomatic infections - at least in idealised conditions of a clinical trial rather than in the real world - in order to be approved for use.
Meanwhile, vaccines appear to reduce the risk of onward transmission of the disease after becoming infected.
A study in Denmark found that when an unvaccinated person is infected with the Omicron or Delta variant, the odds of it being passed onto a household member is 41 percent higher compared to a vaccinated index case. A booster dose reduces the odds by 28 percent compared to those with only two doses.
It found no difference in this regard between the Omicron and Delta variants, though it did find that the Omicron variant will infect a larger proportion of household members.
What about AstraZeneca and Sinovac boosters?
As of the time of writing, the author of this KiniGuide is unable to locate any real-world data for the Sinovac vaccine (primary series and booster) and AstraZeneca vaccine (booster) against Omicron.
Instead, only laboratory studies are available. These broadly fall into two categories: studies on neutralising antibodies and studies on cellular immunity such as “killer” T-cells.
Neutralising antibodies can act early in the early phase of an infection by physically blocking key parts of the virus and preventing it from infecting human cells.
High levels of neutralising antibodies are associated with lower risks of a breakthrough infection but less indicative of protection against more severe manifestations of Covid-19.
T-cells are a different part of the immune system that generally respond in later phases of infection. They destroy cells that have already been infected and help keep the infection from progressing into severe disease.
They are more resilient to mutations in a pathogen (including the Omicron variant) and fade more slowly over time. In other words, they can mount a defence against Covid-19 even when antibodies fail.
However, they are more difficult to study than antibodies so there are fewer reports about them.
So far, Sinovac claimed its booster shot could elicit antibodies that neutralise the Omicron variant, but researchers at Hong Kong University found the antibody levels are still too low after the third Sinovac dose.
They recommended the Pfizer booster for Sinovac recipients instead after finding it produced antibody levels above a “protective threshold”, though still lower than those elicited through three doses of the Pfizer vaccine.
Researchers at Yale University and the Dominican Republic’s Health Ministry made similar findings regarding a two-dose course of Sinovac vaccine and a two-dose course followed by a Pfizer booster, but one of its researchers argued even this was not enough, and a fourth dose might be necessary.
In a press release, Sinovac’s Malaysia distributor Pharmaniaga quoted preliminary findings of a study at Pontifical Catholic University, Chile, saying that a Sinovac booster can activate T-cell responses at similar levels as it did with the original Wuhan strain.
Meanwhile, WHO incident manager Abdi Mahamud predicted that T-cell immunity would mean Sinovac and Sinopharm vaccines would retain protection against severe hospitalisation (ie intensive care unit admission and mechanical ventilation) and death against the Omicron variant.
As for AstraZeneca, the company said the third dose of its vaccine boosted antibody levels against the Omicron variant. It has published its findings as a pre-print and said it would submit the data to regulators.
All that being said, the way antibodies, T-cells, and other parts of the immune system come together to provide protection against Covid-19 of any variant is not fully understood, at least not at a level that would allow us to predict how effective vaccines might be against a given variant from laboratory tests alone.
Research on these “correlates of protection” is ongoing. Until then, it would be important to monitor how well vaccines are faring in the real world.
I've just received my third dose, do I need the fourth one already?
Although some countries such as Israel have started offering fourth vaccine doses to high-risk groups, the actual need for such a move is not yet clear at this time.
The UKHSA said there is no need for now because booster doses still offer high levels of protection for older people against severe disease.
Pfizer chief scientist Mikael Dolsten reportedly said in early December last year that a fourth dose is likely needed within months if Omicron persists as the dominant variant, as did its rival Moderna’s CEO Stephen Bancel last week.
However, Pfizer’s CEO Albert Bourla said he is unsure, and the need for the fourth dose still needs to be tested.
Meanwhile in Malaysia, Health Minister Khairy Jamaluddin said his ministry is looking into the need for an additional booster for Sinovac vaccine recipients, following the report from the Dominican Republic.
As for the WHO, a technical committee advising on vaccine composition said the strategy of repeatedly using booster doses of current vaccines is unlikely to be sustainable and called for new vaccines that offer broader, longer-lasting protection.
It laid out three different strategies to achieve this. The first is a newly formulated vaccine that targets the most prevalent variant, which is the Omicron variant at the moment.
Soon after the emergence of the Omicron variant, several pharmaceutical companies have started work on an Omicron-specific vaccine, with Pfizer indicating theirs would be ready in March.
Variant-specific Covid-19 vaccines had been trialled before, especially against the Beta variant.
Before the arrival of the Omicron variant, Beta was the variant that was most capable of evading immune responses elicited by current vaccines.
However, Beta-specific vaccines were never used outside of clinical trials, and the variant has already faded into obscurity after being overtaken by the faster spreading Delta variant last year.
The second strategy is a multivalent vaccine formulated based on several Covid-19 variants.
This approach is similar to annual influenza vaccines – each dose contains several influenza strains that are most likely to become prevalent in upcoming flu seasons.
The third approach is to develop a vaccine that can protect against any Covid-19 variant and is essentially variant-proof. Such a vaccine would take advantage of the fact that the virus that causes Covid-19 mutates more slowly than many other viruses and has fewer tricks to evade the immune system.
