A Virologist Answers Our Most Pressing COVID-19 Questions
A Virologist Answers Our Most
Pressing COVID-19 Questions
There’s a lot of information and news out there about the novel coronavirus. Some of it is factual, some of it is not, and some hovers somewhere in between. Because it’s an unprecedented pandemic, we have a lot of vital questions that remain. Can children be infected? Can a person be reinfected? What’s the current progress on treatments?
So we asked Angela Rasmussen, PhD, a virologist at Columbia University who studies highly pathogenic viruses, to explain what we know now about COVID-19. And importantly, she wasn’t afraid to tell us what we don’t yet know. Rasmussen knows that self-isolation is hard, but there’s an obvious upside: If we do this right—if we band together as communities advocating for good public health practices and interventions—things will be resolved much faster.
A Q&A with Angela Rasmussen, PhD
We don’t know for sure, but genomic evidence suggests that the closest related virus that we know of is a virus naturally found in bats. Many coronaviruses originate in bats and wildlife, and coronaviruses that are pathogenic, such as the SARS and MERS coronaviruses, are thought to have originated in bats and then infected other species. We don’t know if there is an intermediate species for this specific coronavirus, but we do know that there’s a very similar and closely related virus that was found in 2017 in Yunnan, China, in a bat.
COVID-19 probably originated in wild bats, and either through direct exposure to those bats or exposure to another animal that was infected with a similar virus, it ended up crossing over into humans. One suggested intermediate host has been pangolins, an endangered scaled mammal that is widely traded on the black market for both meat and the use of its scales and body parts in some types of alternative medical treatments. Genetically similar coronaviruses have been identified in pangolins, but there is no evidence that this specific virus came from pangolins. We haven’t found the “smoking pangolin,” although it’s certainly possible that the wildlife trade in either bats, pangolins, or some other species could have been an opportunity for exposure to humans.
Other possibilities for exposure could be a bat or another animal in somebody’s home or someone who was exposed to bats in nature or to another animal carrying the virus. It’s important to note that genomic data suggests that this pandemic has been driven by human-to-human transmission after the initial animal spillover, meaning that COVID-19 cases are acquired from other people, not from animal-to-human transmission.
We’re still investigating that. One thing we do know about this virus is that it uses the same receptor as SARS. There is a protein on the outside of your lung cells called ACE2 that both SARS and the COVID-19 viruses attach to in order to get into lung cells and infect them. This ACE2 protein in our airway is what makes it possible for the virus to infect our respiratory tract. And then when the virus is expelled in droplets by breathing or coughing, it can infect another person.
We’re not yet sure why COVID-19 has spread further than SARS did in 2003. Epidemiologists use R0, also called the reproductive number, which effectively measures the average number of people who will be infected from a single person with the virus. R0 is based on infections that have already been reported, and it can change depending on how well the virus is being treated in a particular area. For example, a recent paper came out this week in Science magazine that suggested that the original R0 in China was around 2.3, meaning that every person who gets infected is going to infect 2.3 people. Obviously, there is no such thing as 0.3 of a person, so that’s why we must understand these numbers as an average. This value was prior to any kind of travel restrictions or the social distancing measures put in place by China—once those policies were put in place, the R0 lowered to around 1, and weeks later, it dropped to less than 1.
R0 is an average based on what we know, the cases that we can confirm, and it changes when behavior modifications occur or when human mobility is restricted, as we’ve seen in this case. It would also change if a vaccine or treatment became available. It’s really context-dependent, so you have to consider R0 as more of a report of what has happened than a prediction of future infections. In different populations and different countries, the way people interact and transmit infections and the demographic characteristics of the people (if they’re older or sicker) change the R0. If there are a lot of older or sicker people in one country, that can change the number of cases and the number of people who would be more susceptible to having a severe disease. R0 is not a fixed number.
South Korea has been doing the opposite of the United States and many other countries by rolling out rapid, widespread testing as soon as they had their first cases. For context, South Korea and the US had their first diagnosed cases of COVID-19 on the same day. South Korea has been able to identify a lot of milder cases. Thus, the information coming from South Korea has been tremendously valuable in trying to determine how this virus operates, how it causes disease, and what the true risk factors are. Similarly, other countries—including Singapore, Hong Kong, Japan, and China—that have more effectively controlled transmission through a variety of differently implemented testing and social distancing measures have provided road maps for containing the virus.
“We need to practice social distancing until further notice so that we don’t overwhelm our health care infrastructure. If we have overwhelmed hospitals and not enough ventilators to treat people, more people will die.”
One of the reasons we have to practice social distancing in the United States while South Korea doesn’t is because they were able to roll out testing much more rapidly and identify even mild cases and isolate those people as well as others who might have been exposed to them. The sooner we get our testing capacity up and running to test as many people as possible and identify those who should be isolated, the better—that will help us tremendously. But as of now, we need to practice social distancing until we have an accurate understanding of the prevalence of the virus in our communities so that we don’t overwhelm our health care infrastructure. If we have overwhelmed hospitals and not enough ventilators to treat people, more people will die.
