Omicron can spread even faster than previous Covid variants, but more infections don’t mean people will necessarily get sicker.
Omicron can evade antibodies, which are your body’s first line of defence against germs and stop you from getting infected.
But there’s a more lethal second wave of attack that your immune system launches in the form of T cells – and this can help protect you from falling seriously ill with Covid.
The latest Covid-19 variant, Omicron, will be sticking around for the holiday season. This version of the SARS-CoV-2 virus has undergone a massive transformation — with an incredibly high number of mutations — that allows it to spread faster than any of its predecessors and outsmart at least part of the body’s immune system.
Omicron has quickly begun to dominate infections in South Africa, pushing out its forerunner Delta, which drove the country’s third Covid wave. The latest variant is pushing up case numbers at a rapid pace, with the average number of daily new infections already higher than what they were at the peak of the Delta wave. More infections is one thing, but what that means for how sick we’ll get from Omicron infection is an entirely different ballgame.
Why? Because infection doesn’t always translate into serious disease; our immune systems use many different tricks to outsmart a virus and protect us from falling seriously ill with it.
So far, we’ve seen more infections, but far fewer Covid hospitalisations in the country’s Omicron wave compared to the Delta wave. But that doesn’t by definition mean that Omicron makes people less sick. To know if that’s true, scientists need more time to gather data (because people take time to fall ill) and we also need to consider the protection that vaccination and immunity from previous infection provides.
Some lab studies suggest that Omicron makes our antibodies less effective — but the variant would have to be smarter than that to make large proportions of infected people fall seriously ill because our immune defences consist of much more than antibodies.
In the second and last of our two-part series on what we know so far about what Omicron can and can’t do, we look at the variant’s ability to sidestep our immune systems.
(Find part one here.)
How does your immune system fight off a germ?
When your body is under attack, it mounts a defence. So when a germ enters your body, your immune system gears up to get rid of it. For this, your body uses B cells and T cells.
B cells make antibodies whose job it is to prevent you from getting infected with a germ. Antibodies for each germ look different so they’re able to attack that specific virus or bacterium by destroying or blocking it before it can infiltrate our cells.
T cells kick in once you’ve been infected. Their task is to protect you from falling seriously ill with a germ. Rather than chasing after the invader and catching it before it infects you, T cells kill cells in your body that have already been infected so the uninfected ones have a better chance of survival. So if a germ, for instance SARS-CoV-2, the virus which causes Covid-19, has managed to sidestep your antibodies and penetrate your cells, T cells pick up the mess by sniffing out which cells have been hijacked and getting rid of them. One specific T cell, a CD8, does the killing. That’s why they’re also known as killer T cells. By killing off infected cells, they prevent you from getting sicker.
You also have something called helper T cells, known as CD4s, which help B cells to make antibodies and CD8s to kill germs that invade your body. How do scientists test if a virus can outsmart your antibodies? Finding out if antibodies can fight off a variant means scientists must take the blood from someone who was vaccinated against Covid, previously infected with SARS-CoV-2, or both, and test how well the antibodies in the blood samples stop the variant in its tracks, explains Alex Sigal, a virologist at the Africa Health Research Institute. To do this, blood samples are mixed with the variant and put in a small glass holder called a petri dish to see what happens. When researchers monitor what happens in the petri dish, they’re looking to see how well the antibodies derived from vaccines or natural infection can block the virus. That way, they can find out if a variant can sidestep antibodies, and if so, to what extent. Such studies about Omicron have started to trickle in. On 7 December, South African researchers from the Africa Health Research Institute at the University of KwaZulu-Natal published data from people who had received two shots of Pfizer’s Covid vaccine (so they were fully vaccinated), whose blood got mixed with the Omicron variant. They compared those results with the blood of vaccinated people that got blended with the original form of SARS-CoV-2 that was dominant during our first Covid wave, so that they could work out if Pfizer’s vaccine provides the same amount of protection against both forms of the virus. They also looked at how well Pfizer worked for people who had both been fully vaccinated and who also had antibodies from previous natural infection with a variant other than Omicron (e.g. Beta or Delta). The scientists compared the three groups’ results with each other because when Covid vaccines were designed, they were developed to target the original form of the virus as there were no other variants at the time. The comparison therefore allowed the researchers to see if vaccine-derived antibodies, as well as a combination of the antibodies people developed from infection and those that they produced as a result of vaccination, provided different levels of protection against Omicron and the original form of SARS-CoV-2 and Omicron. Because antibodies protect us against getting infected, such lab tests, called antibody titers, can only tell us how a variant influences our protection against contracting a virus — it can’t tell us how well we’re protected against falling seriously ill with a variant. The results?
A 41-fold drop in how well antibodies from Pfizer’s Covid jab prevent infection and stop the Omicron variant from invading cells (compared to how well they could do this against the form of the virus that dominated South Africa’s first wave). This roughly translates to vaccine efficacy (against infection) of 22.5%, which the study authors caution compromises “the ability of the vaccine to protect against infection”. However, people who had been fully vaccinated and also previously infected, enjoyed higher levels of protection.