The search for a pancoronavirus vaccine - which not only protects against Covid-19 but also other coronaviruses - is already underway.
This development is spurred by the discovery of antibodies that can neutralise multiple Covid-19 variants in addition to the SARS-CoV virus behind the 2002 epidemic and promising animal studies.
Do Covid-19 tests still work?
For PCR tests, yes, and with a quirk that can help us keep track of the Omicron variant.
PCR tests work by detecting the presence of certain genetic signatures present on the virus that causes Covid-19, and some PCR test kits use the virus’ S-gene as a target.
Omicron almost always has a mutation that causes this part of the test to fail, and the phenomenon is known as S-gene target failure (SGTF).
However, PCR tests are designed with mutations in mind, so each test would target several different parts of the virus’ genome and will still pick up on the virus if one or two of these targets mutate.
The Alpha variant also has this mutation that causes SGTF, as do some lineages of the Delta variant. Moreover, there are rare instances where this mutation is not present on the Omicron variant.
Given the rarity of these outliers, however, SGTF is still a good indicator for the presence of the Omicron variant. Many health authorities, including Malaysia, would consider a positive PCR test result with SGTF to be a presumptive Omicron variant case.
This approach has the advantage of being much cheaper than whole-genome sequencing and can yield results within hours instead of weeks.
A related concept is PCR genotyping, which uses a PCR test specifically designed to detect the presence or absence of multiple tell-tale mutations. These can be used to infer the Covid-19 variant involved more precisely and carries similar advantages of PCR-based tests compared to the gold-standard whole-genome sequencing.
The picture is more mixed for rapid antigen tests (RTK-Ag). Some reports such as those from the US Food and Drug Administration said such tests may have reduced sensitivity with the Omicron variant even though it can still detect the virus.
Most concerningly, a small US study found some participants had false-negative RTK-Ag results for several days before finally detecting the infection, even though the viral load inferred through daily PCR tests was high enough to be infectious.
In at least four out of the 30 cases studied, the disease was unwittingly spread to others in between false-negative results from daily RTK-Ag tests.
Initial laboratory testing by the UKHSA, however, found that RTK-Ag tests were not affected by the Omicron variant’s mutations, as did Denmark’s Statens Serum Institute.
A WHO report said it is still assessing Omicron’s impact on diagnostic devices, including RTK-Ag tests.
On a related note, the aforementioned US study and several others also found that the amount of virus present in saliva and throat samples reaches a peak sooner than in samples taken through the nose, hinting that tests on the former may be more sensitive.
What else is different about Omicron?
A close contact of an Omicron-infected person may become infectious himself in about two days after exposure, according to an analysis of a Covid-19 cluster in South Korea, compared to three days for the Delta variant.
The UKHSA disagreed, reporting that its contact tracing data found little difference between Omicron and Delta. However, it conceded its methods could underestimate such differences.
In a separate analysis, the UKHSA found 15.8 percent of Omicron variant household close contact cases are becoming infected, compared to 10.3 percent for the Delta variant.
In terms of symptoms, the UKHSA found sore throats to be more prevalent in Delta variant cases than Omicron variant cases, while reports of loss of smell or taste have sharply declined.
Meanwhile, the UK-based Zoe Covid-19 symptom tracking study found that the top five symptoms for both Omicron and Delta are runny nose, headache, mild-to-severe fatigue, sneezing, and sore throats.
“This analysis found no clear difference in the symptom profile of Delta and Omicron, with only 50 percent of people experiencing the classic three symptoms of fever, cough, or loss of sense of smell or taste,” it said.
However, coughing was the top symptom in the analysis of an Omicron outbreak at a Christmas party in Norway involving fully vaccinated (but not boosted) attendees.
Nearly all infected attendees had symptoms, 83 percent of whom reported coughs and 78 percent had a runny or stuffy nose. Fever was reported in 54 percent of attendees, reduced sense of taste in 23 percent, and reduced smell in 12 percent.
A leading hypothesis that may explain Omicron’s higher transmissibility and reduced severity comes from several animal and petri dish studies, suggesting that the virus replicates itself much better in the airways compared to the Delta variant but worse in the lungs.
It is proposed that this helps the virus aerosolise and spread better as we speak and breathe, leading some experts to call for cloth masks to be abandoned in favour of double-masking (wearing a cloth mask over a surgical mask to improve the fit of the latter) or respirators such as N95 and KF94 that are designed to provide a tight seal against the face.
At the same time, Omicron’s relatively weak attack on the lungs is putting a smaller percentage of them in hospitals compared to the Delta variant.
What about 'Flurona' and 'Deltacron'?
'Flurona' colloquially refers to a person being simultaneously infected with both Covid-19 and influenza. This has happened throughout the pandemic even though the word was only coined or popularised last month.
According to WHO technical lead on Covid-19 Maria Van Kerkhove, studies have found that such co-infections do not lead to more severe disease, but it remains to be seen if things will be different with the Omicron variant.
As for 'Deltacron', expert consensus is that the finding is a result of contamination during the sequencing process and is not real, even though its discoverer in Cyprus has stood by his findings.
“This phrase 'Deltacron', which suggests that Delta and Omicron have combined, is not really a thing… Having said that, you can be infected with different strains of SARS-CoV-2,” Van Kerkhove said.
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