An Infectious-Disease Researcher Answers Our Latest COVID Questions
An Infectious-Disease Researcher Answers Our Latest COVID Questions
January 27, 2022
A full two years into the pandemic—and a few hundred visits to the New York Times COVID map later—we have a lot more knowledge than we did at the start about the virus we’re up against, how best to protect ourselves from it, and how to treat the infection it causes. Still, there are plenty of unknowns and plenty of disagreements over how we move forward.
In late 2020, physician-scientist Otto Yang, MD, joined GP for a podcast conversation to answer our questions about the virus as we knew it then. (At the time, GP was enrolled in a clinical trial run by Yang and sponsored by the NIH.) He’s back to give us the latest updates as we face Omicron and to level with us about what might be coming our way next. Listening to Yang talk is refreshing: His answers are clear and honest, and he helps us understand on a deeper level the virus, variants, vaccines, and complicated issues like long COVID.
(A note: Yang’s lab, which studies new therapies and vaccines for infectious diseases including HIV and COVID, largely relies on donations to do its research. You can donate to the Shandling Biomedical Future Fund to support Yang’s work.)
A Q&A with Otto Yang, MD
Since then, we’ve been through Delta, and now there’s Omicron. We’ve learned that the virus is continuing to adapt to being in humans and that those adaptations are tending to make the virus more transmissible than it ever was before. And those adaptations can make the virus either more deadly or less deadly. In the case of Delta, it’s more deadly. In the case of Omicron, it’s less deadly. It’s unpredictable at this point which variants will take off, so it’s hard to know what to expect for the future.
A lot of people are jumping on this bandwagon that Omicron is milder and therefore it’s a good thing. But that’s not what we’re seeing in the hospitals. The effect of Omicron being milder but more contagious is complex, and it’s all about context. One thing to point out is that current research estimates that Omicron may be about as lethal as the original strain of the virus, even though most of us think about it as milder. It’s just that the subsequent strains, particularly Delta, have been deadlier. So we’ve become a little blasé about how lethal it is, thinking that Omicron is something relatively harmless, like a flu or cold.
Here’s the math: If Omicron is two or three times as contagious and half as deadly as Delta, it’s not an advantage overall. Because that means that just as many people may die overall, even if the risk is smaller for an individual.
One of the big challenges of this pandemic has been personal interest versus society-level interest. That’s what’s been a problem with Omicron. On a personal level, perhaps it is good news, right? If you’re vaccinated and Omicron is somewhat milder, your personal level of risk really does go down. If I’m vaccinated and in good health and I don’t have any immune problems, I can feel confident that if I get infected, I’m probably not going to get very sick.
Omicron has mutated from the original virus—the one the vaccines are targeted against—enough that the vaccines probably won’t prevent me from getting infected. The vaccines are targeted against the original strain, not against Omicron. And while they are still preventing people from getting very sick, they’re no longer preventing people from getting infected.
It’s a little socially complex, right? For those in a good position in terms of health and vaccination, on a personal level, it is lower risk. But for those who aren’t in that position, it’s much worse. There are many people in our society who either won’t get vaccinated or can’t get vaccinated—or are vaccinated but their immune systems don’t respond to the vaccine, like lung transplant patients whose medications keep the vaccines from working. Those people are paying the price—a heavy price, as we are seeing in our hospitals.
Then, of course, the indirect impact is that the hospitals are once again overfilled with people who are sick with Omicron. And that affects healthy people, too. Because if you get in a car accident or develop cancer suddenly and you urgently need hospital treatment, hospitals are not going to be as able to provide care. And god forbid you need an ICU bed—the ICUs are just packed.
The really big change—and the reason Omicron is so much more contagious—is probably that there is more infectious virus being expelled when people breathe or talk. That change has made this virus into what doctors classically call an airborne infection.
“The fact that Omicron now produces so much more virus in people’s respiratory tracts means that now even the very small droplets that can float around in the air probably have enough virus to cause infection.”
In the beginning, the original strain was mostly considered a droplet infection, meaning that only the larger respiratory droplets that don’t float in the air had enough of the virus to pass it on, so you had to be close to somebody to get infected. The smaller particles that float through the air probably didn’t have enough virus to be contagious in most circumstances. The fact that Omicron now produces so much more virus in people’s respiratory tracts means that now even the very small droplets that can float around in the air probably have enough virus to cause infection.
What that means is you should avoid being in closed spaces where there’s not good air circulation. Being indoors with crowds is very risky. If you have to be indoors—to go get your groceries or whatever—an N95 (or similar) mask is probably the best one to wear right now. A cloth or surgical mask does not have pores small enough to filter out the tiny aerosol droplets. N95 masks are designed exactly for that purpose: to filter out the really tiny droplets that can float around in the room for minutes or even hours.
Being outdoors is still not that big of a risk, especially if you stay separated enough that the bigger droplets can’t get to you—that’s six feet or so. Just the fact that you’re outdoors means those little droplets can diffuse away very fast, so the risk is much, much lower than being inside. It’s probably okay to be doing outdoor events.
