Gina Shaw wrote . . . . . . . . .
Alpha, delta, omicron. These Greek letters are the names that have been assigned to the mutations of the coronavirus that have occurred as the COVID-19 pandemic slogs on. SARS-CoV-2, the virus that causes COVID-19, is not the first to mutate—mutation is a key element in the spread of all viruses.
A virus is a small collection of genetic codes wrapped in a protein coat, and it has one job: to make copies of itself. But it can’t do that on its own. It can replicate only inside the cells of another, more complex organism, like an animal or a human being. When it does that in humans, it typically damages the host cells, causing illnesses such as the common cold, flu, measles, AIDS—or COVID-19.
When a virus infiltrates a host, it hacks the host’s cells, uses them to produce more copies of itself, and goes on to infect more cells. But that copying process is prone to error, and when those errors occur, they result in mutations, or variants.
Like all coronaviruses, SARS-CoV-2 first developed in animals before jumping to humans. Since its identification in late 2019, there have been many variants, but only 10 have been designated variants of interest, concern, or under monitoring by the World Health Organization.
Alpha, the first of these variants, appeared in Great Britain in late 2020, and was thought to make the virus between 30 percent and 50 percent more infectious than the original strain. The delta variant, which was initially identified in India in late 2020, was estimated to be 80 percent to 90 percent more infectious than alpha and became the dominant strain of COVID-19 in the United States by mid-2021. In late 2021, omicron overtook delta, and now almost all cases of SARS-CoV-2 in the United States are the omicron variant, says Daniel Pastula, MD, FAAN, associate professor of neurology, infectious diseases, and epidemiology at the University of Colorado School of Medicine and the Colorado School of Public Health in Aurora.
Omicron appears to be much more transmissible than any prior variant. It’s approaching the infectiousness of measles, considered one of the most infectious diseases in the world today. Though omicron has led to record numbers of cases, it appears to cause less severe disease than previous variants.
The 1918 flu pandemic also had waves that experts believe were probably driven by viral variants. “The course of that pandemic was eerily similar, with three primary waves over the course of a little more than two years,” says Dr. Pastula. The first wave emerged in the United States in spring 1918; a second, more lethal wave followed in August and September 1918. When social distancing measures were relaxed, a third wave emerged in the winter and early spring of 1919. “We weren’t able to trace viral variants back then, but it’s possible that those three waves may have been caused by different variants of that virus.”
How Variants Occur
Viruses are made of either DNA or RNA. DNA, the blueprint for all genetic information contained in an organism, replicates and stores that information; RNA converts that information into a format used to build proteins. With DNA, replication errors and damage usually resolve before they become true mutations. “Too many mutations in our DNA can develop into diseases like cancer, so our bodies have ‘proofreading mechanisms’ to prevent that,” says neurovirologist Avindra Nath, MD, FAAN, senior investigator in the section of infections of the nervous system at the National Institute of Neurological Disorders and Stroke in Bethesda, MD. “The enzymes assigned to DNA repair see the mistake and attempt to fix it.”
Those DNA proofreading mechanisms don’t always work, but they make DNA replication more reliable than RNA replication. When RNA viruses mutate during replication, there’s no proofreader to make the repair. “Most often, those mutations don’t do much of anything, or they make the virus unfit. It becomes degraded and ultimately unviable,” says Dr. Nath. “But when you have multiple millions of copies being made, some of those mutations will improve the virus’ ‘fitness’ and give it a survival advantage such as the ability to infect a host more effectively.”
This is evolution in action. “Mutations that allow a virus to replicate better are the ones that propagate more,” explains Dr. Pastula.
Some mutations make viruses less likely to spread widely, because of how they are transmitted, how lethal they are, or how they make their hosts behave. For example, the Ebola virus, which is extremely lethal, is transmitted through direct contact with blood or another bodily fluid, such as semen, feces, or vomit, when an infected person is showing symptoms. But people in the infectious stage of Ebola are too ill to come in contact with many other people.
“Ebola and another related rare virus, Marburg, kill their hosts very quickly, so they haven’t caused huge pandemics,” says Dr. Nath.
Coronaviruses—first identified in 1965 and named for their crown-like appearance—have multiple variants, most of which cause mild to moderate upper respiratory tract illnesses, like the common cold. They’re easily transmitted through the air, and people are sometimes contagious before they have symptoms or test positive. Some coronaviruses, like Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS), mutate relatively often, in ways that make them more transmissible to humans and more likely to cause severe disease.
