Imagine a glorious planet without the common cold, a twin of earth, its human population just like ours in all ways but one: Nobody has ever had a cold, because none of the more than 200 viruses that cause colds exist there.
Now drop into that world a common cold-causing coronavirus from our planet, one that typically triggers nothing more than a stuffy, runny nose. Novel on this naive twin planet, the virus ravages the elderly population and largely spares the young. Sound familiar? The hypothetical scenario isn’t a sci-fi movie plot, at least not yet, but rather a way to potentially fathom the wildly disparate age-based death rates of Covid-19, caused by the coronavirus SARS-CoV-2.
Most common colds are caused by rhinoviruses, but some are due to coronaviruses. Maybe this novel coronavirus is not all that different from those that cause colds, muses Michael Mina, MD, an assistant professor of epidemiology at Harvard T.H. Chan School of Public Health. Maybe the reason it’s so deadly for older people, Mina suggests, “is really just the complete lack of pre-existing immunity and not having had potentially hundreds of exposures to the virus over the course of a lifetime.”
“I think that’s actually a very reasonable plot… I think it’s quite possible,” says Rebecca Dutch, PhD, a virologist and professor of molecular and cellular biochemistry at the University of Kentucky College of Medicine. Dutch has heard the idea before, and credits it to Ralph Baric, PhD, professor of epidemiology and immunology at the University of North Carolina at Chapel Hill.
“Yes, I’m likely the first one who made this hypothesis,” Baric tells me. He explains: “Four contemporary human coronaviruses all emerged from animal populations 100–800 years ago. All of these viruses are mild childhood illnesses, but can cause severe disease in the elderly as they become immunosuppressed.”
Exploring the hypothesis illuminates how the human immune system works, why it works better in children, and how decades from now, if no vaccine is developed and many, many more people have died, SARS-CoV-2 could circulate routinely in humans much like other common-cold viruses.
“We will either get a vaccine, which will be great, or we will hit a point when enough of us are immune that we have a more protected society,” Dutch says in a phone interview. “So there’s a possible scenario in the future where first SARS-CoV-2 infections primarily hit kids, and the virus becomes another, what we consider cold-causing coronavirus, something we run into that’s not that big a deal.”
Viruses need us… alive and well
Human viruses, including SARS-CoV-2, can’t survive without us (or, in some cases, other mammals). They lack the ability to replicate on their own, so they thrive by worming their way into our cells and taking over the genetic machinery to make more of themselves. This activity can disrupt or kill our cells, causing the symptoms we experience, whether mild, severe or life-ending.
“The virus will benefit if it keeps its host species alive,” explains Julia L. Hurwitz, PhD, an infectious disease expert who studies immune responses and vaccine development at St. Jude Children’s Research Hospital in Memphis. “A well-adapted virus is one that co-exists with its host species.”
For its own good, the virus needs to spread easily enough to circulate nonstop in people, yet refrain from killing too many of us too quickly. In 2003, a coronavirus cousin of SARS-CoV-2 cropped up in humans. Called SARS-CoV, or just SARS, the virus made the vast majority of its victims sick so quickly and severely that they had less opportunity to spread it. Another coronavirus, MERS, emerged in 2012 and continues to circulate. But it kills a third of its victims, giving them little chance to pass the virus along, so only 2,494 people have caught MERS so far.
“I think of it like lions and buffalo,” Hurwitz says in an email. “A lion colony may survive by eating a few buffalo now and then. But if lions kill all the local buffalo, they will lose their food source and starve. In the case of SARS-CoV-2, by sparing youth, the virus can ensure that its host species will survive.”
A classic example of this developing coexistence, generated by a process called co-adaptation, actually played out among viruses and rabbits, illustrating how dangerous an unchecked a novel virus can be. In the mid-1800s, a few dozen European rabbits were introduced to Australia. You can imagine what happened next. By 1950, so overrun by hundreds of millions of crop-destroying bunnies, the government released a virus, called myxoma, known to kill these perceived pests. It worked pretty well, wiping out about 99% of the rabbits.
But a few rabbits survived, evolving resistance to the virus. In turn, the virus itself evolved to become less deadly.
“Survival of the fittest,” Hurwitz says.
Nobody predicts the novel coronavirus will destroy anywhere near 99% of humans. The worst pandemic in modern times, the 1918–19 flu, killed 675,000 Americans, less than 1% of the population at the time. But Covid-19’s one-two punch of spreadability and lethality is exactly why so much effort is going into vaccine creation.
“For SARS-CoV-2, we’re hoping that a vaccine will protect all humans, so that we do not have to wait for co-adaptation.” Hurwitz says.
Meanwhile, we’re dependent on facemasks, physical distancing and our own natural defenses.
How we fight back
The humans on our hypothetical twin world, just like us, are born with an innate immune system, which includes one army of cells that can generally destroy invading pathogens, but doesn’t do a great job against any specific germ or disease.
A separate special ops team of immune cells fuels an adaptive immune system, which creates disease-fighting proteins called antibodies that can glom onto and disable a specific virus:
B cells make the antibodies.
T cells help B cells make antibodies, and T cells can also kill human cells that are infected, thereby indirectly helping to thwart a virus.
Antibodies work only when they are selected to fit the virus well, like a key in a lock. SARS-CoV-2, like other coronaviruses, has a corona of spiky proteins that lock onto human cells. A successful antibody will, in turn, lock onto those proteins and disable them. But for now, we don’t know the extent to which people infected with SARS-CoV-2 are developing antibodies, the level of immunity they might provide, nor how long the antibodies will remain active.
