Why the Mutated Coronavirus Variants Are So Worrisome

During replication, a virus often undergoes genetic mutations that may create what are called variants. Some mutations weaken the virus; others may yield some advantage that enables the variant to proliferate. Variants with distinctly different physical characteristics may be co-termed a strain. A variant that deviates significantly from its viral ancestors may be identified as a new lineage, or branch on the evolutionary tree. In general discourse, however, the terms are often used interchangeably.

2. How widespread are these variants?

The variant that emerged in England in September, B.1.1.7, contributed to a surge in cases that sent the U.K. back into lockdown in January. Other countries followed, particularly in Europe. In the U.S., health officials have warned the strain could become dominant as soon as March; President Joe Biden toughened rules in his first days in office to try to contain it. In southern Africa, hospitals faced pressure from a resurgence driven by another variant, 501Y.V2 (also known as B.1.351). Brazilian researchers, meanwhile, have warned that a so-called P.1 variant spotted in Manaus, Amazonas state, in December may have driven a surge in cases that strained the health system and led to oxygen shortages. Researchers in Los Angeles reported a novel strain, denoted as CAL.20C or B.1.427, linked to a surge of coronavirus cases in Southern California. Preliminary research indicates it’s slightly more transmissible and may moderately resist antibodies generated from a previous SARS-CoV-2 infection. Insufficient surveillance in most countries, including the U.S., has obscured recognition of variants circulating in many places. Improved monitoring has led scientists to discover more strains in New York and elsewhere, though less is known about them.

3. What are the concerns with these variants?

Broadly, they pose different concerns of varying degrees. These relate to their:

• Transmissibility, or propensity to spread

• The severity of illness they cause

• Neutralization capacity, or the likelihood they will infect people who have recovered from a previous bout of Covid-19, and

• Potential impact on vaccination through their ability to evade the protection that immunizations are designed to generate

The World Health Organization’s March 9 assessment is summarized below:

4. How quickly have the strains spread?

Rapidly, aided by year-end holidays traditionally associated with increased family and social mixing. As of March 9, imported cases or community transmission of the B.1.1.7 variant from the U.K. had been reported in 111 countries, according to the WHO. In the U.S., scientists have estimated that infections caused by B.1.1.7 are doubling every 10 days. As of March 9, scientists have found the 501Y.V2 variant that first appeared in South Africa in early August in 58 countries, while 32 countries are reported to have detected the P.1 variant first seen in Brazil, according to the WHO.

5. How are the variants increasing transmission?

They appear to have some advantage over other versions that has enabled them to quickly predominate, although factors such as people congregating indoors more in colder weather may also contribute to spread. The U.K. strain has acquired 17 mutations compared with its most recent ancestor — a faster rate of change than scientists typically observe. A U.K. advisory group said in December that the B.1.1.7 lineage may result in an increase in the basic reproduction number, or R0 (the average number of new infections estimated to stem from a single case) in the range of 0.39 to 0.93 — a “substantial increase.”

6. So why are cases falling?

Worldwide, by late February the number of new Covid-19 cases reported weekly has fallen steeply from a peak in early January. That’s coincided with more stringent public health measures — from physical-distancing and mask-wearing requirements to lockdowns — as well as rising rates of infection- and vaccine-induced immunity. Some scientists have speculated that SARS-CoV-2 may have a seasonal pattern, causing comparatively more infections in late autumn and early winter-type weather. It’s possible cases may climb again as more-transmissible variants seed fresh epidemics.

7. How many mutations are there?

Many thousands of mutations and distinct lineages have arisen in the SARS-CoV-2 genome since the virus emerged in late 2019. A variant with a so-called D614G mutation emerged in early 2020. By June, it had replaced the initial strain identified in China to become the dominant form of the virus circulating globally. Months later, a novel variant linked to farmed mink was identified in a dozen patients in North Jutland, Denmark, but doesn’t appear to have spread widely. As SARS-CoV-2 continues to circulate, more mutations will arise, potentially leading to more variants.

8. Are some mutations more important?

Yes. Scientists pay most attention to mutations in the gene that encodes the SARS-CoV-2 spike protein, which plays a key role in viral entry into cells. Targeted by vaccines, this protein influences immunity and vaccine efficacy. The B.1.1.7, 501Y.V2, and P.1 variants all carry multiple mutations affecting the spike protein. That raises questions about whether people who have developed antibodies to the “regular” strain — either from a vaccine or from having recovered from Covid-19 — will be able to fight off the new variants.

