What we need to understand about asymptomatic carriers if we’re going to beat coronavirus

ProPublica’s health reporter Caroline Chen explains what the conversation around asymptomatic coronavirus carriers is missing, and what we need to understand if we’re going to beat this nefarious virus together.

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SOURCEProPublica

In the early days of the coronavirus outbreak in the U.S., around the last week of February, I joked to a colleague that maybe now, finally, people would learn how to wash their hands properly. My remark revealed a naive assumption I had at the time, which was that all we needed to do to keep the novel coronavirus contained was follow a few simple guidelines: stay home when symptomatic and maintain good personal hygiene. The problem, I thought, was that nobody was following the rules.

In the past few weeks, however, more and more reports have emerged to challenge my neat assumptions. Seven out of 14 NBA players, coaches and staff who tested positive didn’t have symptoms when they were diagnosed, The Wall Street Journal reported. The U.S. Centers for Disease Control and Prevention issued a case study on a nursing facility in King County, Washington, where 23 residents tested positive for COVID-19, and it found that 13 reported no symptoms initially. Sixty singers went to rehearsal and followed all the rulesaccording to the Los Angeles Times — nobody hugged, shook hands or appeared ill — yet three weeks later, 45 were diagnosed with COVID-19 or had symptoms of the disease, and two have died.

With articles about “silent spreaders” and “stealth transmission” flying across the internet, friends were starting to text me: Was it still OK to go for a walk with a friend, even 6 feet apart? Or should all interactions be avoided? Should we start wearing masks to the grocery store? At the same time, my colleagues were scrutinizing guidelines at various workplaces and agencies we cover: The New York City Fire Department told workers on March 19 they were to come to work, so long as they had no symptoms, even if they had had “close contact with someone who is a known positive COVID-19 patient,” according to a document obtained by ProPublica. Was that policy wise?

I decided to dive into the available data. What I discovered is that not only can people be infected and experience no symptoms or very mild symptoms for the first few days, but this coincides with when the so-called viral load — the amount of virus being emitted from an infected person’s cells — may be the highest. That makes the virus a truly formidable opponent in our densely packed, globally connected world. We’re going to have to be smarter than this virus to stay on top of it.

What does asymptomatic really mean?

Let’s start with the basics. Dr. Maria Van Kerkhove, head of the emerging diseases and zoonoses unit at the World Health Organization, told me that the WHO so far has found few truly asymptomatic cases, in which a patient tests positive and has zero symptoms for the entire course of the disease. However, there are many cases where people are “pre-symptomatic,” where they have no symptoms at the time when they test positive but go on to develop symptoms later.

“Most of the people who were thought to be asymptomatic aren’t truly asymptomatic,” said Van Kerkhove. “When we went back and interviewed them, most of them said, actually I didn’t feel well but I didn’t think it was an important thing to mention. I had a low-grade temperature, or aches, but I didn’t think that counted.”

The WHO sent a team to China and visited community centers, clinics and hospitals, and transportation hubs. Through their data collection, the team found that about 75% of people who were initially classified as “asymptomatic” went on to develop symptoms, she said. This matches up with the CDC’s findings at the nursing facility in Washington. Of the 13 positive patients who initially reported no symptoms during testing,10 later developed symptoms.

But ultimately, the only way to really find out how many asymptomatic COVID-19 carriers are out there would be to conduct blood tests across large swaths of the population to look for antibodies, which are a type of protein that provide evidence that a person’s immune system did battle with the coronavirus. Tests that can look for these antibodies are now being developed in several countries.

For the purposes of containing the outbreak right now, however, Jeffrey Shaman, a professor of environmental health sciences at Columbia University’s Mailman School of Public Health, says the focus on asymptomatics is a bit of a red herring.

“In some sense, symptomatic versus asymptomatic isn’t really the appropriate dividing line” for us to be focusing on, he said. “The appropriate dividing line is documented versus undocumented infection.”

What Shaman means by “documented” is people who are identified as being infected, either because they were sick enough to go seek care or were tested through contact tracing, which is when public health officials track down all the contacts of someone who tested positive. The “undocumented” could be people who have symptoms but didn’t get tested, because of lack of access to testing, dislike of doctors or sheer stoicism — or more concerningly, people who had no symptoms or such mild symptoms that they decided to just carry on with their daily lives.

“Maybe they pop some ibuprofen, but still go to work, still get on public transportation, still do all the things we normally do, and the consequence of that is those people with mild infections — as well as if they’re truly asymptomatic — are taking the virus out into the community, and they’re spreading it far and wide,” Shaman said.

Shaman and colleagues published a study in the journal Science on March 16 in which, using a statistical model, they estimated that 86% of all infections in China were “undocumented” prior to Jan. 23, when Chinese authorities cut off Wuhan, canceling all planes and trains leaving the city. This would help explain the rapid spread of the virus across the country, they said, concluding that their findings “indicate containment of this virus will be particularly challenging.”

