In 25 months, the new coronavirus has infected 320 million people worldwide, killing 5.5 million of them.
But the SARS-CoV-2 virus could have been worse. The latest Omicron variant is highly contagious but not so fatal to vaccinated humans. The former Delta variant is usually more severe due to its tendency to attack the lungs instead of staying in the throat, as Omicron does. But luckily Delta is not spreading as fast as Omicron.
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Now imagine a coronavirus that is both deadly and very transferable. It is certainly within the realm of possibility.
To ward off a potentially worse coronavirus pandemic, a scientist from the University of Illinois at Chicago named Changchuan Yin is looking for warning signs. Genetic indications of the coming plague. But experts warned that his proposed system may be flawed because it assumes coronavirus will evolve in predictable ways.
There are plenty of coronaviruses out there in the animal kingdom; Scientists have named 46 of them so far. Anyone could jump to man - and a bunch already have. We have suffered through outbreaks of SARS-CoV-1, MERS and now SARS-CoV-2 - all coronaviruses with their characteristic peaks and tendency to cause respiratory infections.
Yin and other experts warned that it is inevitable that there will be a SARS-CoV-3 that will pass from animals to humans at some point in the near future. "We experience a new coronavirus outbreak every eight to ten years," said Kevin Saunders, director of the Human Vaccine Institute at Duke University.
Our odds of hitting the next coronavirus could get better if we see the virus coming. We could develop new therapies and vaccines and introduce public health strategies to limit the spread of the pathogen. But this means that one discovers the new virus well in advance of its leap from the original animal host to the human population.
Identifying the most likely viral sinner is a tough concert that currently involves a lot of guesswork. In a pre-print of a new study, which has not yet been peer-reviewed, Yin proposes a system for monitoring and assessing coronavirus. One that could give us the early warning we need, provided we collect and genetically sequence enough samples from bats, civets, and other coronavirus-prone animals.
Science is complicated, but it boils down to this: viruses that make peace with their human hosts - infect them, but usually do not kill them - tend to accumulate a mass of a certain kind of mutation called a "homopolymer nucleotide- repeat "or" HP repeat. "
An HP recurrence occurs when our antibodies and T cells attack a virus and the virus adapts to this attack. Each HP recurrence is a kind of genetic scar from the pathogen's fight with our immune system while the two try to enter into a kind of ceasefire.
That ceasefire makes evolutionary sense. In general, a pathogen develops to be just virulent enough to thrive and spread, but not so virulent that it kills its hosts… and itself.
"This is basic evolutionary biology, where viruses are weakened or weakened by serial passage through human or animal hosts," said Paul Ananth Tambyah, president of the Asia Pacific Society of Clinical Microbiology and Infection in Singapore. "Such are live virus vaccines - you simply infect and re-infect successive generations of animals until you select mutations that make the virus relatively harmless."
A virus with a low number of HP recurrences has probably not been exposed to humans, possibly ever.
"A low HP score suggests the virus is in a more native state," Yin explained. It's a giant red flag. The pathogen has never known humans, so it does not know how to avoid making them really, really sick or killing them. It infects human cells and just goes crazy.
So how many HP recurrences are a sign of a virus that has the potential to surprise our immune system and cause a pandemic? Six or fewer, according to Yin. "I think if a virus has lower HP ... it could be a dangerous virus," Yin said.
A coronavirus called Human-CoV / HKU1, which causes mild, cold-like symptoms, has 10 HP recurrences. SARS-CoV-2, which is obviously much more dangerous, has six. A coronavirus called SZ3, found in civets, a cat-like tropical mammal, has four of the mutations - meaning it can just be even more dangerous to humans than SARS-CoV-2. The troubling bat coronavirus HKU9-1 has only three HP repeats.
If virologists find a coronavirus with only a few HPs - keep an eye on it. Our antibodies and T cells are not ready to fight that virus alone.
But there is a possible flaw in Yin's system. As Yin points out, Omicron actually has 0.2 fewer HP recurrences than the very first strain of SARS-CoV-2 that infected humans, starting back in December 2019. Omicron evolved gradually over two years, and yet it has fewer of the revealing mutations.
Yin assumes that a human-infecting virus accumulates more HP repeats over time, but Omicron received this trend. And it underscores an important truth about coronavirus: This type of pathogen is unpredictable.
Omicron has an alarming array of about 50 key mutations, about 30 of which are on the tip protein that helps the virus invade our cells. "These big mutations that have arisen with Omicron - people said it can not happen," said Michael Osterholm, director of the Center for Infectious Disease Research and Policy at the University of Minnesota. "It was a mega leap."
If coronaviruses behaved as we expect viruses to generally behave, they would become less and less harmful over time. But Omicron confused our expectations and confused experts by being both better and worse than Delta - far more transmissible and yet somewhat less deadly. "All of us took variant evolution wrong," said Edwin Michael, an epidemiologist at the Center for Global Health Infectious Disease Research at the University of South Florida.
Omicron's lower than expected HP recurrence rate appears to be undermining Yin's design for a pandemic alert system and has made some of his science colleagues skeptical. "There are some who would disagree" in Yin's surveillance design, Osterholm said.
Yin recognizes the limits of his system. The HP recurrences "cannot directly deduce" a virulence virus in humans or, by extension, its potential to cause a pandemic. No, it's one indirectly warning of a possible ugly pathogen. "It is important for tracking, virulence assessment and controlling the outbreak of a coronavirus," Yin said. But it's not foolproof.
Given the circumstances, even a flawed system like Yins can be better than nothing. SARS-CoV-3 is coming to us, eventually. "Therefore, strict epidemic surveillance is indispensable," Yin wrote. Perhaps the risk of a false alarm, based on an imperfect search for one kind of mutation, is better than no alarm at all.
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