Why the Mutated Coronavirus Variants Are So Worrisome: QuickTake

LAGOS (Capital Markets in Africa) — Viruses mutate all the time, including the novel coronavirus that’s caused the global Covid-19 pandemic. Most of the changes have no apparent effect. But recent variants that have emerged in the U.K., South Africa, and Brazil are causing particular concern. Studies suggest they are more contagious, and some evidence points to the U.K. strain being more deadly. An increase in infections has led to a surge in hospitalizations and deaths in England, Portugal, and elsewhere. Vaccine developers are working on new versions after early data from South Africa indicated AstraZeneca Plc’s inoculation was less effective against the variant circulating there.

1. How widespread is this?
The variant that emerged in southeast England in September, dubbed the B.1.1.7 lineage, contributed to a surge in cases that sent the U.K. back into lockdown in January. Other countries have followed, particularly in Europe, and are ratcheting up precautions like wearing masks. 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 are facing pressure from a resurgence driven by another variant, 501Y.V2 (also known as B.1.351). Brazilian researchers are warning 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 at Cedars-Sinai Medical Center in Los Angeles say a novel strain has emerged in California, though less is known about its importance and some scientists have questioned its existence.
Viruses mutate all the time. How worrisome are new coronavirus variants? Bloomberg News’s Jason Gale explains.

2. How serious is it?
U.K. Prime Minister Boris Johnson said on Jan. 22 that new evidence had led the government to revise its original view that the B.1.1.7 variant wasn’t more dangerous. The government said that on average, for 1,000 men in their 60s, 13 to 14 would die if they contracted the new variant, compared to 10 for the original strain of SARS-CoV-2. However, quality of care could also play a role: Another U.K. study found mortality rates were higher for Covid patients admitted to intensive care during high-occupancy periods, and decreased for admissions when the unit was less full. (The number of Covid patients hospitalized in the U.K. as of mid-January was far higher than during the first peak last April.) Public Health England noted in early February emerging evidence of an additional mutation in the B.1.1.7 variant that may weaken any immune protection gained from current vaccines or naturally from a previous infection with an earlier strain.

3. Do the new variants cause different symptoms?
Some subtle differences have been noted in symptom patterns among U.K. patients infected with the B.1.1.7 variant compared with other strains. The former are more likely to have a cough, sore throat, fatigue or myalgia, according to a report in the BMJ. Data from the U.K. Office for National Statistics indicate people with the new variant there are less likely to experience losing the sense of smell or taste. The findings prompted some doctors to call for the official Covid-19 symptom list to be reviewed and potentially expanded for the first time since May.

4. How quickly have the strains spread?
Rapidly, aided by year-end holidays that are traditionally associated with increased family and social mixing. As of Feb. 2, imported cases or community transmission of the B.1.1.7 variant from the U.K. had been reported in 80 countries, according to the World Health Organization. Scientists estimate that B.1.1.7 is doubling in the U.S. every 10 days, with at least a 35-45% higher transmission rate than previous strains. Similarly, scientists have found the 501Y.V2 variant that was first detected in Nelson Mandela Bay, South Africa, in early October is about 50% more transmissible than earlier versions. It has led to a steep rise in cases across southern Africa as well as the Seychelles and Mauritius. As of Feb. 2, 501Y.V2 had been identified in 41 countries, while 10 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 have enabled them to quickly predominate, although factors such as people congregating indoors more in colder weather may also contribute to spreading. The U.K. strain has acquired 17 mutations compared to 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. 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 mutations continue to arise, they will lead to more new variants.

7. 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.

8. 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. In a Jan. 28 editorial in the Journal of the American Medical Association, virologist John P. Moore and vaccinologist Paul Offitdescribed the 501Y.V2 variant as “more troubling” because of its potential for reducing vaccine efficacy, due to its particular spike-protein mutations.

9. So how effective will vaccines be?
Moore and Offit’s concerns appear well-founded, with clinical trials of candidate shots from both Novavax Inc. and Johnson & Johnson showing lower efficacy in South Africa compared to other countries. Although vaccines studied in late-stage clinical trials appear effective at preventing severe disease in the majority of participants, there is emerging evidence that some may not be as good at stopping less-severe illness. South Africa announced plans in early February to halt its rollout of the AstraZeneca vaccine after preliminary data suggested the shot “provides minimal protection” against mild disease caused by the variant circulating there. However, a WHO advisory panel reviewing the AstraZeneca vaccine said that study had limitations, including its size and focus on low-risk participants, and it used interval doses that weren’t optimal for inducing immunity. There is also no data to determine the extent to which immunization will prevent asymptomatic infection and transmission of SARS-CoV-2, including the new strains.

10. Will some vaccines are more protective?
Most likely. Although there have been no clinical studies directly comparing different types and their ability to protect against the new strains, lab studies have indicated that the so-called mRNA vaccines from Moderna Inc. and Pfizer Inc.-BioNTech SE may be more effective than other types. 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 South African variant.

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 it plans to develop and test a third-shot booster against that variant, and Pfizer’s chief executive officer also said his company is starting the development of a booster against the new mutations. Novavax said it started working on new versions of its vaccine targeting the emerging strains in January and expects to select ideal candidates for 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 up to $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 used 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 World Health Organization.

Source: Bloomberg Business News