“This is history repeating itself. We’ve seen it with SARS, with MERS, and with other similar viruses before,” says Beau M. Ances, MD, PhD, FAAN, an endowed professor of neurology at Washington University in St. Louis. “Sometimes viruses hit and stick and start spreading, and that’s when pandemics occur. The same thing happens with influenza: There are different variants and strains, which is why we have a new flu vaccine every year. We’re trying to prime the immune system to recognize the things that it is most likely to be exposed to.”
Proactive Strategies
One of the best ways to prevent the development of future variants is to block them from moving from one host to another, where they can make more copies. Vaccines eradicated the smallpox virus worldwide and the polio virus from the Western Hemisphere. In the United States, measles had been considered eliminated thanks to vaccinations, but cases began to increase beginning in 2008 as a result of declining vaccination rates.
“Vaccines work,” says Dr. Ances. “But if not enough people get vaccinated, you can have outbreaks, wildfires that will start smoldering. When a virus is very contagious, like measles or the omicron variant of COVID-19, and there’s not enough of a firewall around it, that virus will spread quickly.”
Herd immunity occurs when a significant portion of a population becomes immune to an infectious disease, decreasing the risk of spread. “You really have to have many people vaccinated to reach herd immunity,” says Dr. Ances. The threshold varies with different diseases based on how infectious they are. Measles and the omicron variant, for example, spread so easily that about 95 percent of the population needs to be vaccinated to achieve herd immunity.
Compared with previous variants, omicron has evolved to be more resistant to current vaccines, but vaccines can still prevent those infected from developing severe illness. The latest data from the CDC, released in mid-February, indicated that vaccine effectiveness against hospitalization was 91 percent during the first two months after a third dose and remained high, at 78 percent, four or more months after a third dose of one of the two mRNA vaccines (Pfizer and Moderna).
Researchers are now working to create vaccines that can protect against multiple possible variants. “We’ve learned a similar lesson in managing HIV,” says Dr. Nath. “We found that if we use just one antiviral drug against HIV, that produces more resistant forms of the disease, while triple and quadruple therapies can attack the virus at multiple points in its life cycle. These HIV treatments are not vaccines, but the concept is the same: If a virus mutates rapidly and develops resistance, you need many ways of attacking it. It’s possible the situation with COVID-19 will be the same.”
But vaccines are just one form of protection against any kind of viral variant. “Through hundreds of years of research, we have realized that controlling the spread helps control infections,” Dr. Nath says. “For example, mosquito netting and other forms of mosquito control are essential to preventing the spread of mosquito-borne diseases like West Nile virus and chikungunya [a viral disease occurring mainly in Africa, Asia, and India that causes fever and severe joint pain].”
Many viruses, including Ebola, rabies, Zika, African swine fever, and SARS-CoV-2, have moved from animals to humans through a complex biological process called spillover. And increasing destruction of animal habitats means that humans and wildlife are coming into contact more frequently, creating more opportunities for spillover. “We have to understand how to interact with the environment, nature, and animals in a way that doesn’t let viruses jump to humans,” says Dr. Pastula. That could require measures like restoring habitats for animals, such as bats, that have often been sources of spillover, locating them well away from populations of domestic animals and people.
Public health–minded habits such as handwashing, isolating when sick, and wearing masks, as well as improved ventilation in indoor spaces, are also key. Flu cases and deaths worldwide dropped to unprecedented lows in 2020 and 2021 because of such actions, according to an editorial in JAMA Network in August 2021.
“It’s amazing how often, before the pandemic, we went to work when we were sick or sent kids to school sick,” Dr. Pastula says. “I’m hopeful that what we’ve learned from this pandemic can help bring about a cultural change, not only among individuals but among employers. Don’t penalize employees for staying home when they’re sick. Make sure to offer flexible sick leave. We don’t want people coming in when they’re ill and contagious and infecting their co-workers.”
Antiviral medications are also important. “Developing broad-spectrum antivirals that can target resistant forms of viruses is important,” Dr. Nath says. “We need a multipronged attack on viruses: managing and preventing the spread, instituting public health efforts like masks and social distancing, providing vaccines, and developing treatments. No one approach is going to do it alone.”
Source: Brain&Life