We do know that the human immune system, just like the body’s other organs and systems, peaks early.
“Babies are like a shiny new car compared to an old jalopy like me,” Hurwitz says. In a healthy baby, the immune system, and all the organs, are firing on all cylinders, yet to be worn down by the miles and miles of life. Infants also get a head start on their innate and adaptive immune capabilities: an initial boost of disease-fighting cells from their mother’s cord blood and milk. If Mom had a virus before, she’ll pass some degree of immunity on to her child, Hurwitz says.
The young immune system works so well that a typical baby catches and wards off more than a half-dozen colds in their first year, a pattern that continues until around age 6. During this time and for a few more years, a child’s immune system is learning, being primed — selected and activated — to recognize invading germs and disable them. Through puberty, a child’s body produces new T cells and B cells. Then that production begins to slow, potentially slowing an immune response to a novel invader.
That’s important, because if the B and T cells activate quickly during a respiratory disease like Covid-19, “they can clear an invading virus instantly and the infection may resolve without symptoms,” Hurwitz explains. “If they take too long or can’t do their job well, a respiratory virus amplifies in the lungs. Now the immune system may cause harm. More and more cells come to the rescue, but these can block the airway and suffocate the patient” and the person dies “due to an over-exuberant immune response.”
Perhaps the rapid response is what’s protecting most children from Covid-19, Hurwitz says. Health experts believe children are contracting the virus in significant numbers — nobody knows how many — but in most cases (not all) simply not exhibiting any notable symptoms. The same goes for countless young adults, thought to spread the disease without feeling more than mild symptoms in many cases.
What if there’s no vaccine?
Given the tremendous spreadability and lethality of Covid-19, it’s “critically important” to create a vaccine, says Dutch, the University of Kentucky virologist.
But vaccines are notoriously difficult to create. While hopes are justifiably high that one will be formulated — though likely not before next year — it’s possible a vaccine will never materialize. There’s no vaccine for HIV, nor for the common cold. Also, a successful Covid-19 vaccine might not work as well for older people. Just as older immune systems don’t react as effectively to a new virus, they also don’t react as successfully to a vaccine, experts say.
And for a vaccine to be effective, people have to take it. According to a Pew Research Center survey conducted April 29-May 5, 72% of U.S. adults said they definitely or probably get the vaccine if available. That’s precariously close to the number health experts say would be needed for a vaccine to be effective across a population.
The idea is that when between 60% and 80% of a population is immune, either because they had the disease and survived or because they got the vaccine, “herd immunity” will dampen the spread to modest, manageable levels. (So far, while about 20% of people in New York City have been infected, nationwide the figure is thought to be in single digits.)
“Humanity has two choices,” Baric says.
- “Let SARS-CoV-2 burn through the population” until about 70% of people have developed some natural immunity, thereby “reducing its pandemic potential.”
- “Develop a vaccine and achieve human herd immunity the less painful way to global health and the global economy.”
Given current rough estimates of the average Covid-19 mortality rate in the United States of 0.5% to 0.8%, developing natural herd immunity would mean somewhere between 1.1 million and 1.8 million deaths — far more than any other pandemic or war in the nation’s history.
“The scale of the threat is quite large” and “potentially within that framework,” William Hanage, associate professor of epidemiology at Harvard T.H. Chan School of Public Health, says of those estimates. Hanage sees the deaths potentially playing out “over the next few years” with the worst period possibly coming this fall and winter, when he and other epidemiologists anticipate a second wave of infections that could be larger than what we’ve seen so far.
Even with a vaccine, the coronavirus won’t likely be wiped out, experts say. Chickenpox and measles offer examples of viruses that lurk despite vaccines, creating outbreaks in groups of people who are not vaccinated or whose immunity has waned.
Proactive measures matter
There’s no guarantee that the “common cold” hypothesis will prove accurate. The range of Covid-19 symptoms have proved perplexing and unprecedented, doctors say. The disease infects the respiratory system, like a cold virus, but also appears to infect the digestive system and even the neurological system. An emerging view suggests the coronavirus actually infects blood vessels, which could explain why 40% of deaths from the disease are linked to heart attacks and other cardiovascular issues.
Regardless, there are three ways to keep the Covid-19 death toll down even as the virus continues to spread, Hanage says.
First, the pandemic has taught us that preventive measures like social distancing and facemasks work, and more testing and contact tracing are vital. Hanage he hopes that knowledge will be applied moving forward.
But as states reopen their economies, the pace of new infections and deaths could vary greatly depending on the extent to which officials recommend or require preventive measures, and whether people employ those measures. Those variables are baked into nine different forecast models that predict the total number of U.S. deaths by June 20 will reach anywhere from 108,000 to 164,000.
Second, there’s the possibility of finding antiviral drugs and other therapies and treatments that improve the disease’s survival rate.
Third, Hanage says, more should be done to protect older people and those with underlying health conditions, who like the people on our hypothetical twin world, are most vulnerable. In fact, 42% of Covid-19 deaths have come in nursing homes and assisted-living centers, due not only to the fact that the residents are older but because of the close proximity that fosters rapid spread of the virus.
“We might be able to do a lot of good by coming up with better ways of protecting the most at-risk populations,” Hanage says.