By now, most of you have heard the stories about the new variants/strains of the COVID-19 virus, especially those found in the U.K., South Africa and Brazil, and how that may change the dynamics of the pandemic and the efficacy of the vaccines. Let’s take stock of what we know, what we do not know and what public health experts are saying about it.
Summary
There are 3 Coronavirus variants of concern at this time —
A new variant of B.1.1.7, which has another mutation that reduces current vaccine effectiveness, is brewing in the U.K.
These variants have scientists and the CDC concerned. There are predictions that these variants, or mutations thereof, may become the dominant ones in the world soon.
These three variants have been detected in the U.S., so they are already here. But more variants are brewing as the pandemic rages around the world.
The Novax vaccine trial showed slightly lower efficacy against the B.1.1.7 virus but prevented severe illness and death.
The Novavax and J&J vaccines have shown lower efficacy in preventing disease against the B.1.351 variant, although both vaccines prevented severe illness and death.
All vaccine companies are developing modified vaccines based on the genetic code of these new emerging variants.
Mutations and Variants
We have heard repeatedly that viruses mutate regularly, but most mutations do not affect its infectiousness or lethality. But scientists have always cautioned that some mutations may make the virus more infectious, more lethal or better at evading antibodies generated by past infections or current vaccines. And the more virus is out there, the greater the probability of mutations that may harbor one or more these properties and which may spread across the population.
In fact, the original virus that landed on our shores was pretty much replaced by the more infectious variant known as D614G in summer last year. There are thousands of other variants that are tracked by virus experts.
The Variants
Here is a quick summary of the 3 variants -
501Y.V3
N501Y, E69/70 deletion, P681H, Y144 deletion, orf1ab deletion
>29% suspected
65% according to this report
The N501Y mutation affects the receptor binding domain (RBD) of the spike protein, which the virus uses to clasp onto the ACE2 receptors on the surface of human cells. The mutation potentially allows the virus to bind more tightly to ACE2 receptors, facilitating entry into the cell. That makes the virus spread faster inside the body thereby increasing the chances of developing symptoms and severe disease. All 3 variants carry this mutation.
The E484K mutation is associated with the variants from S. Africa and from Brazil. There is some evidence that it makes the virus more resistant to antibodies.
The reduced vaccine efficacy for B.1.351 is supported by results from Novavax and J&J and also by in-vitro tests.
B.1.351 and P.1 emerged independently in areas with high levels of previous infections, which supports the hypothesis that the virus can evolve to evade antibodies in patients that have prolonged illness and whose bodies are not able to kill the virus entirely.
B.1.1.7 has spread quite rapidly in the U.K. -
So this graph from the latest NERVTAG shows that the new B117 variant is now dominant in all English regions taking around 7-8 weeks to go from less than 10% of cases to 80%+. Many countries in Europe currently at about 5-10%... pic.twitter.com/lsRo5zbsON— Christina Pagel (@chrischirp) February 2, 2021
So this graph from the latest NERVTAG shows that the new B117 variant is now dominant in all English regions taking around 7-8 weeks to go from less than 10% of cases to 80%+. Many countries in Europe currently at about 5-10%... pic.twitter.com/lsRo5zbsON
So have the others in S. Africa and Brazil -
Startling how fast variant #SARSCoV2 take over, dominating #COVID19 epidemics.- In UK/December 43% of tested viruses were B.1.1.7 mutant: Now it's 77%.- In Dec/So Africa 89% of samples = B.1.351: Now it's 100%.- Brazil/Dec 38% were B.1.1.28 : Now 62%.https://t.co/bDRZ0IDXEK— Laurie Garrett (@Laurie_Garrett) February 2, 2021
Startling how fast variant #SARSCoV2 take over, dominating #COVID19 epidemics.- In UK/December 43% of tested viruses were B.1.1.7 mutant: Now it's 77%.- In Dec/So Africa 89% of samples = B.1.351: Now it's 100%.- Brazil/Dec 38% were B.1.1.28 : Now 62%.https://t.co/bDRZ0IDXEK
All of these variants have been found in the U.S.
