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The question about how Covid-19 vaccines stand up to coronavirus variants often gets distilled to: Do they work?

The simplest answer is yes. People who’ve received one of the highly powerful vaccines don’t need to be too worried about the variants for now, experts say.

But the complete answer is more complicated.

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The real question isn’t whether the vaccines work, but how well they do. Even the best vaccines allow some “breakthrough infections” — infections in people who’ve been immunized. And there are outstanding questions about how the continued emergence of variants — such as the one that’s popped up in India and appears to be helping fuel the explosion in cases there — will shape the Covid-19 pandemic into the future and potentially affect vaccine strategies.

It’s also helpful to specify what you’re talking about. Different countries are deploying different vaccines, and different variants have different tricks up their genetic codes. Clinical trials generally measured how well the vaccines prevented symptomatic Covid-19, but just as relevant are such questions as, how well do the vaccines protect against severe disease, hospitalization, and death? Do they block infections entirely, even those without symptoms? And even if people still contract the virus, does being immunized make them less infectious?

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“There’s no simple, one-line sound bite,” said John Moore, a professor of microbiology and immunology at Weill Cornell Medical College.

Below, STAT outlines the latest on some of the vaccines’ performance against the variants, what’s known about the variant of concern in India, and how the continued emergence of variants will shape the future of Covid-19.

The variants and vaccines

Two variants have raised the most concern in terms of evading immunity: B.1.351 and P.1, which were first identified in South Africa and Brazil, respectively, and which share some of the same genetic changes that partially cloak the viruses from the immune system’s fighters.

In clinical trials, some of the vaccines lost efficacy against B.1.351, though certain trials also showed the immunizations could provide enough protection to generally guard against severe disease. (It’s typically easier for vaccines to prevent the worst outcomes of an infection than to prevent mild cases or block infection entirely.)

B.1.351 and some of its mutations also showed in lab experiments some ability to “escape” the antibodies generated by vaccines that are found in the blood, or serum, of people who’d been immunized. Experts cautioned, however, that what could be gleaned from those studies was limited, both because they only examined one aspect of the body’s broad immune response and because the vaccines elicit such strong antibody responses that people can afford to lose some of that potency without reverting to a sitting-duck state.

“They give people a huge amount of antibody, so even if you have a fivefold reduction in reactivity in your serum to some of these variants, you’re still left with a bunch of antibodies that can bind and block” the virus, said Richard Webby, an infectious disease expert at St. Jude Children’s Research Hospital, citing the mRNA vaccines in particular.

Since then, real-world studies with some of the vaccines have backed up those findings, indicating that while B.1.351 may cause more breakthrough infections than other forms of the virus, the vaccines are still widely protecting people from it, including most powerfully against serious disease and death.

A study out of Israel, which has used the two-dose Pfizer vaccine, found that B.1.351 was the culprit behind a higher rate of breakthrough infections, indicating it was skating past immune protection more frequently than other forms of the coronavirus. The number of those infections, however, was low, and Israel has managed to greatly suppress its Covid-19 epidemic through widespread vaccination.

Another study last week out of Qatar, which has also used the Pfizer vaccine, estimated the effectiveness of the vaccine against any B.1.351 infection was about 75% — a strong result, if a drop from its performance in clinical trials before the emergence of B.1.351. Overall, however, the vaccine was 97.4% effective against severe, critical, or fatal disease caused by any variant that was circulating in the country, including B.1.351. “The reduced protection against infection with the B.1.351 variant did not seem to translate into poor protection against the most severe forms of infection,” the researchers wrote.

Studies indicate P.1 has roughly the same or even less ability to evade immunity as B.1.351, giving researchers confidence that the vaccines can generally stand up to that variant as well. A rapid and broad deployment of initial vaccine doses, combined with enhanced restrictions on businesses, is credited with helping quell a P.1-driven outbreak this spring in British Columbia.

“There’s a degree of reduction of efficacy, but it’s going to be manageable” with the high-performing vaccines, Moore said. “It’s why we call these ‘variants of concern,’ and not ‘variants of mass panic.’”

