From Alpha to Delta, Why Virus Mutations Cause Alarm

(Bloomberg) -- Viruses mutate all the time, including the SARS-CoV-2 coronavirus that’s caused the Covid-19 pandemic. Although most genetic changes are innocuous, some can make the mutant more adept at infecting cells or evading antibodies, for example. Such “fitter” variants can outcompete other strains, so that they become the predominant source of infections. A succession of more-transmissible coronavirus variants has emerged over the past year, each harboring a constellation of mutations. The most worrisome so far is the so-called delta variant. It has spread to almost 100 countries since it was first reported in India in October, leading to surges in cases and hospitalizations, especially in places where less than half the adult population has been fully immunized.

1. What’s a variant?

During replication, a virus often undergoes genetic changes that may create what are called variants. Some mutations weaken the virus; others may yield an advantage that enables it to proliferate. If changes produce a version with distinctly different physical characteristics, the variant 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. What are the most worrisome ones?

The World Health Organization uses “variants of concern” to signify strains that pose additional risks to public health. It uses “emerging variants of interest” for those that warrant close monitoring because of a increased potential risk. These have been assigned letters from the Greek alphabet for identification. As of June 29, the WHO has identified four variants of concern and seven variants of interest. They are:

Alpha

This variant emerged in England in September 2020 and drove a winter surge in cases that sent the U.K. back into lockdown in January. Other countries, particularly in Europe, followed the U.K. in reimposing movement restrictions. Alpha became the dominant strain in the U.S. in early April and has been reported in at least 172 countries, according to the WHO.

Beta

This one, which appeared in South Africa in August 2020, led to a resurgence in Covid cases that overwhelmed southern Africa. It’s been reported in at least 120 countries.

Gamma

This variant, first spotted in the Amazon city of Manaus in December 2020, has contributed to a surge in cases that strained Brazil’s health system and led to oxygen shortages. It’s been reported in at least 72 countries.

Delta

This fast-spreading variant stoked a dramatic wave of Covid cases in India that overwhelmed hospitals and crematoriums and has since been found in at least 96 countries. It’s estimated to be 55% more transmissible than alpha, researchers from the WHO, London School of Hygiene and Tropical Medicine, and Imperial College London said in a study in mid-June. That advantage is likely to see it become the dominant variant over the coming months, they said. Doctors in India have linked delta to a broader array of Covid symptoms, including hearing impairment, and Public Health England said in June that data from both England and Scotland suggest an increased risk of hospitalization compared to alpha. Other evidence showed delta had some propensity to evade antibody-based treatments and that it potentially increased the risk of reinfection in people who have recovered from Covid caused by another strain.

3. How do variants affect the vaccines?

Scientists pay the most attention to mutations in the gene that encodes the virus’s spike protein, which plays a key role in its entry into cells and is targeted by vaccines. The four variants of concern all carry multiple mutations affecting the spike protein. That raises questions about whether people who have developed antibodies to the “regular” or “wild type” strain -- either from a vaccine or from having recovered from Covid -- will be able to fight off the new variants. University of Florida researchers found that for the Covid vaccines being rolled out on a global scale, the alpha strain led to “somewhat reduced” efficacy compared with the wild strain, while the beta and gamma variants led to considerably lower efficacy, they said in a paper released in May ahead of peer-review, in which research is scrutinized by experts in the same field before publication. As for delta, data from Public Health England indicate that vaccines are less effective at preventing symptomatic disease compared with alpha, especially after only one dose.

Other research indicates that two doses of vaccine may still protect against severe Covid.

4. Are some vaccines better?

No clinical trials have directly compared the ability of different vaccines to protect against the original strain, let alone variants. Still, emerging data suggest there will be differences in efficacy. Research by Public Health England released before peer review and based on patient records found two doses of the AstraZeneca Plc vaccine were less effective at preventing Covid-19 caused by delta compared with a double dose of the inoculation made by Pfizer Inc. and its partner BioNTech SE.

Public Health England also found that a single dose of the Pfizer-BioNTech shot did a better job at protecting against hospitalization with the delta variant than the AstraZeneca vaccine. Effectiveness was similar after two doses, though.

The finding corresponded with data from the Francis Crick Institute in London published in The Lancet on June 28 that underscored the importance of a second vaccine dose for increased protection against delta and suggest that further booster immunizations might be needed, especially for more susceptible groups, such as organ transplant recipients.

5. Could different vaccines be used in combination?

Potentially, yes. That’s already happening to a limited extent, largely because of pauses in the use of AstraZeneca’s vaccine prompted by cases of rare blood clots associated with it. A few small studies, with results not yet peer-reviewed, have suggested that administering a dose of one Covid vaccine followed by a second dose of a different type of Covid shot could be more protective than two doses of the same formulation. Additional studies of vaccine mixing are underway. Such trials could be useful in optimizing the deployment of available inoculations, according to the WHO.

6. Are there other worrisome variants?

New delta variants have been reported in several countries including India, the U.K. and Vietnam. A strain that includes the K417N mutation -- dubbed “delta-plus” in India -- has stoked some concern, since that genetic change is also harbored by the beta strain that’s associated with an increased risk of reinfection. U.K. researchers said in late June that there’s no evidence yet to suggest the additional mutation is more worrisome. The WHO has highlighted the risk that more variants will emerge as the coronavirus continues to spread.

7. What are drugmakers doing?

Sarah Gilbert, a professor of vaccinology at the University of Oxford who conducted the initial research on the AstraZeneca Plc vaccine, told the BBC 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.” Several drug companies have said they’re working on either a booster or combination shot. Such alterations aren’t unheard of -- it happens annually with vaccines against flu, which evolves quickly. Unlike flu, coronaviruses have a genetic self-correcting mechanism that minimizes mutations.

8. Are there any other implications?

Yes. There are implications for treatments, diagnostics and the spread of SARS-CoV-2 in animals.

The Reference Shelf

©2021 Bloomberg L.P.