It’s a mixture of expected and unexpected things. What’s consistent with other viruses is how the virus jumped into humans and what makes it able to cause a pandemic. The first thing to know is that viruses don’t have all the parts that they need to make copies of themselves, so they have to use host cells in order to replicate. It’s like they turn that host cell into a virus factory. To do that, they have to be able to interact with the proteins in that host cell. And the host proteins they use to make their various virus parts vary from species to species.
Generally, when a new virus enters into humans, it comes from an animal. (Viruses don’t just appear out of nowhere.) But it’s not easy for a virus to jump into humans from an animal. First, the virus has to get into the cell, which usually involves binding to a receptor. In this case, it’s the ACE-2 receptor. Receptors will vary from species to species, so the most common thing that happens if a person is exposed to a virus from another species is nothing—because the virus can’t use human receptors or can’t use their cell proteins to replicate itself. It’s adapted to work best in the cells of its original host. Occasionally, a virus will be able to use human proteins and get into human cells.
“This novel coronavirus hits this sweet spot where it’s deadly, but it’s not so deadly that it can be easily stamped out.”
That’s what happened in the biggest pandemic in recent history before this one: HIV. HIV originally came from chimpanzees, and chimpanzees are very similar to humans genetically, so the virus was able to jump species because human cells were similar enough to the chimpanzee ones. Unfortunately for us, the virus was adapted for chimpanzees, where it’s a mild infection with few or no health consequences. In humans, it was new, and it became a deadly infection. It was able to interact with human proteins and grow in human cells.
Another virus that has jumped into humans is Ebola. The Ebola virus is adapted to its host animal—bats—and it’s not a harmful infection in those animals. In humans, it is very harmful. But Ebola has not become a pandemic because the virus is too aggressive. People die too quickly. By the time they’re contagious, they have serious symptoms. So it’s been relatively easy to stamp out Ebola breakouts.
This novel coronavirus hits this sweet spot where it’s deadly, but it’s not so deadly that it can be easily stamped out. It happened to be able to deal with human proteins, grow in human cells, and spread from person to person before it kills them. In that way, this virus is what you would expect: It’s deadlier than in its original host.
What’s been unpredictable are the twists and turns of how these different variants come up. And the other unusual part is that with this virus, people are contagious before they have any symptoms. For respiratory viruses, that’s pretty much unheard of. This is the first virus we’ve seen that has that property.
Contagiousness and lethality do not necessarily go hand in hand. Delta was more contagious and more lethal than the original virus, and Omicron has been more contagious and less lethal than Delta. The next variant that could pop up could again be more lethal. It’s premature to say the virus would become less lethal over time in the near future. Because we don’t know, we shouldn’t let down our guard, accept it, and get infected.
The other prediction I would make is that over time the variants will slow down and maybe even stop. The reason these variants are coming up is because the virus is still adapting to optimize its spread in humans. It was optimized to spread in some other animal species before us, and these variants we’re seeing on a large scale have evolved in a way that allows them to interact better with human cells and the human ACE-2 receptor. So if natural selection favors these mutations that allow the virus to grow better using human cells and ACE-2 receptors, at some point it’s going to reach its optimum for spreading in humans. At that point, the variants are probably going to slow down.
There will not be herd immunity in the sense that people hoped for in the beginning. That’s straightforward to predict at this point because the immune response to this virus doesn’t last a long time, and so people can get reinfected. That’s also true with the vaccines; the immunity from the vaccines doesn’t last long. Herd immunity depends on enough people being immune concurrently from infection to stop the virus from spreading, but that won’t happen if immunity doesn’t last.
That’s not surprising: The four common-cold coronaviruses that circulate all the time have been doing so for a very long time, and there is no herd immunity against them. However, we can expect that as more and more people get the virus, there will be some level of persisting immunity in the population. So even though there won’t be herd immunity that stops the virus from circulating, infection may become milder over time because most people will have some immunity from previous infections and vaccinations.
The vaccine does two things (I’ll oversimplify it a little bit): It makes antibodies, and it makes T cells. The antibodies are like the front gate. They slow down or reduce the amount of virus that gets into the body. If you’re lucky, the antibodies will slow the virus down to the point that the virus doesn’t get established in your body. But once the virus gets past the antibodies, they don’t help anymore. Then, it’s all T cells. T cells, particularly so-called killer T cells, are what keep you healthy or keep you from dying if you do get a viral infection.
Antibodies are very, very specific to one spot on the spike proteins for the virus they protect against. And that’s because antibodies work by blocking the interaction of the virus with the ACE-2 receptor. So the virus has to bind ACE-2 to get into a cell, and antibodies bind the virus to block that from happening.
The mutations defining these new variants are changes that affect how the virus interacts with ACE-2. They are exactly in that area the antibodies would need to bind to stop the virus. And because the antibodies produced by the vaccines are directed specifically to the original-version virus, not the variants, the antibodies don’t fit as well to the variants as they did to the original virus and don’t work as well as a result. That’s why there are so many breakthrough infections with Delta and now Omicron.
