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 and elsewhere. Drugmakers say their vaccines should still work, although some are looking at new versions. Some researchers warn the shots may need to be updated periodically to maintain their efficacy.

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. The European Centre for Disease Prevention and Control on Jan. 21 raised the risk of spread of the new variants in the European Union to “very high.” 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. 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. Much less is known about this variant, which has been found in the U.S., Japan, and South Korea among travelers from Brazil. 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. Johnson said the number of Covid patients hospitalized as of Jan. 22 — 38,562 — was 78% higher than during the first peak last April.

3. How quickly have the strains spread?
Rapidly. They have become the dominant strains in multiple countries, aided by year-end holidays that are traditionally associated with increased family and social mixing. By early January, cases caused by the B.1.1.7 variant had been identified in some 50 countries or territories, including the U.S., Australia, Canada, Germany, Italy, Japan, Lebanon, the Netherlands, Singapore and South Korea. Similarly, the 501Y.V2 variant that was first detected in Nelson Mandela Bay, South Africa, in early October has led to a steep rise in cases across nine southern African countries as well as the Seychelles and Mauritius. By mid-January, 501Y.V2 had been identified in 10 countries in Europe, with clusters of cases reported in the U.K. and Israel and another under investigation in France.

4. How much are the variants increasing transmission?
The new variants 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. Scientists in South Africa have found the new strain there is about 50% more transmissible than earlier versions. The variant in the U.K. has been found to be 56% to 70% more transmissible. It has acquired 17 mutations compared to its most recent ancestor — a faster rate of change than scientists typically observe. A U.K. advisory group noted 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.” Public Health England reported in January that patients infected with the variant were more likely to infect their contacts than if they had a “regular” strain.

5. 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.

6. 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.

7. 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. In a Jan. 28 editorial in the Journal of the American Medical Association, virologist John P. Moore and vaccinologist Paul Offit described the variant that emerged in South Africa as more “more troubling” because of the number and position of its spike-protein mutations and the potential effects on vaccine efficacy. A late-stage study conducted in the U.K. and South Africa on an experimental vaccine from Novavax Inc. appeared to support those concerns. Interim results found the shot was 89.3% effective in preventing symptomatic Covid-19 among trial participants in the U.K. and remained effective against the more transmissible B.1.1.7 strain. But it was only 60% effective in the vast majority of people enrolled in South Africa who were HIV negative. It was 49.4% effective overall when HIV positive patients were also counted.

8. So how effective will vaccines be?
Research is ongoing, but results so far are inconclusive, in part because laboratory studies aren’t able to reproduce the body’s full range of immune responses to a virus. In addition to creating a strong antibody response, the messenger RNA vaccines made by Moderna Inc. and Pfizer Inc.-BioNTech activate a person’s own T cells (white blood cells that form another part of the body’s defense system). That may help generate broader immune protection that will mitigate any reduction in antibody sensitivity, Moore and Offit said. Conversely, vaccines that appear to induce lower levels of so-called neutralizing antibodies, such as those developed in China and India, maybe less effective, they said. In other research:
South Africa’s National Institute for Communicable Diseases studied blood samples from 44 patients previously infected with the coronavirus to check if their antibodies would fight off the new variant there. The cohort was small but, worryingly, half of the samples tested indicated all neutralizing activity was lost, suggesting that those people may no longer be protected. In the other patients, antibody levels were reduced, but those individuals had started from a higher level, having recovered from severe Covid-19. The scientists cautioned that the lab studies are only indicative. They said they have no evidence that this is actually occurring in the community, or whether vaccine-generated antibodies will be less effective against the new strain.
Experiments at Rockefeller University in New York indicate that variants, including B.1.1.7, 501Y.V2, and P.1, may negate the potency of the Moderna Inc. and Pfizer-BioNTech vaccines, according to a study released on Jan. 19 ahead of publication and peer-review. Researchers are working to understand this better.

9. What are drugmakers doing?
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. The University of Oxford, which partnered on the AstraZeneca Plc vaccine, said it’s evaluating what it would take for rapid deployment of “adjusted” versions to combat emerging variants if needed. Novavax said it started working on new versions of its vaccine targeting the emerging strains in early 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.

10. Are there any other implications?
Yes, treatments and diagnostics could be affected. Researchers in South Africa have found that some antibody therapies, including the Regeneron Pharmaceuticals Inc. product, granted emergency use authorization in the U.S. and administered to Donald Trump, may be ineffective against the 501Y.V2 variant. 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