The disease IS spread by liquid “droplets.” But the human body has lots of ways of creating these minuscule, virus-laden flecks.

If there are thousands of asymptomatic or pre-symptomatic people out in public, how are they transmitting the disease, if they’re not coughing or sneezing? After all, as I’m sure many of us have heard, this disease spreads primarily via droplets.

The WHO’s Van Kerkhove said research so far shows that liquid droplets are necessary to transmit the virus, and they need to go from the infected person’s mouth or nose into someone else’s eyes, nose or mouth. (People can also get infected if they touch a contaminated surface where a droplet has fallen onto and then touch their eyes, nose or mouth.)

But sneezing and coughing aren’t the only ways droplets get transmitted.

“People clear their throat,” Van Kerkhove pointed out. “Some people spit when they talk.” I winced.

Angela Rasmussen, a virologist at Columbia’s Mailman School, provided more vivid descriptions for my mental tableau. “Droplets are not necessarily huge, like globs. We release respiratory droplets when we speak.”

“When you go outside and it’s really cold out and you see your breath fog — that’s respiratory droplets,” she said.

This doesn’t mean that the coronavirus is being transmitted as an “aerosol,” which is the term that many researchers use when virus particles remain suspended in the air for long periods of time. That applies to the measles virus, for example, which is why that microbe is so incredibly contagious.

However, it does mean that if you’re standing right next to someone who is infected and they’re talking to you, or, say, if you’re in a room full of singers who are projecting their voices in an enclosed space, there are going to be droplets in the air, and yes, you could inhale them.

What’s still fuzzy is exactly how far one needs to stand in order to be ideally protected from coronavirus droplets. The WHO says 1 meter, or 3.2 feet. The CDC says 6 feet. Lydia Bourouiba, a fluid dynamics expert at the Massachusetts Institute of Technology, published a paper last week that said that “peak exhalation speeds” can create “a cloud that can span approximately 23 to 27 feet.” Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, later called the study “terribly misleading.”

While the exact measurements are being debated, the experts I spoke to said that if you have to leave home, staying outdoors is the safest bet, since open air can help to “dilute” any potential microbes that reach you. While, of course, this isn’t free of risk, one has to balance that risk against, for example, the mental and physical health benefits of going out for a run. So keep going out to exercise, the experts said. Maintain a 6-foot distance, at least.

You’re likely most infectious right after you contract the virus, possibly before you know you’re sick.

So we have a virus that can transmit from one person to another, standing a few feet apart, in the course of conversation, perhaps helped along by a few errant throat clearings, while the infected person either didn’t have any symptoms yet or had a few minor body aches they didn’t think much of.

That’s already a recipe for a bad outbreak, but this coronavirus has another aspect that’s helping to amp up its contagion factor. Studies are now finding that people are shedding more virus during early stages of the disease rather than the later stages.

The term “shedding” may bring to mind my cats, whose fluff seems to evade even my most ardent of vacuuming attempts, but it doesn’t actually mean that virus particles are being emitted off patients’ skin in an infectious cloud. It’s a term used by researchers measuring the amount of viral RNA from someone who is infected, from a sample gathered via a method like a throat swab.

study of 94 patients in Guangzhou, China, found “the highest viral load in throat swabs at the time of symptom onset” and concluded that meant that patients would be most infectious right before or at the time when symptoms started appearing. That study was published online as a pre-print and has not yet been peer-reviewed, but lead author Dr. Gabriel Leung, dean of medicine at the University of Hong Kong, said it has been accepted for publication in the journal Nature Medicine. Another study, also conducted by researchers in Hong Kong and published in the journal Lancet last week, found that viral load, this time in a saliva sample, was “highest during the first week after symptom onset and subsequently declined with time.”

The authors of the Lancet paper noted that this profile contrasted with COVID-19’s coronavirus cousins SARS, where the peak viral load was around 10 days, and MERS, at the second week after onset of symptoms. COVID-19’s “viral load profile” actually appears to be more similar to the flu, the authors wrote, which also “peaks at around the time of symptom onset.” Viral load is thought to correlate with a patient’s ability to infect others, and when the peak comes later on during the course of disease, it’s more likely that a patient will have already sought care, been tested and either started treatment or gotten instruction to stay isolated.

The high viral load early on in the course of disease for COVID-19 patients “suggests that [the virus] can be transmitted easily, even when symptoms are relatively mild,” wrote the authors of the Lancet paper. This finding “could account for the fast-spreading nature of this epidemic.”

All of this makes it extra hard to set workplace standards.

Against this wily virus, it’s difficult to set comprehensive guidelines. “What we recommend is if you’re feeling unwell, stay home,” said the WHO’s Van Kerkhove. That sounds simple, but after our conversation, I was doubtful as to how to carry this out. What counts as “unwell”? If I wake up with a scratchy throat, how can I tell if that’s seasonal allergies or a potential early COVID-19 symptom? When’s a headache just a headache?