While most of the attention in terms of vaccine effects has focused on B.1.351 and P.1, sometimes nonevents are worth noting as well. The other variant of concern is B.1.1.7, which emerged in the United Kingdom and is not only much more transmissible than other forms of the virus, but also causes severe disease at higher rates. The vaccines, however, are continuing to work exceptionally well against the variant, both protecting individual people and snuffing out transmission, which helps explain why case counts are tumbling now in the United States, even as B.1.1.7 has become dominant.

“It is clear that [B.1.1.7] is not an antibody-resistant virus,” Moore said.

Another variant of concern enters the arena

Another variant entirely, called B.1.617, appears to be helping fuel India’s devastating spring Covid-19 surge. And if the alphabet soup of different variant and mutation names wasn’t already causing enough headaches, there are different sublineages of the variant that have their own characteristics.

One of the subtypes is somewhat resistant to vaccine-elicited antibodies, though perhaps not to the same extent as B.1.351, according to two preprinted studies. Such concerns, along with some evidence that B.1.617 is more transmissible, led the World Health Organization this week to designate it as a variant of concern.

But the authors of those studies also found that the level of immunity generated should still be broadly protective against the most serious outcomes. As researchers wrote in one, “extensive vaccination will likely protect against moderate to severe disease and will reduce transmission of B.1.617,” if perhaps not as quickly as it would suppress other, less threatening variants. (More transmissible variants require a higher percentage of people to be protected before their circulation tapers off.)

“There are a number of reports from India saying that although there’s infection in people who’ve been vaccinated, there is protection against severe disease,” said Ravi Gupta, the senior author of the paper and a professor of clinical microbiology at the University of Cambridge. “So on an individual level, vaccination is still fantastic and works. But in terms of controlling transmission, there may be a degree of compromise.”

Separately, researchers are still trying to confirm whether B.1.617 (or its subtypes) is indeed more transmissible than earlier forms of the virus, and if it is, how it compares to something like B.1.1.7. The variant has taken off in India, but its ascendance coincided with a rollback in mitigation efforts and the snowballing prevalence of outbreak-driving B.1.1.7.

B.1.617 “did not cause the entire situation we’re seeing in India,” said infectious disease expert Kristian Andersen of Scripps Research Institute. “It might well add it to it. Does it play a 5% role? Does it play a 70% role? I don’t know.”

What it means going forward

The particulars of variants — whether those already on the world’s radar, or the ones that could appear if the virus continues to transmit — will shape the future of the Covid-19 pandemic, which is why it’s crucial for scientists and public health authorities to keep up with them.

“Should an individual who is vaccinated be concerned about being infected by something like P.1 in the short term and getting sick from it?” Andersen said. “The answer to that is no. The vaccines remain highly effective when it comes to these variants. The question is, what might we expect a year from now?”

Some scientists think that people eventually will need vaccine boosters, and that the vaccines might need to be tweaked to better match the evolving virus. Among the questions that will influence when and how that might occur: How long does vaccine-generated protection last, and will the waning process accelerate in the presence of certain variants? If immunity starts to wane, will people still generally be protected from the worst outcomes, even if they’re more vulnerable to infection?

While those questions can’t be answered yet, work is in progress to prepare for the possibility of boosters. Vaccine makers, for example, are testing refined recipes for their shots. Moderna last week unveiled data showing a booster bolstered antibody levels against B.1.351 and P.1, and that another booster designed specifically against B.1.351 elicited even stronger defenses.

There’s some evidence that even a booster of the existing vaccines might be enough to handle variants should an extra shot become necessary. A preprint study published this week found that people who recovered from Covid-19 and then received an mRNA vaccine had long-lasting and broad immunity against the coronavirus and its variants. An extra shot could act like that additional exposure, the researchers suggested, writing that such a strategy “could cover most circulating variants of concern.”

“Depending potentially on the vaccination protocol, the vaccines are good enough to deal” with B.1.351 and other variants, said virologist Theodora Hatziioannou of Rockefeller University, an author of the study. “At least,” she added, “the variants we’ve seen up to now.” 