5/ The CDC has predicted that the B.1.1.7 variant from the UK will likely become the dominant strain the U.S. by March. https://t.co/SMh1kBo0GF— Céline Gounder, MD, ScM, FIDSA (@celinegounder) January 28, 2021
5/ The CDC has predicted that the B.1.1.7 variant from the UK will likely become the dominant strain the U.S. by March. https://t.co/SMh1kBo0GF
Updated mortality rate for B.1.1.7 -
Risk ratio of B117 updated to 1.65 (95% confidence interval is 1.21-2.25) in latest technical report (thats 65% higher mortality).https://t.co/eytKTdGsno— Aris Katzourakis 💙 (@ArisKatzourakis) February 2, 2021
Risk ratio of B117 updated to 1.65 (95% confidence interval is 1.21-2.25) in latest technical report (thats 65% higher mortality).https://t.co/eytKTdGsno
Yet another Variant
Now there is evidence that the B.1.1.7 strain the U.K. has evolved to include the E484K mutation. The new variant has been detected in patients and is raising alarms in the scientific community.
And now for the bad news. *sigh*It looks like #B117, the more transmissible variant first detected in England, has now picked up the E484K mutation as well. That is the one linked to evading SOME immunity in SAfrica and Brazil.h/t @_b_meyerhttps://t.co/2iQLr8uJx7— Kai Kupferschmidt (@kakape) February 1, 2021
And now for the bad news. *sigh*It looks like #B117, the more transmissible variant first detected in England, has now picked up the E484K mutation as well. That is the one linked to evading SOME immunity in SAfrica and Brazil.h/t @_b_meyerhttps://t.co/2iQLr8uJx7
It is not known whether the E484K mutation will help B.1.1.7 evade antibodies in humans. The impact of a single new mutation on a virus depends on the other mutations that the variant already carries.
But, tests with lab-created pseudo-viruses with B.1.1.7 mutations + E484K show that a substantially larger amount of serum antibody is needed to prevent infection of cells. Pre-print paper at www.medrxiv.org/...
We generated 'pseudo' viruses bearing the Spike protein of SARS-CoV-2 that had all 8 B.1.1.7 mutations + E484K. We mixed virus with sera from vaccinated individuals (Pfizer) Overall, E484K substantially increases the amount of serum antibody needed to prevent infection of cells. pic.twitter.com/K2hcjYzDnv— Gupta Lab, Cambridge (@GuptaR_lab) February 2, 2021
We generated 'pseudo' viruses bearing the Spike protein of SARS-CoV-2 that had all 8 B.1.1.7 mutations + E484K. We mixed virus with sera from vaccinated individuals (Pfizer) Overall, E484K substantially increases the amount of serum antibody needed to prevent infection of cells. pic.twitter.com/K2hcjYzDnv
Vaccine results against these variants
We now have vaccine data against two of the emerging virus variants, thanks to the late clinical trials by Novavax and J&J.
Overall
Original Strain
D614G
UK
Strain B.1.1.7
S. Africa
Strain B.1.351
62%
U.K. and L. America
AstraZeneca
(½ + full dose)
90%
72%
U.S. and L. America
96%
(in U.K)
49.4%
60% for HIV-neg patients
Notes:
See diary “A Comparison of the leading COVID-19 Vaccines” for more details about the vaccines.
Vaccine Variants
The technology used in these vaccines makes it quite easy to modify them for new variants. Once the genetic sequence of the new variant is known, the mRNA/DNA/protein can easily be modified accordingly.
The new vaccines might be delivered as a 3rd dose or a mix of vaccine variants in the first or second dose.
It is not clear what level of clinical trials will be needed for these variant vaccines and how long it will take. Expectations are for approval in fall.