I’m fortunate that I’ve been able to work from home for the past month and rarely need to leave my apartment. But many aren’t that lucky. My colleague Michael Grabell recently wrote about workers in the meatpacking industry who often don’t have paid sick days and work shoulder-to-shoulder. Even if on paper, their employers say they “don’t want team members who feel sick to come to work,” it’s unclear what counts as “sick” enough that they won’t get in trouble.

I asked the CDC, given what its own studies are finding on asymptomatic transmission, how workplaces are supposed to set policies, and the agency directed me to this page, which says: “Employees who have symptoms (i.e. fever, cough, or shortness of breath) should notify their supervisor and stay home.”

Like the WHO instructions, that really doesn’t seem to address the questions posed by a virus that can be spread by people before they experience symptoms. But it’s also understandable why agencies are setting guidelines around black-and-white things like fevers (which are objectively measurable) and coughs (which is also a binary call). It’s pretty much impossible for the CDC to weigh in all the possible symptoms that this coronavirus might cause, especially the more subjective ones like mild headaches or fatigue, even if they could turn out to be early COVID-19 symptoms for some.

Dr. Raphael Viscidi, a professor of pediatrics at Johns Hopkins School of Medicine who worked on a vaccine for the SARS coronavirus, notes that there are different standards being asked of the general population and of essential workers, for good reason.

“On a population basis, the message has to be strong, it has to be consistent, and it has to be repeated: We have to exercise maximum social distancing,” he said. “But then you start saying, well, what about the people that have to go to work?”

Hospitals that are short-staffed don’t have the luxury of having conservative policies and telling staff to stay home and quarantine themselves before they exhibit symptoms, even if they’ve been exposed to someone who has a confirmed infection.

“The problem is we need the health care responders, because we have to care for the critically ill, so there’s probably going to need to be an exception,” said Columbia’s Shaman. “And they’re going to have to rely on their PPE, the personal protective equipment, to prevent them from spreading it to other people.”

Viscidi acknowledged: “You are giving one message to the people you’re asking to work and another message to the general population. For sure, some people are forced to take slightly greater risks.”

We’ve got to fight this virus with all we’ve got. Here’s how we do that.

Since symptoms-based policies alone cannot be perfect, we need to turn to other strategies to catch the people who slip through the gaps presented by a broad “If you’re feeling unwell, stay home”-type recommendation.

In recent days, there’s been a new enthusiasm for masks, with many calling for widespread use among the general public. The idea there is that masks could help prevent droplets from traveling far, particularly from an asymptomatic person who doesn’t yet realize they’re infected.

Leung, from the University of Hong Kong, is a fan of this idea. “Wear a mask, preferably universally in public spaces,” he said, when I asked him how to solve the problem of asymptomatic transmission. But he also pointed out that there’s a practical hurdle to this plan — “Of course this is not possible for some places where there are mask shortages even for hospital workers,” which would be most of the United States.

After months of saying that healthy individuals should not wear masks, administration officials are now considering guidance for much broader, communitywide use of masks, Fauci told CNN on Tuesday.

In an absence of an abundant supply of masks — which, by the way, also need to be worn properly to provide protection — both the WHO and CDC stressed how important social distancing was. “COVID-19 spreads between people who are in close contact with one another,” the CDC said in a statement. “That’s why the CDC recommends staying at least 6 feet away from other people, so someone doesn’t spread the disease if they are sick or are exposed through contact with someone who is sick.”

Not only can social distancing protect you as an individual, but the better the general public is at adhering to these guidelines and staying at home, the less virus will be circulating in the public to potentially infect paramedics, grocery store workers and public works employees and other essential staff.

For workers who absolutely have to turn up in person, Columbia’s Rasmussen explained to me that dose also matters. We understand this instinctively. If someone infected sneezes straight at you from a foot away, splattering your entire face with wet gunk, you’re going to feel more nervous about your likelihood of getting sick than if a single virus landed in your mouth.

“It’s not always as simple as you come into contact with a single infectious particle and you’re going to be infected,” Rasmussen said. “You usually have to have a certain number of those particles in order for them to evade the immune system, get past the mucus barrier that’s in your nose and throat, come into contact with a cell that has the virus receptor on it, and then get into the cell and start replicating.”

So increasing the chance that the virus will be “diluted” is important. That means workplaces like meatpacking factories and delivery warehouses should do whatever they can to space out their workers, and not have meetings en masse in indoor spaces, where droplets are likely to persist and don’t have a chance to be carried away by wind. And of course, companies should have generous sick leave policies, so workers can err on the side of caution if they do feel unwell.

And let us not forget about testing. Testing is critical, because it can let people know if they’re sick before symptoms emerge and prompt them to self isolate. At a big picture level, testing helps public health officials know where the disease is spreading and better allow them to direct resources and responses efforts.

TI was wrong to ever think that curbing the novel coronavirus could be simple. It is truly a dastardly bug. But I’m confident we can be smarter. Even if COVID-19 doesn’t vanish and becomes a seasonal illness, if we give it all we’ve got, I think we stand a good chance of getting this stealthy virus under control.

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