The unknown future of the virus and its evolution means that scientists will continue to be on the lookout for variants that could throw a wrench in the global response, said Sharon Peacock, the executive director of the Covid-19 Genomics UK Consortium.

“This is something that we’re just going to need to keep doing for the foreseeable future.”

  • “…given the high cycle PCR testing, we have a ton of false positives out there.”

    The cycle threshold value of the PCR tests became the rallying cry of Berenson, Ethical Skeptic, Ivor Cummins, Gato Malo and their respective acolytes. It purported to explain the emergence of the so-called “casedemic.” Nonetheless, I remain unconvinced. Here’s an article from an Australian virologist that casts significant doubt on the notion of the false positive “problem” (or lack thereof). I’d be curious to know your reaction:

    https://virologydownunder.com/the-false-positive-pcr-problem-is-not-a-problem/

  • 30M infections have led to where we are. There are something like 160M unprotected Americans out there. Also, consider that a significant proportion of immunized individuals are people who were already staying home and being cautious. Thankfully the warm weather should help now. But the infections will continue because half the population remains susceptible.
    Sadly the anti-vaxers may feel they can “handle it” but they should be more concerned with the cost to society by being spreaders and the continued strain on healthcare workers.

    • KM, first of all not everyone who is or becomes infected is a “spreader.” As a doctor, you should know that. A few people shed a lot of virus; some don’t shed any.

      Second of all, I think the 160M number is hyperbolic. There are naturally immune unvaccinated people out there who will never get the virus, even if they are exposed to it. Meanwhile, it doesn’t matter if EVERYONE is vaccinated–we simply have to have ENOUGH people vaccinated so that, given already infected and naturally immune/unsusceptible people, the virus and its variants have nowhere to go.

      Third infections are not the right metric — given the high cycle PCR testing, we have a ton of false positives out there.

      Fourth, it probably feels good to demonize the anti-vaxxers, but you know what? We have a free country and compelling people to take medicine is arguably coercive and fascistic. Besides, they’re a minority anyway–though, as someone who HAS been vaccinated, I’ll say that if the anti-vaxxers get sick and die from the virus I am not going to lose sleep over it.

      Fifth, and finally, if vaccinated people are STILL hunkering down in fear about this thing, they have begun to fetishize their fear and uncontrolled risk aversion. Our public health “experts” like that short Italian bureaucrat with the Napoleon complex, certainly haven’t helped matters in this regard.

      Then again, in his effort to be a vaccine hero during the AIDs crisis, the aforementioned bureaucrat arguably contributed to the death of thousand by ignoring therapeutics — and maybe, just maybe, he is directly or indirectly complicit in gain-of-function research that maybe, just maybe, is the root cause of this entire catastrophe.

    • KarlPK, there is no such thing as natural immunity to a virus your body has never encountered before. Immunity only develops from contact and response. The fact that you don’t even understand how the immune system works makes your entire argument here essentially worthless.

    • Exactly. People who don’t get vaccinated don’t understand that they hold a piece of the puzzle that will only get us past this pandemic when it is assembled. As a musician who’s been mostly out of work since March 2020, I have little patience for people exercising their freedom to stretch this pandemic out a day longer than it has to run by not getting vaccinated.

  • The lockdowns and hysteria are killing the Democrats in their internal polling. From here on out everything will work against the virus. That is until another crisis is needed to ward off political disaster. At that point we’ll have our crusade against no covid vaxxers.

  • Didn’t learn much from the article as most of this info has been widely available. Would have liked to see some comment about the possible benefit of cross vaccination to enhance both humoral immunity (M-RNA vaccines – Pfizer) and cellular immunity (viral vector vaccines – J&J).

  • Good piece Andrew.

    What wasn’t addressed is that the combination of vaccines and recovered infections will inevitably limit the number of places any specific variant can go, as well as the extent to which such infections are severe if they do occur, and thus will dampen the possibility of any re-triggered widespread pandemic from any variant. Alas, some people will get sick and some people will succumb, but both the virus and its variants will inevitably peter out, as all viruses do.