Overall, the Novavax and J&J results bode well for the future, since we need billions of doses to get the world population vaccinated soon. The longer the virus lingers and thrives in the population, the higher the chances of it mutating, becoming more infectious and becoming resistant to existing vaccines. And others have pointed out, it does no good if one country is fully vaccinated but others aren’t; the virus will thrive and mutate in countries with low levels of vaccination and it will then land on other shores.
Speed of vaccination is of the essence right now, so that the virus spread can be brought under control soon.
Speed of vaccination is also driving the debate whether we should use up all vaccine stock right away and administer the first dose to the maximum number of individuals, and perhaps delay the 2nd dose by a few weeks, rather than reserve and store away the second doses and administer them on time. The other side of the coin is that the delayed 2nd dose might give the virus a chance to evolve against the vaccine inside patients where certain variants selectively survive against a diminished immune response.
There is genuine concern that the B.1.1.7 and B.1.351 variants, and possibly the variant from Brazil P.1, will become dominant worldwide in the next few months.
There is also concern that as vaccination levels rise, it will put selection pressure on the virus to evolve into B.1.351 or P.1 -like variants, that can evade antibodies generated by current vaccines. It might mean periodic updates to vaccines and annual shots, just like the flu.
And let’s not even talk about what would have happened with virus mutations if trump had won the election and gone ahead with the let-everyone-get-infected herd-immunity racket.
Here is an insightful thread about the future spread of the 3 variants from a preeminent immunologist at the Scripps Institute.
However, I'm concerned this will change as we (necessarily) build more immunity in the population (via critically important vaccination) - B.1.351, P.1, and other lineages picking up the same / similar key mutations, will then have a fitness advantage and rise in frequency.— Kristian G. Andersen (@K_G_Andersen) January 31, 2021
However, I'm concerned this will change as we (necessarily) build more immunity in the population (via critically important vaccination) - B.1.351, P.1, and other lineages picking up the same / similar key mutations, will then have a fitness advantage and rise in frequency.
Here is a timely article — on what needs to be done to combat these emerging variants.
Steps to confront rise of #SARSCoV2 variants:•Isolate virus from hospitalized vaccinees•Active sequencing, surveillance •Test vaccinees’ sera vs variants•Adjust vaccines to match emerging variants•Continue masks, physical distancing, handwashing https://t.co/TAsKFsCyM9— Marilyn Heine (@MarilynHeineMD) January 29, 2021
Steps to confront rise of #SARSCoV2 variants:•Isolate virus from hospitalized vaccinees•Active sequencing, surveillance •Test vaccinees’ sera vs variants•Adjust vaccines to match emerging variants•Continue masks, physical distancing, handwashing https://t.co/TAsKFsCyM9
Epilogue
Variants B.1.1.7, B.1.351 and the new B.1.1.7 variant with the E484K mutation are all cause for serious concern.
Speed of vaccination is of the essence right now, so that the virus spread can be brought under control soon. More virus means more chances of dangerous mutations. Hence, we should all get whatever vaccine becomes available ASAP and recommend the same to others.
All this also means that we should not let our guard down after getting the vaccine. Social distancing and masking will remain useful tools even after vaccination, until most of the population is vaccinated and infection rates reduce to a trickle.
We might need new vaccine variants soon, we might end up with annual vaccine shots similar to flu vaccines. But in any case, the less virus there is, the less the chances of getting infected and of creating and spreading harmful mutations. Let’s all be prepared and do our part to save ourselves and to save others. It’s heartening to know that we now have a super-competent and serious team in the new administration which is providing real leadership in the fight against this pandemic.
Get vaccinated. Save lives. pic.twitter.com/5ZNXerlmIJ— Vice President Kamala Harris (@VP) January 29, 2021
Get vaccinated. Save lives. pic.twitter.com/5ZNXerlmIJ
Further Reading
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