More Vaccine-Resistant, Contagious, and Lethal Coronavirus Mutant: How Bad is the Situation?
After looking at the data, the situation isn’t good, but it’s not catastrophic (yet).
If you have been keeping up with coronavirus development, you’d probably know that things are getting worse. Last week, it was announced that Covid-19 mRNA vaccines are less effective against the U.K. and South Africa SARS-CoV-2 mutants. Preliminary data from the U.K. also shows that the mutant is 30–40% deadlier and 30–70% more transmissible. This article will look at what these numbers really mean in context.
The mutant in the U.K. is called B.1.1.7, N501Y, or 501Y.V1. The one in South Africa is B.1.351, E484K, or 501Y.V2. The one in Brazil is B1.1.28 or 501.V3. The one in Southern California is CAL.20C. Since they go by various names, I’ll just refer them by the country it was first discovered in. Only the U.K. and South Africa mutants will be discussed herein since there’s not much data about the others.
Less effective vaccines?
Thus far, at least three studies — released as preprints from well-respected researchers and institutions — have investigated how the current mRNA vaccines fare against the mutants.
- In one study, researchers at Rockefeller University, New York, took blood samples from persons vaccinated with either the Moderna’s or Pfizer-BioNTech mRNA vaccines. Although these persons had high levels of antibodies against the original SARS-CoV-2, the antibodies were up to 3-fold less efficient at neutralizing the South African and U.K. mutants.
- Another preprint from Pfizer-BioNTech did similar research in testing the antibody efficacy of vaccinated persons against the U.K. mutant. Results showed that the mRNA-induced antibodies were equally effective at neutralizing the original SARS-CoV-2 and U.K. mutant.
- A preprint from Moderna and the National Institute of Allergy and Infectious Diseases also performed similar experiments. Antibodies sampled from vaccinated persons’ blood were highly potent at neutralizing the original SARS-CoV-2 and U.K. mutant. But, “A six-fold reduction in neutralizing titers was observed with the B.1.351 [South African] variant relative to prior variants,” Moderna said in a press release. “Despite this reduction, neutralizing titer levels with B.1.351 remain above levels that are expected to be protective.”
Synthesizing these preprints, one found evidence of vaccine resistance with the U.K mutant, but two reports found the contrary. Only two studies studied the South African mutant, and both reported evidence of vaccine resistance — showing up to a 3- and 6-fold decrease in antibody neutralizing efficacy.
Indeed, the South African mutant has been deemed the ‘most worrying’ of all due to its E484K mutation that helps the virus escape antibodies.
This means that the mRNA vaccine-induced antibodies were less efficacious against the South African mutant, but it gets the job done.
But, to repeat Moderna’s statement, “Despite this reduction, neutralizing titer levels with B.1.351 remain above levels that are expected to be protective.” Indeed, it’s stated in the study results section that, “Despite diminished neutralizing responses against the B.1.351 [South African] variant, neutralizing titers remain generally high…, and all sera samples completely neutralized the [coronavirus mutant].” This means that the mRNA vaccine-induced antibodies were less efficacious against the South African mutant, but it gets the job done.
“The mRNA vaccines, in particular, induce such a strong NAb [neutralizing antibody] response that there could be enough “spare capacity” to deal with reductions in the sensitivity of the variant to NAbs,” explained a viewpoint in the Journal of the American Medical Association (JAMA). “In other words, N501Y.V2 (and the related virus from Brazil) may be less sensitive to NAbs, but not to an extent that will cause widespread vaccine failure.”
Moreover, “We’ve learned that if you take blood serum from somebody who was previously infected with the old version of the virus, and you try to use that serum to stop the virus-containing this new mutation, you need a higher concentration of the blood serum to neutralize the virus,” David Kennedy, assistant professor of Biology, wrote for The Conversation.
So, there’s more to immunity than antibodies alone. Indeed, mRNA vaccines also induce T-cell immunity that works in tandem with other parts of the immune system. So, decreased antibody efficacy alone doesn’t prove that a particular vaccine is less effective at preventing the disease.
In sum, while there’s evidence of SARS-CoV-2 evolving vaccine resistance, the situation isn’t doomed. If anything, this is “all the more reason why we should be vaccinating as many people as you possibly can,” said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases and health advisor of the White House. More immunized persons would mean fewer hosts for the SARS-CoV-2 to evolve in.
Initially, mathematical modeling data showed that the U.K. mutant is 70% more transmissible. More recent data downgraded the U.K. mutant’s transmissibility to 30–50%, but this might have partly due to lockdown.
