Does the first coronavirus that kicked off the pandemic still exist?
Of course you know alpha, beta and delta (in Prince-like fashion, the virus previously known as B.1.617.2).
But do you know delta AY? And epsilon, gamma, iota, lambda, mu and theta? These variants of SARS-CoV-2 have all been logged in Southern California, and dozens more versions of the virus are circulating across the globe, battling for world domination like tiny Dr. Evils in an Austin Powers movie.
So, what happened to the “original” virus? The very first one that jumped from bats or labs — or wherever — into human beings who were immunologically powerless against it, eventually leading to the deaths of nearly 5 million people and grinding world economies to a near halt?
Gone the “way of the dinosaurs, at least in humans,” said Dr. George Rutherford, professor of epidemiology and biostatistics at UC San Francisco.
“It has been displaced. Elbowed out of the way by the newer, more competitive strains,” said Andrew Noymer, an epidemiologist and demographer at UC Irvine who studies infectious diseases.
No one can say with 100% certainty that it’s gone, however, Noymer said. And Rutherford adds this caution:
“God knows what’s going on in bats.”
Welcome to this friendly tutorial on viral mutation and why your life may depend upon it.
The SARS-CoV-2 that surfaced in Wuhan, China, in 2019 was likely not the original one, researchers say. And the version that swept through the United States in fall 2020 was already a mutation of the Wuhan version. And the one that steamrolled through the United States this summer was different still.
Scientists have logged scores of versions of the virus that causes COVID-19 across the globe, and thanks to genetic sequencing, they can pinpoint which are circulating where. Sometimes, those genetic changes are of little consequence. Sometimes, they make the virus much better at infecting humans or evading treatments, and thus more dangerous.
The U.S. Centers for Disease Control and Prevention lists just the highly contagious delta B.1.617.2 and AY lineages as “variants of concern” here in the U.S., while the World Health Organization also includes alpha, beta and gamma on its “variants of concern” list.
Up and coming mutants to watch? The WHO is keeping its eye on lambda and mu.
Once upon a viral time
Scientists saw this coming.
Michael Buchmeier, an infectious disease researcher at UCI who has been studying coronaviruses for decades, takes us back some 20 years, to the original strain that sparked the SARS-1 outbreak in 2002-03.
Back then, only 12 other animal or human coronaviruses were known.
SARS-1 likely arose when two or more strains of bat coronaviruses combined and jumped to palm civets, a masked animal that resembles a raccoon and is widely sold in live animal markets throughout Asia, he said. There, the virus was amplified and adapted, and eventually infected humans. It spread widely in China, Hong Kong, Taiwan and into Canada due to travel.
The fatality rate was 10%; for those over age 50, it was close to 50%.
There’s a key difference between SARS-1 and SARS-2, however: SARS-1 infections were essentially always symptomatic, making it far easier to spot and isolate outbreaks. SARS-2 can be spread by people with no symptoms, making it much harder to stop.
So, where is that virus now?
“SARS-1 as a unique pathogen appears to be ‘extinct’ in nature, but the conditions that produced it are still existent,” Buchmeier said.
“That is, the presence of coronaviruses that are present in wild bats, particularly in the horseshoe bats common throughout South Asia and China, and the husbandry of suitable amplifying hosts like the civet cat, the raccoon dog, and now the pangolin and perhaps others capable of adapting the virus to more easily infect humans.”
Hundreds of viruses have been isolated from bats in Asia and worldwide, many of them coronaviruses that can recombine into dangerous pathogens, he said.
A paper in Clinical Microbiology Reviews, published in 2007, issued a warning: “Coronaviruses are well known to undergo genetic recombination, which may lead to new genotypes and outbreaks. The presence of a large reservoir of SARS-CoV-like viruses in horseshoe bats, together with the culture of eating exotic mammals in southern China, is a time bomb. The possibility of the reemergence of SARS and other novel viruses from animals or laboratories and therefore the need for preparedness should not be ignored.”
In 2015, another paper, in the journal Nature, warned of “a potential risk of SARS-CoV re-emergence from viruses currently circulating in bat populations.”
And, so, here we are. The precise origin of the virus that sparked the COVID-19 pandemic is still an official mystery, and may always be one. In addition to the widely embraced bat/wet market theory, there are suspicions that the virus may have leaked from a lab in Wuhan. The WHO has appointed a new, 25-member Scientific Advisory Group for the Origins of Novel Pathogens, with scientists from all over the world, to try to figure that part out.
Next up?
Genetic flexibility is an RNA virus’ superpower.
“This flexibility results in the production of a swarm of related viral ‘offspring’ at each round of replication, allowing the virus to select a genetic makeup best adapted to a given host in the form of the variant viruses we’re now experiencing,” Buchmeier said in a recent explainer.
“Mutations are always present in the progeny viruses and may be selected if there’s an advantage offered for replication in a new host species.”
The alpha variant, which was found in the United Kingdom last year, was much more infectious than the early versions. And alpha gave rise to the beta, gamma and delta variants. Delta, as we know from summer surges, is about twice as contagious as alpha.
How did delta do this? It adapted to produce as much as 1,000 times more virus in the nasal passages and upper respiratory tract early in infection, when people may not show symptoms.
That offers two distinct advantages, from the virus’ perspective: Droplets from a person’s upper respiratory tract — when sneezing, say — would spew much more virus into the air to find new hosts; and the human immune response isn’t as robust in the upper respiratory tract as it is in the lower respiratory tract, Buchmeier said.
That combination leads to many asymptomatic carriers who then spread infection to others.
So far, the variants don’t appear to have lessened the effectiveness of vaccines, but they’re straining the effectiveness of treatments.
Gamma, beta, kappa, mu and zeta variants may be moderately less responsive to some antibody treatments, while iota is significantly less responsive to some antibody treatments, according to the California Department of Public Health.
Epsilon, meanwhile, appears to result in 20% more transmission, with significantly reduced efficacy of some antibody treatments.
Mutation nation
Each new infection is a new opportunity for the virus to mutate into something else. Maybe something less troublesome. Maybe something more troublesome.
“What’s worrying me about the upcoming winter wave is not so much the variants — it’s that we need more people vaccinated,” said UCI’s Noymer. “Seventy-five percent is not good enough to protect some age groups.”
Vaccination doesn’t prevent infection, but it’s very protective against severe disease, hospitalization and death, even with the highly contagious delta variant.
“The clear message is that as long as vaccination of populations remains incomplete and clearly effective social distancing and masking are not observed, we’re very likely to see more waves,” Buchmeier said.
Will SARS-CoV-2 mutate into something more lethal still? Crystal balls are cloudy, but many experts don’t expect that to happen. They do, however, expect it to remain in circulation as part of the “human virome” — the total collection of viruses in and on the human body — for a very, very long time.
Viral variants will continue to appear, and some may be more capable of spreading.
But even if we eventually make peace with this virus — as we have with the flu — threats loom. Buchmeier said that the precursors of SARS-CoV-1 and SARS-CoV-2 remain in bats, and may provide a reservoir for future cycles of human infection.
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