Does the initial amount of the coronavirus you are exposed to matter?
Let’s put that question another way: Say two similar people are exposed to different quantities of coronavirus particles. Is one of them likely to get sicker from the ensuing COVID-19 disease than the other?
If you were a scientist, how would you study this?
What you would want to do is run an experiment with a whole bunch of people, exposing some to small amounts of the coronavirus, some to medium amounts, and some to high amounts, without them or the doctors knowing who got what to avoid bias. Then, you’d check in on a regular basis. You’d see which groups got sickest, and track who died.
The problem is that doing this experiment is clearly immoral. So instead, we have to do our best by studying this subject in other ways.
We can start by looking at similar diseases. Believe it or not, we actually have done that challenge study I described above with H1N1 on a small number of people — another indication that H1N1 is significantly safer than the coronavirus. And researchers found that, yes, giving patients more disease meant it was more likely they had symptoms and more likely that they were contagious.
Of course, the studies that are not ethical for humans are frequently done on animals. In a paper published by the Infectious Diseases Society of America, hamsters were given COVID-19, then placed in a cage. A second group of healthy hamsters was placed in a cage next to them, with a fan blowing air from the infected hamsters to the healthy hamsters. Not surprisingly, 66% of the healthy hamsters got infected.
The study then compared what happened when a standard surgical mask was placed in between the cages. Only 25% of the healthy hamsters were infected.
But that’s not all. The infected hamsters in the cages blocked by a mask were less sick than the ones who were infected originally in essentially every way: Fewer of their cells were virus-ridden, their respiratory tracts were clearer, and they showed fewer and milder symptoms. This result seems to indicate that the lessened initial dose as a result of masking resulted in healthier hamsters.
The severity of sickness from original SARS in 2003 was also shown to be dependent on initial viral dose, at least in mice. From that data, along with information on who was infected in a Chinese apartment building with differing airflow, a modeling study estimated that people needed 43 plaque-forming units — a measure of disease quantity — to have a 10% chance of measurable illness, and 280 to have a 50% chance of measurable illness.
Going way back, the initial dosing hypothesis explains several discrepancies in fatality rates during the the Spanish flu pandemic of 1918.
Of course, H1N1 flu, the Spanish flu and the original SARS do not necessarily behave the same as this coronavirus, and what happens in hamsters and mice does not necessarily happen in humans. So if this dosing theory were true, we’d want to see hints of differences as it relates to this coronavirus and people.
It turns out that we do. In instances when we can tease out similar populations that likely got different initial doses of the virus, we’ve generally seen different outcomes in their disease.
The earliest such study is probably from Gangelt, the small German town in which an indoor festival led to a big coronavirus outbreak. Researchers found that those who went to the festival and caught the big dose in a superspreading event had a longer list of symptoms than those who weren’t at the festival and caught the disease secondhand.
Or take this group of more than 500 Swiss soldiers at one base. They had three companies of roughly equal demographics and an average age of 20. Two of the companies found coronavirus cases before the military decided to institute social distancing and hygiene guidelines. Despite these new restrictions, the third company did eventually see some members catch the coronavirus, but far fewer than the originally two infected companies: 15% of the third company tested positive in serological tests, compared to 62% of the originally infected companies.
Here’s the thing: Zero of the infected young patients in the third company showed symptoms. Meanwhile, in the companies that were infected before the social distancing guidelines, 102 had symptoms. It seemed like the social distancing guidelines not only prevented the disease from spreading but also prevented disease severity.
Another study looked at three coronavirus clusters in Madrid, all with similar average ages between 63 and 66 years old. About the same two-thirds of each group had comorbidities. But the first group abided by the strict isolation and social distancing protocols set in Spain, the second group frequently disobeyed the protocols, and the third group met before Spain shut down everything and therefore had no distancing protocols whatsoever. You can probably guess the trend here: The old folks who stayed socially distanced had less severe disease, even when they did get infected.
We can also compare how sick passengers got on various cruise ships. For example, on the Diamond Princess, when we knew nearly nothing about the disease, 18% of infected passengers were asymptomatic. On an Argentine cruise ship in which masks were distributed after the first passenger got sick, 81% of infected people were asymptomatic.
Prefer only evidence from America? Ninety-five percent of cases from two meat processing plants — in Oregon and in Arkansas — were asymptomatic, way higher than you’d expect. Both outbreaks happened at facilities where masks were required.
There’s looser evidence you can point to if you want to believe in this theory. One study found that while countries with high masking rates had lower infection rates than other countries, the high-masking countries had even lower death rates. This theory might also help explain the lower-than-expected fatality rate in the recent coronavirus spike in the United States. Of course, confounding factors abound there — not least of which is our improved knowledge in how to treat COVID-19 and the fact that more people will die from that spike in the days to come.
A large study released this week showed that patients with higher amounts of virus in their system in the hospital were more likely to die, though that doesn’t necessarily mean they had higher amounts of virus in their initial infection.
None of this evidence is perfect, and it all relies on comparisons that aren’t one-to-one. You can poke holes in all of these studies, and the sample sizes often aren’t big. We don’t know how the demographic of festivalgoers in Gangelt compares to non-festivalgoers, there are many differences between the Japanese cruise ship and the Argentine one, and so on.
And we should further note that getting a small dose of the virus isn’t a get-out-of-jail-free card. Even in the groups where you’d expect lesser disease doses, some people do get severely sick — just not as many.
But when you have this many studies that point to this idea, across various diseases, species and human scenarios, there’s reason to take it seriously. Further research would be nice, but we have significant evidence pointing in this direction.
If, as I believe, lower initial doses means a higher likelihood of avoiding severe sickness, that would have numerous important implications for our society.
• It would mean masks are at least somewhat protective to the wearer. The refrain of “my mask protects you, your mask protects me” is true, cute and community-oriented. It also doesn’t appeal to jerks who really only care about themselves. Masks clearly reduce viral throughput at least somewhat, and so wearing one would reduce the likelihood of severe disease for the wearer. As a result, more people would wear masks.
• It would have big implications for professionals dealing with COVID-19 patients. If you ran a hospital, a COVID-19 sick ward with multiple patients in one room might lead to riskier outcomes for doctors and patients than individual rooms.
• If you’re a person with a sick family member, it means there’s protective value in quarantining at home. Sure, you may have driven your sick spouse to get the COVID-19 test, but avoiding long and repeated exposure in the home beyond that car ride still might make a difference in the severity of any secondary infections. The guest bedroom is calling.
• It would further emphasize the time-of-exposure aspect of all of this. A quick shopping trip at a store with an infected employee is much less dangerous than an eight-hour workday shared with that same employee. Avoiding the latter scenario is key.
• It means further emphasizing outdoor activities and indoor ventilation. With those in play, the virus can linger for far less time in midair than in closed indoor environments.
• It reduces our emphasis on ending surface transmission. The amount of virus living on a surface is probably small and not going to be moved in high percentages to the respiratory area of an unsuspecting person who avoids licking surfaces in their day-to-day lives.
In short, knowing this hypothesis gives us a greater understanding of how to prioritize our day-to-day actions as we navigate the pandemic.
Whenever possible, you don’t want to encounter the coronavirus. But if you do, try to make it a small dose.
Andy Larsen is a Salt Lake Tribune sports reporter who covers the Utah Jazz. During this crisis, he has been assigned to dig into the numbers surrounding the coronavirus. You can reach Andy at email@example.com or on Twitter at @andyblarsen.