Besides, the winter season might have contributed to such founder effect or superspreader events since coronaviruses survive better in cold settings.
But modelings don’t prove that the mutant itself spreads faster. Experts questioned whether the rise in U.K. mutant is due to superspreader events that led to the ‘founder effect,’ where a mutation in a small group ends up spreading to larger groups, and the effect compounds. The founder effect occurs by chance, and the mutation doesn't provide any survival advantage. Besides, the winter season might have contributed to such founder effect or superspreader events since coronaviruses survive better in cold settings.
Thus far, we still don’t know if the U.K. or South African mutants are more contagious among humans. Animal experiments would be needed to confirm this, such as that previously done with the D614G mutant, where it was more contagious among mice and hamsters.
However, there’s theoretical evidence that the SARS-CoV-2 mutants might be more contagious. The N501Y mutation found in the U.K. and South African mutants opens up the virus’s receptor-binding domain (RBD), priming it in such a way that it binds and infects human cells easier. At the same time, the opened RBD exposes the virus to antibody neutralization. So, both effects negate each other, which may explain why increased cell infectivity doesn’t mean increased disease severity.
The evidence is vague but leans towards increased fatality from the U.K. mutant. Vague results may also be a good thing. If the U.K. mutant is literally deadlier, then all reports would show an increased CFR.
But there’s now news that the U.K. mutant might be 30% deadlier than the previous variant. This is based on a report review by the New and Emerging Respiratory Virus Threats Advisory Group (NERVTAG) in the U.K. This review compiled unpublished data from various sources — including the London School of Hygiene and Tropical Medicine (LCHTM) and Imperial College London — which compared the case fatality rate (CFR) of old vs. new SARS-CoV-2 variants occurring within a time period. Overall:
- 6 reports (unpublished data) found an increased CFR of about 30% when infected with the new U.K. mutant. This would mean that 13 out of 1,000 people could die from the mutant, compared to 10 out of 1,000 people with the old variant.
- 4 reports (unpublished data) found no significant differences in CFR between the old and new U.K. variants.
Evidently, preliminary data have been inconsistent in determining if the U.K. mutant is deadlier. NERVTAG also admits that the sample sizes were small — only 8% of deaths were from the U.K. mutant, which might not reflect the general population. Hospitalization data are not collected on most of the reports, so crucial data were left out. Patrick Vallance, the UK’s chief scientific advisor, also admitted that the evidence is “uncertain.”
So, the evidence is vague but leans towards increased fatality from the U.K. mutant. Vague or inconsistent results may also be a good thing. If the U.K. mutant is literally deadlier, then all reports would show an increased CFR. But only 6 out of 10 did; that’s close to 50–50 split.
Others raised the possibility that the U.K. variant, by being more contagious, might be more likely to reach the vulnerable populations — such as senior citizens — at risk for severe Covid-19. Or that the spike in cases overwhelms the healthcare system, putting more people in insufficient care due to scarce resources.
In fact, increased transmissibility is much more dangerous than increased fatality rate. Dr. Christian Yates, a senior lecturer in mathematical biology, explained this concept nicely in The Conversation. Based on the graph below, the death toll of more contagious virus compounds with time, which would eventually exceed the death toll of a deadlier virus.
The emergence of many mutants shows us why we shouldn't let SARS-CoV-2 runs its course. Vaccine resistance has started evolving in the South African mutant, leading to lower antibody efficacy, but it still gets the job done in neutralizing the viruses. Plus, vaccine-induced immunity isn't solely antibody protection but involves other aspects of the immune system like T-cells. Although evidence is still inconclusive, the South African and U.K. mutants might be more contagious and deadlier. As a more contagious virus is more dangerous than a more lethal virus, stopping transmission is the priority. Everyone knows what that entails; that means masks, physical distancing, and vaccination before it’s too late. When vaccine-resistance blooms, then it’s too late and newer vaccines might have to be developed again.
30th Jan update: For more info on how other vaccines fare against the mutants in clinical trials, kindly see here. Briefly, the Novavax protein-based vaccine is 95.6% effective against the old SARS-CoV-2, 85.6% against the U.K. mutant, and 49.4% to 60% against the South African mutant. The Johnson & Johnson adenoviral vaccine is 72% effective in the U.S., but 57% effective against the South African variant. The Moderna and Pfizer-BioNTech mRNA vaccines are about 95% effective against the old SARS-CoV-2, but there’s no clinical data yet about its effectiveness against the mutants. However, it’s clear that vaccine resistance is coming.