We don’t know for sure, but it seems unlikely. First of all, it is possible to get a false negative on the test because the test doesn’t detect the virus for a variety of reasons. A single negative test or the resolution of symptoms does not mean that a person is no longer infected. Also, data has suggested that patients who recover from COVID-19 have neutralizing antibodies that inactivate the virus before it can infect cells. This strongly suggests protective immunity that would defend against reinfection.
Another study came out recently in which monkeys who had been experimentally infected with COVID-19 were allowed to recover and then challenged with another dose of the virus. None of them got sick or had productive infections. This suggests that their first infection produced those neutralizing antibodies and created protective immunity. The caveat here is that this study was with just four monkeys—a small sample size—and not human subjects.
For these reasons, many of my colleagues have proposed that what people are calling “reinfection” is actually “recrudescence”—a return of symptoms in patients who never actually cleared the virus.
Yes. Children are capable of being infected and can spread it to other people who are at a higher risk of severe disease. However, we don’t know why children aren’t as severely affected as older adults. People have proposed hypotheses—children’s immune systems may be different, or there may be unique exposure routes more common in children than adults—but the bottom line is nobody knows why age is a factor here. For other coronaviruses, men have been infected more often and have had more-severe disease. Older age is another risk factor, but there really isn’t enough data to suggest why. Data now suggests that men are more likely to have severe disease and more likely to die than women, but we still don’t know why that is the case.
The recent paper that suggested there were two different strains of COVID-19 in China, one more aggressive than the other, has been more or less debunked. The researchers identified these two groups of viruses as separate based on how similar their genomes were to each another, using an analysis called phylogenetic clustering. Then they looked back at the patients who’d gotten those particular strains and deduced that one group had more-severe disease than the other. However, they didn’t look at enough patients to see a significant strain difference, and genomic data suggests the virus is relatively stable and hasn’t diverged into separate strains.
There are lots of other virus sequences that can change how these groupings occur as you feed more data into the model. The other thing to consider is that there are probably a lot of undocumented cases—cases that occurred but were not recorded by epidemiologists because they were not severe enough to be tested. If somebody doesn’t go to the hospital because they believe it’s just a mild cold, they’re not going to get picked up by the public health system as a confirmed case. If you’re not able to determine all of the cases of a virus in a community, it’s very difficult to make conclusions about a particular genetically similar group of viruses being the causative agent of a more severe disease. It’s entirely possible that the so-called severe strains were also infecting people who had very mild disease but never were recognized as COVID-19 cases.
“If somebody doesn’t go to the hospital because they believe it’s just a mild cold, they’re not going to get picked up by the public health system as a confirmed case.”
Mutation is something people tend to get confused about because there are so many movies that are like: “Oh my god, the virus has mutated.” It’s important to understand what this means. Mutation occurs because the enzymes that copy the genome of the virus to replicate it don’t have proofreading capabilities, so they sometimes make mistakes. Coronaviruses are RNA viruses, meaning their genetic material is RNA instead of DNA. Coronaviruses actually have some proofreading capabilities and make fewer mistakes than other RNA viruses such as influenza or Ebola. Coronaviruses have a lower mutation rate, but they do still mutate. When many of these mutations happen, they usually have no effect whatsoever on how that particular gene functions. If there are too many mistakes in the wrong places, the virus won’t be able to replicate. Occasionally, when there is a selection pressure to keep one of those mutations because it gives the virus some kind of advantage—perhaps it makes the virus resistant to an antibody or helps it infect other types of cells—those mutations may be selected for in certain populations.
A good example of this is the influenza virus. Once drugs available to treat influenza, such as Tamiflu, started being used, we saw influenza viruses emerge that were resistant to them. The only influenza viruses that could survive the Tamiflu regimen were viruses that had randomly gotten a resistant mutation. Similar things could happen with this virus because it is an RNA virus, but we have no evidence right now that any particular mutations associated with increased severity or transmissibility are occurring.
One drug that has been suggested as a potential treatment is chloroquine, which has originally been used to treat malaria. A preliminary report showed that hydroxychloroquine, in combination with the antibiotic azithromycin, may improve clinical outcomes. One of the most advanced trials is with a drug called remdesivir. It was originally developed to treat Ebola, and it failed in a clinical trial for Ebola in the Democratic Republic of the Congo last year, so the trials were stopped. This virus is different from Ebola, so it’s possible that remdesivir could be effective against COVID-19. It’s essential to do controlled randomized trials to determine safety and efficacy before these drugs become widely available for treatment. These drugs are not without side effects, and we don’t want to waste resources pursuing treatments that don’t work. A recent report in the The New England Journal of Medicine showed that a combination of two HIV medications that had been anecdotally reported to work failed to show a significant effect in a trial of 200 patients in China. Clinical practice should be evidence-based, not justified by anecdotal reports, no matter how promising.
A vaccine for COVID-19 will likely be available in eighteen months. This has been a record pace of getting a vaccine into clinical trials because it is so urgent, but we can’t roll out a vaccine until we know that it is both safe and effective for widespread immunization.
Angela Rasmussen, PhD, is a virologist and an associate research scientist at the Columbia University Mailman School of Public Health. Her research focuses on host responses to infection with highly pathogenic emerging viruses.
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.