    India is the unlucky outlier and exception to this rule, but many other factors came into play there. The limited vaccination efforts, and even more important, the high levels of poverty, poor sanitation, and dense population centers, made India a petri dish for the outbreak that is occurring.

    The gleaming towers of Mumbai hide a fundamental fact about India—it is third world country in many respects, where health care quality is low, and, as such, the country is very unprepared to handle a huge outbreak. I also haven’t seen any race related data on infections – for example are Dravidians more likely to acquire the infection?

    I guess we’ll see more data as time goes on.

  • I very much appreciate this article. Many thanks to the author and STAT.
    But this brings up a lot of questions – the STAT email shows over 800 deaths yesterday- if the vaccines are already stopping the variants we have here – that is, we can not stop those deaths by tweaking the vaccines to be more effective against variants – does that mean 800 deaths per day is the new normal?
    Also, the data available online indicate increases in daily cases even after 30 to 40% of population got fully vaccinated. Small increases for sure- but where I live, in public at least, prophylactic rules are followed about as they were before – yet with half the people fully vaccinated, and an outbreak just 4 months back, cases still go up? How can that be possible? I blamed it on variants, and, as a proportion of cases, P1 is increasing rapidly, but not enough to drive the rise in the curve by itself. ????

    • Steve, I think a lot of the data is — and, frankly, has been — very noisy.

      I know some folks have stupidly said the virus isn’t real because the say, well, “See the discrepancy between people who died OF Covid and WITH Covid? The real death number is “from Covid” and is WAY lower!!”

      Well, no, that’s too big of a leap. But on the other hand there IS an issue with this distinction, and should be taken into account. Most victims skew older, many of who have end of life inflammatory conditions. The average number of serious co-morbidities in all deaths is close to 4. That’s a high number.

      So bottom line, I would say it’s a temporary new normal, which will decline to some lower new normal as time passes. Vulnerable people remain vulnerable, but certainly less vulnerable as time goes on.

      Your point about the disconnect between prophylactic measures and the bad data is telling — frankly, lockdowns, mask wearing, social distancing — all the usual suspects — just don’t make much difference, because most people are generally healthy and either won’t get infected or can handle it. And only a fraction of those infected are “super spreading” shedders. Moreover, some people are just ripe for infection, no matter what we do.

      Life is tragic.

      As for the infection rate, well, those numbers have always been squirrely, perhaps approaching meaninglessness, given the high PCR cycles used, and the level of both false positives and negatives.

      Truly understanding a pandemic requires a deep multifactorial analysis of many dozens of variables, sometimes conflicting, that, frankly, we are not equipped to assess. As a result, predictive models are flawed, and post hoc analyses are crude. The unconscious unthinking virus will eventually lose the war, but it will be victorious in specific battles — e.g., showing how “experts” who are presumably conscious are just not up to the analytical task.

    • Steve, the pandemic is not over yet, and may never be. The percentage of smart ones getting vaccinated is increasing, but the variants are getting stronger, Covid kills are now increasing in younger people, and there are too many simpletons who do not “believe” in vaccination or masks etc. Thus – there will be Covid deaths until more people are vaccinated, and more people shape up. Only then will numbers go down as then ever-changing variants are rendered less effective.

    • KarlPK:

      “As for the infection rate, well, those numbers have always been squirrely, perhaps approaching meaninglessness, given the high PCR cycles used, and the level of both false positives and negatives.”

      The cycle threshold value of the PCR tests became the rallying cry of Berenson, Ethical Skeptic, Ivor Cummins, Gato Malo and their respective acolytes. It purported to explain the emergence of the so-called “casedemic.” Nonetheless, I remain unconvinced. Here’s an article from an Australian virologist that casts significant doubt on the notion of the false positive non-problem. I’d be curious to know your reaction:

      https://virologydownunder.com/the-false-positive-pcr-problem-is-not-a-problem/

  • Qué opinan de realizar los estudios serológicos para evaluar seroconversión frente a la vacuna (detección de anticuerpos neuntralizantes para el antígeno S), si aún desconoce cual es el mínimo de seroconversión para “asegurar” protección por la vacunación.

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