Why it’s important to get vaccinated — even if you’ve had Covid before The good news, Sigal, the lead researcher, says, is that Omicron couldn’t completely escape our antibodies. The more antibodies we have, the better our chances are of protection against infection. That is why previous infection, combined with vaccination, increases protection (because it results in more antibodies to deflect the virus). On the up side, although there’s no way to know exactly how many people in South Africa have been infected with SARS-CoV-2, studies have shown that the number of actual Covid cases is likely considerably higher than those reported, so a large proportion of people living in South Africa could have natural immunity. The National Institute for Communicable Diseases (NICD), for instance, estimates that less than 10% of Covid cases are reported, meaning roughly 45% of the country’s population has been infected with SARS-CoV-2 and would have developed antibodies as a result of it, which can provide the added protection that South African researchers showed helped reduce someone’s chances of getting infected with Omicron.
But natural immunity on its own is not enough — studies show that “super immunity” mostly only develops if you’re both fully vaccinated and have natural immunity. Getting Covid after being immunised can also convey this extra layer of protection. That’s why it is important to get vaccinated, even if you’ve had Covid.
In the United Kingdom, early data estimated that there is a three to eight times higher likelihood of being reinfected with the Omicron variant than previous variants like Alpha and Delta.
In South Africa, researchers found that the relative risk of someone who has had Covid, and then got exposed to the SARS-CoV-2 virus again, was close to three times higher to get reinfected if they were exposed to the Omicron variant compared to exposure to the Delta or Beta variants.
A day after the South Africans published their results, Pfizer released their own results of a similar study via a press release. They also found a decrease in protection against Omicron infection, although slightly lower — 25-fold — than Sigal and his colleagues, but Pfizer’s scientists had a similar conclusion: Two doses of Pfizer “may not be sufficient to protect against infection with the Omicron variant”.
This is backed up by real-world data that was released on 14 December by South Africa’s largest medical scheme administrator, Discovery Health. The data, based on the first three weeks of South Africa’s Omicron wave, showed that the protection that two jabs of Pfizer provided against getting infected with the Delta variant in South Africa dropped from 80% to 33% with Omicron.
Pfizer’s research found that receiving a third shot of the vaccine increased protection against infection 25-fold (when compared to two doses). In other words, an extra dose restored the reduced protection of two shots.
With regard to Johnson & Johnson (J&J), the other vaccine that South Africa uses, unpublished data shared by Penny Moore, a virologist at the University of the Witwatersrand, found that in a lab setting, the antibodies generated by the single dose jab dropped to undetectable levels against Omicron.
How do scientists know if a variant reduces our T cell protection? Just because vaccines provide low levels of protection against infection with Omicron, doesn’t mean they don’t help to prevent us from falling seriously ill (their main purpose).
The tests scientists need to do to find out if a vaccine can protect us from severe disease — so if a variant influences how well our T cells can kill already infected cells — are considerably trickier, and also more time-consuming than antibody tests.
T-cell tests, or assays, as scientists call them, involve extracting white blood cells, freezing them (while keeping them alive), exposing the cells to artificially-made pieces of the spike protein of SARS-CoV-2, adding several different chemicals, or reagents, to run different tests and then assembling all the data and analysing it. In short: T-cell assays involve far more than mixing a variant with antibodies contained in blood samples in a petri dish. That’s why, up until now, we’ve mostly only seen antibody test results be released for Omicron. But early data presented to the World Health Organisation, which will soon be published as a preprint, shows that T cell responses from the Pfizer vaccine are holding strong against Omicron. Tests are still being done assessing this aspect of J&J’s jab. In addition, there are T-cell results for previous variants. A November paper in Cell Host and Microbe showed that a single dose of J&J was able to trigger a strong T-cell response against both the Beta and Delta variants. This is why, despite these variants having the ability to outsmart antibodies to some extent, the vaccine was still able to offer high levels of protection against severe disease. What we do have for Omicron, so far, is Discovery Health’s real-world data and also hospitalisation figures from the health department and NICD. Discovery’s data found that although the protection that two shots of Pfizer’s jab provides against hospitalisation with Covid had dropped from 93% with the Delta variant to 70% with Omicron, this is still considerable protection (the WHO considers a Covid vaccine effective when it provides 50% protection). Health department data shows that 19% of new COVID cases in the Delta wave were admitted to hospital in the second and third weeks of the Delta wave, while only 1.7% of cases have been admitted during the same period of the Omicron wave.
