Just like a Hollywood series that starts sequel after mind-numbing sequel, Omicron it's back.
Just weeks after mutated BA.2 lineages caused a global surge, two other Omicron branches are emerging around the world. BA.4 and BA.5 are the latest members of Omicron’s growing family of coronavirus subtypes. These two viruses were first discovered by South African scientists in April 2020 and were related to the subsequent increase in cases in South Africa. The virus has been detected in dozens of countries around the world.
BA.4 and BA.5 are surging around the world because they are spreading faster than other circulating variants, primarily BA.2, which caused a surge in cases at the beginning of the year. But so far, the latest Omicron variant appears to be causing fewer deaths and hospitalizations than its older cousin, suggesting that growing population immunity is moderating the immediate consequences of the COVID-19 surge.
html On June 23, an article published in Nature magazine explored what the growth of BA.4 and BA.5 mutant strains means for the epidemic. What are
BA.4 and BA.5?
These two variants are more similar to BA.2 than the BA.1 strain that triggered the Omicron epidemic wave in most countries late last year. But BA.4 and BA.5 carry their own unique mutations, including changes to L452R and F486V in the virus's spike protein, which may alter its ability to bind to host cells and thereby bypass certain immune responses.
In May of this year, an article on the medRxiv preprint platform found that BA.4 and BA.5 had the same origin as early Omicron strains. But an unpublished analysis led by evolutionary geneticists Bette Korber and William Fischer at Los Alamos National Laboratory in New Mexico suggests that the mutant strains may be offshoots of BA.2.
Korber and Fischer also found that many genome sequences classified as BA.2 in public databases were actually BA.4 or BA.5. Therefore, researchers may have underestimated the continued growth of mutant strains, as well as the diversity of mutations they carry.
Why are these mutant strains on the rise globally? The transmission advantage of the
variant may come from biological changes that speed up infection, such as allowing the virus to infect more people faster. "But the rise in BA.4 and BA.5 appears to stem from their ability to infect people who are immune to early forms of Omicron and other variants," says Christian Althaus, a computational epidemiologist at the University of Bern.
Since most countries outside Asia have done very little to control SARS-CoV-2, the rise (and inevitable decline) of BA.4 and BA.5 outbreaks will be driven almost entirely by population immunity. Cases increase when protective measures stop and only decrease when enough people are infected.
Based on the rise of BA.5 epidemics in Switzerland (where BA.4 prevalence is lower), Althaus estimates that about 15% of people there will be infected. However, countries may now have different immunity status due to their different histories of COVID-19 epidemic fluctuations and vaccination rates. Therefore, the size of the BA.4 and BA.5 epidemic waves varies from place to place. He said: "In some countries it may be 5%, in other countries it may be 30%. It all depends on their immune status."
What impact will BA.4 and BA.5 have on society?
BA.4 and BA.5 have different impacts on various countries and regions. Waasila Jassat, a public health expert at the National Institute of Communicable Diseases in Johannesburg, said that despite the high number of infections in South Africa, the number of hospitalizations and deaths in South Africa only increased slightly during the BA.4 and BA.5 epidemics.
Jassat and colleagues report in a study soon to be published on medRxiv preprint that the BA.4 and BA.5 epidemics in South Africa resulted in little change in hospitalization rates and even lower mortality compared with earlier Omicron outbreaks. . In terms of hospitalizations and deaths, both Omicron outbreaks were milder in severity than the Delta outbreak.
But outside of South Africa, BA.4 and BA.5 have had more serious consequences.Despite Portugal's high uptake of COVID-19 vaccines and booster shots, the BA.4 and BA.5 outbreaks have brought levels of death and hospitalization similar to the first wave of Omicron.
Althaus said the difference may be due to Portugal's demographic structure. "The more elderly the population is, the more serious the consequences of the disease." Jassat believes that the country's herd immunity is also one of the influencing factors. She said that although only 1/2 of adult South African residents have been vaccinated, and only 5% have received booster shots, due to high infection rates across the country due to the early COVID-19 outbreak, residents have developed a mixed herd immunity shield that can provide Brings protection to the nation’s population, including the elderly. How does the
vaccine work against mutant strains? The results of the
study all show that vaccine-induced antibodies are not as effective as early Omicron strains (including BA.1 and BA.2) in blocking BA.4 and BA.5. Researchers say this may make people who receive early vaccinations and boosters more susceptible to multiple Omicron infections. Even people with mixed immunity who have been previously vaccinated and infected with Omicron BA.1 have difficulty producing antibodies that can inactivate BA.4 and BA.5. Researchers believe that these phenomena are caused by mutations in the spike proteins of mutant strains L452R and F486V.
One explanation for this phenomenon is that infection with BA.1 after vaccination may trigger the -neutralizing antibody that blocks infection. This antibody is more capable of recognizing the ancestral strain of SARS-CoV-2 than the Omicron variant. Ravindra Gupta, a virologist at the University of Cambridge, said: "Infection with BA.1 does induce a neutralizing immune response, but its scope is narrower than expected," which makes people susceptible to infections such as BA.4 and BA.5. Escape variant. What's next for
? The prevalence of
Omicron submutated strains will continue, and new mutant strains will find more vulnerabilities in the immune system. Kei Sato, a virologist at the University of Tokyo , said: "No one can guarantee that BA.4/5 will be the final strain. It is very likely that new Omicron mutant strains will appear." At present, researchers have identified the vaccine that can Multiple sites on the spike protein are recognized by antibodies, but may mutate in subsequent Omicron strains.
Another possibility is that new variants appear in the branches of the SARS-CoV-2 family tree and are different from any previous Omicron submutants. Gupta said that multiple infections with Omicron can build broad immunity to successive mutant strains, helping the immune system attack completely different SARS-CoV-2 variants. "The threshold for viral infection will be higher and higher."
A growing number of scientists believe that mutant strains, including Omicron and Alpha, may originate from chronic SARS-CoV-2 infections that last for months, during which A series of mutations that enhance immune evasion and enhance transmission accumulate. However, Mahan Ghafari, a virus expert from the University of Oxford in the United Kingdom, said that the longer Omicron and its offshoot strains dominate, the less likely it is that entirely new variants will arise from chronic infection. The ability of the
mutant strain to again evade the immune response will raise new concerns. Sato's research team found that BA.4 and BA.5 are more lethal in hamsters and more capable of infecting lung cells. An epidemiological study led by Jassat showed that the COVID-19 epidemic wave is becoming milder, but Sato also warned that this trend should not be taken for granted and that the virus does not necessarily become milder and less deadly.
It is still unclear when the next variant will appear. BA.4 and BA.5 began appearing in South Africa just a few months after BA.1 and BA.2, a pattern that has been repeated repeatedly in the UK and US. However, Althaus expects that with the popularization of immune booster shots around the world and the establishment of public immunity, the COVID-19 epidemic caused by SARS-CoV-2 will slow down.
Althaus said that one future trend of SARS-CoV-2 may be to become like the other 4 seasonal coronaviruses, with virus levels ebbing and flowing with seasonal changes, usually outbreaks in winter, and the public will be infected once every 3 years. The big question is whether SARS-CoV-2 will become milder and fade away in the long term. If it continues as it is now, it will be a serious public health problem.
Reference:
What Omicron’s BA.4 and BA.5 variants mean for the pandemic (Source: Nature)