On the other hand, T cells don’t need to work on just a small area the way antibodies do. They can work by recognizing any part of the spike protein. That’s why the T cell protection you get from the vaccine has really not been affected by these variants: Omicron is still 97 percent unchanged from the original strain, so the T cells still work. That’s why we’re seeing vaccinated people getting breakthrough infections but not often suffering very severe illness—because the T cells, the second part of that equation, are still working fine.
It is going to be important to keep up with the virus. Creating or adjusting a vaccine to account for multiple strains of a virus or bacteria is not unusual. We need a new flu vaccine every year because there are so many changes to the virus every year. Pneumonia vaccines cover twenty-three strains of the pneumonia bacteria. The current polio vaccine covers three strains of the poliovirus.
It shouldn’t be a big deal to adjust vaccines to deal with these virus variants. New versions of the vaccine would only need to be slightly tweaked from the originals in order to work optimally—Omicron, for example, is about 97 percent the same as the original virus—and that’s not difficult to do with these RNA technologies. I’m not sure what the delay has been. It could be coming from vaccine companies or the FDA. If we can get vaccines that keep up, we could have a big impact on slowing the spread of the virus because the antibodies would work again.
It’s been a very tricky matter. First of all, it’s hard to define exactly what long COVID is. People haven’t fully agreed on a definition. It probably is not one single disease entity. There are likely multiple forms of long-term side effects from having had COVID. Some of it may be muscle, nerve, or brain damage from the infection itself: Damage has been done, and there are symptoms from that damage. And then some of it may be that the immune system was so revved up during the initial infection that it hasn’t returned to normal, so it’s causing ongoing inflammation in the body that is causing symptoms.
It’s interesting that in some studies of COVID, we’ve found the risk of getting long COVID doesn’t seem to be associated with how severe the original, acute COVID symptoms were. Someone who has a very mild infection that is not much worse than a cold can get long COVID. Somebody who was in the ICU for their COVID symptoms may not get long COVID.
While there’s ongoing research on long COVID, right now there’s no known way to predict it or reliably treat it. That’s another reason to try not to get COVID. Death is not the only bad outcome.
While COVID is generally a much milder disease in children and the risk that children face is much lower, it’s not entirely benign either. Some kids who get COVID get something called MIS-C: multisystem inflammatory syndrome. It can be very severe, require long hospitalizations, and cause heart and nerve damage. Some children—about fifty in the US alone—have died from MIS-C.
There’s a difficult balancing act here. I have a three-year-old. Do I sacrifice her social development and keep her home? Or do I let her go to daycare so that she can have friends and socialize and start learning new things, knowing the risk? There are no right answers. If the numbers are very high in your area, keeping the kids out of school might be a good idea for now. If you’re in a school where classroom density is low, most people in your region are vaccinated, and case numbers are low, then it probably favors sending your kid to school. It’s a personal decision, and not an easy one.
I think it is. I haven’t gotten it, and I’ve been seeing Omicron patients. We still know how COVID spreads: through respiratory droplets in the air. The biggest risk is being close to people and getting the big droplets. If you avoid crowded indoor spaces and you properly wear an N95 or similar mask when you must be inside, you definitely can protect yourself from getting it.
Personally, I’m dining outdoors and seeing friends outdoors. I’m not dining indoors. When I go to get groceries, I wear an N95 mask, and I try to minimize trips. Instead of making a trip every two days to buy stuff for a couple of days, I try to take a trip once a week and buy a lot at once. You’re probably not going to get COVID by touching something at the grocery store and then not washing your hands—this is a fragile virus that does not efficiently spread from contact. But it’s still a good idea to wash your hands often and be careful with touching because other viruses do spread very efficiently that way.
“Everyone really should get boosted if possible. There’s good evidence that the boosting can prevent you from getting Omicron.”
And I’ve been boosted. Everyone should get boosted if possible. There’s good evidence that the boosting can prevent you from getting Omicron. What I told you about the antibodies is true: The antibodies aren’t directed against Omicron, so they don’t work against Omicron very well. But there’s an interesting twist to that: If you get a booster, it does two things. It brings your antibodies back up to high levels. Very high levels of antibodies do work against Omicron. And the booster also improves the quality of those antibodies, so the antibodies that are there have more activity against Omicron. In fact, a booster may stop you from getting Omicron at all.
I’m hoping to raise public awareness and get donations for my research at UCLA, which includes COVID research. You can learn about the Shandling Biomedical Future Fund and its goals, and at the bottom of the page, there’s a link to donate. (The site is for UCLA as a whole, but the donation will be tagged specifically for the fund.) UCLA is nonprofit, so donations are tax deductible, too.
Otto Yang, MD, is a clinician, a professor, and an infectious-disease researcher at UCLA’s David Geffen School of Medicine. Yang specializes in developing immune therapies and vaccines for HIV and other viral infections, including COVID-19. His research is funded by the Shandling Biomedical Future Fund. He went to medical school at Brown University and completed his fellowship at Harvard Medical School.
This article is for informational purposes only, even if and regardless of whether it features the advice of physicians and medical practitioners. This article is not, nor is it intended to be, a substitute for professional medical advice, diagnosis, or treatment and should never be relied upon for specific medical advice. The views expressed in this article are the views of the expert and do not necessarily represent the views of goop.