What does Omicron mean for the country’s hospitals? NICD data shows an increasing decoupling between new cases and hospitalisations, so while new Covid cases during the Omicron wave are increasing at a much steeper rate than during the Delta wave, hospital admissions are rising at a considerably slower pace. Figures also reveal that patients in our current wave stay in hospital for shorter periods than during the Delta wave, and, when they are hospitalised, a smaller proportion require oxygen or end up in high-care or intensive care units. Moreover, almost everyone who is admitted to health facilities with Omicron is unvaccinated. Scientists don’t yet know if the lower hospitalisation rates are because Omicron causes less severe disease, whether vaccination of particularly older people, who are more vulnerable to falling seriously ill with Covid than younger people, are protecting them, or if it’s a combination of both factors. NICD data, and also Discovery’s real-world data, show that younger people, particularly those below 20 years of age, showed a higher risk of hospital admission than older people during the first few weeks of the Omicron. The NICD, however, reports that in Gauteng, where South Africa’s Omicron outbreak started, that trend is starting to change, particularly with regards to children between the ages of 0-5, with the proportion of admissions of people of 60 years and older now increasing at a faster rate. The picture in provinces where Omicron outbreaks started after Gatueng, is, however, not yet clear and could still be different. But it’s way too soon to tell if this trend will continue as the wave progresses. “It’s too early to be making claims that Omicron causes mild disease — and in fact that’s quite a dangerous message to put out there,” says Richard Lessells, an infectious disease expert and scientist who was one of the scientists who identified Omicron in South Africa.
Covid jabs were designed first to prevent symptomatic disease and not to give you complete protection against getting infected. But preventing illness has become more difficult to achieve as new variants have emerged. So now, the focus has shifted to reducing how serious the illness is after you have been infected, rather than preventing it entirely. The pro of T cells is that they step in when your antibodies need some extra support. So even if your first line of defence doesn’t succeed in fully protecting you, these killer cells come in and fire directly at the already infected cells, helping you keep the illness at bay. Also, part of the body’s immunity has antibodies helping T-cells to kill infected cells. Although we don’t yet have clear data on the extent to which Omicron is able to reduce how efficiently T cells can kill off infected cells, scientists think it’s unlikely that the variant would have much of an effect. One of the reasons researchers believe this is because killer T cells don’t just target one part of the spike protein of the SARS-CoV-2 virus (like antibodies do), so they’re less affected by mutations. “T cells target the whole [spike] protein,” explains Wendy Burgers, a professor of medical virology at the University of Cape Town. “They’re less discriminatory, they go for anything.
So because killer cells strike at hundreds of sites along the spike [where the virus attaches to human cells] as opposed to the more narrow approach of antibodies, they are far less likely to be rendered useless by changes to protein’s structure.” Pfizer’s study found that “as 80% of epitopes in the spike protein recognised by CD8+ T cells are not affected by the mutations in the Omicron variant, two doses may still induce protection against severe disease”. The advantage of this part of the immune response, according to Burgers, is that each person’s genetics influences the T cells attack formation. “When it comes to T cells, unlike with antibodies, it is unlikely that there will be a population effect,” she says. This means, according to Burgers, that even if the T-cell response does take a knock in some people, it’s not going to affect everyone in the same way (as happens with antibodies). So while antibody evasion means that some protection is lost in everyone, outmanoeuvring killer cells will only happen in some people. Burgers explains: “It's likely that a proportion of people may be affected and lose some of their immune response from these mutations — but what is left may be enough of a T-cell response to still protect [the population at large] from severe disease and death.”
So how protected from Omicron are you?
Early lab data shows Pfizer vaccination doesn’t provide much protection against infection, but that a third booster shot could potentially increase protection against infection.
Looking at Pfizer and AstraZeneca’s jabs, there is a sharp drop protection against mild Covid. People with two shots of AstraZeneca’s jab have almost no defences against developing symptomatic Covid disease.
While Pfizer’s vaccine efficacy against Covid has dropped from over 90% for previous variants to around 30% for Omicron at 15 weeks post-vaccination, this protection rises again to 92% in those who have gotten a third dose.
But we don’t yet know for how long the protection that a booster shot might provide against getting infected with SARS-CoV-2, would last, as vaccine-derived immunity has been shown to wane over time.
But booster shots’ protection against falling seriously ill with Covid, would be less affected by waning immunity, because B cells, which produce antibodies, also come in the form of memory cells, whose job it is to produce additional antibodies when they come across a familiar foe. And where the number of antibodies people produce may decrease from about six months after vaccination, memory cells usually stick around for longer.
An October paper in Science found that memory B cells triggered by mRNA vaccines (Pfizer is an mRNA vaccine) increased six months after people had been fully immunised. This protection also held strong for the Alpha, Beta and Delta variants of the virus.
We also have real-world data, in the form of Discovery Health’s study and also the hospital and infection data that the NICD collects, that show that two Prizer jabs likely provide considerable protection against falling seriously ill with Omicron infection.
But since South Africa is only three to four weeks into its Omicron wave, and there is, so far, also little data available from other countries, it’s simply too early to tell, for sure, what impact Omicron will have on severe disease.
Lessells concludes: “Because to actually answer the question [of disease severity and vaccine protection] requires more time, more data, and very careful data analysis to really understand what we're seeing.”
By Aisha Abdool Karim
https://www.news24.com/health24/medical/infectious-diseases/coronavirus/covid-19-the-secret-is-in-your-cells-how-the-body-can-protect-you-from-getting-sick-with-omicron-20211220
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