9. What do we know so far?

In January Public Health England found those previously infected with the “regular” coronavirus are likely to mount an effective antibody response against the B.1.1.7 variant. But the same month the first known instance of a recovered Covid-19 patient being reinfected with the P.1 variant was reported in Brazil. That strain has several key mutations in common with the 501Y.V2 strain from South Africa, that was associated with some 4,000 reinfections in people who had already experienced Covid-19 in an earlier epidemic. In a Jan. 28 editorial in the Journal of the American Medical Association, virologist John P. Moore and vaccinologist Paul Offit described the 501Y.V2 variant as “more troubling” because of its potential for reducing vaccine efficacy, due to its particular spike-protein mutations.

10. How effective will vaccines be?

Data are emerging, and no clinical studies have directly compared different vaccine types and their ability to protect against the new strains. Overall, nine vaccines have proved effective in clinical trials at preventing severe disease and death from Covid-19. The studies suggest, however, that some may not be as good at stopping less severe illness in countries where particular variants predominate. Notably:

• Shots from both Novavax Inc. and Johnson & Johnson showed lower efficacy in South Africa compared with other countries.

• South Africa announced plans in early February to halt its rollout of the AstraZeneca vaccine. An interim analysis of clinical trial results there found two doses of the vaccine didn’t protect recipients against mild-to-moderate Covid-19 from the 501Y.V2 variant, though researchers speculated that the regimen might still protect against severe illness. A WHO advisory panel cautioned that the 21-to-35-day interval between the first and second doses isn’t optimal for inducing immunity and larger studies are needed.

• A study published Feb. 24 of almost 1.2 million people in Israel, which has inoculated a higher percentage of its population than any other country, estimated that the Pfizer Inc.-BioNTech SE vaccine was 92% effective in preventing all infections. By the end of the surveyed time period, as many as four-fifths of the infections in Israel were caused by the B.1.1.7 variant first identified in the U.K.

• Scientists at the Fred Hutchinson Cancer Research Center in Seattle found a single jab of either the Moderna or Pfizer-BioNTech shot bolstered the immune response in 10 patients who had recovered from a SARS-CoV-2 infection early in the pandemic. The concentration of neutralizing antibodies in the recipients’ blood increased about a thousand-fold, and they appeared potent against the 501Y.V2 variant first identified in South Africa.

11. What are drugmakers doing?

Sarah Gilbert, a professor of vaccinology at the University of Oxford who conducted the initial research on the AstraZeneca vaccine, said that “efforts are underway to develop a new generation of vaccines that will allow protection to be redirected to emerging variants as booster jabs, if it turns out that it is necessary to do so.” The new shot could be ready for the fall, she told the BBC. Pfizer and its German partner BioNTech, as well as Moderna, have said their own results indicate their vaccines should still work against the strain detected in South Africa, despite the reduced potency. Nevertheless, Moderna said March 10 that it began testing modified Covid-19 vaccines, designed to address the potential need for booster vaccine candidates, in clinical trial participants. Pfizer and Novovax also have said they’re working on either a booster or combination shot. Such alterations aren’t unheard of — it happens annually with seasonal flu, which evolves quickly. Unlike flu, coronaviruses have a genetic self-correcting mechanism that minimizes mutations.

12. Could different vaccines be used in combination?

Potentially, yes. The Coalition for Epidemic Preparedness Innovations, or CEPI, announced in January as much as $140 million in funding for additional clinical research to optimize and extend the use of existing vaccines. This could include “mix-and-match” studies of different shots in combinations that may improve the quality and strength of the immune response. Such studies could be useful in optimizing the use of available inoculations, including the AstraZeneca shot, according to the WHO.

13. Are there any other implications?

Yes, treatments and diagnostics could be affected. Researchers in South Africa found a theoretical risk that some antibodies being developed for therapeutic use could be ineffective against the 501Y.V2 variant prevalent there. But studies at Columbia University support tests by Regeneron Pharmaceuticals Inc. showing that its antibody cocktail, which was granted emergency-use authorization in the U.S. and administered to Donald Trump, is effective at neutralizing 501Y.V2 and the variant first identified in the U.K. Drugmakers are using combinations of antibodies that target separate features of SARS-CoV-2 to decrease the potential for so-called virus-escape mutants that could emerge in response to selective pressure from a single-antibody treatment. The U.S. Centers for Disease Control and Prevention has said new strains might undermine the performance of some PCR-based diagnostic tests. The impact, though, isn’t likely to be significant, according to the WHO.

(Updates information about California variant in section 2; tabulated information in section 3; numbers of countries reporting variants in section 4; Moderna clinical trial information in section 11.)

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