The unique model of this story appeared in Quanta Magazine.

For a pathogen to make us sick, it should overcome lots. First it has to enter the physique, bypassing pure obstacles reminiscent of pores and skin, mucus, cilia, and abdomen acid. Then it wants to breed; some micro organism and parasites can do that nearly anyplace within the physique, whereas viruses and another pathogens can solely achieve this from inside a cell. And all of the whereas, it should parry assaults from the physique’s immune system.

So whereas we’re consistently inundated by microbes, the variety of microbes that enter our our bodies is often too low to get previous our defenses. (A tiny sufficient dose might even serve to remind our immune system of a pathogen’s existence, boosting our antibody response to maintain us protected in opposition to it.)

When sufficient pathogens do handle to breach our defenses and begin to replicate, we get sick. Often that is only a numbers sport. The extra invaders you’re combating off, the extra seemingly you’re to really feel ailing.

How Many Microbes Need to Enter the Body Before We Start to Feel Sick?

This varies by pathogen and is named a microbe’s “infectious dose.” Usually it takes fairly just a few, however some microbes require an extremely small variety of organisms to start out an an infection. Take norovirus for instance, the abdomen bug infamous for spreading each time persons are in shut contact and contact the identical surfaces, reminiscent of on cruise ships. Its infectious dose might be as small as 18 individual viruses, making it extremely straightforward to transmit. It can also be very hardy even exterior the physique, so an contaminated one that’s oozing the virus might depart a considerable amount of it behind—sufficient to simply infect others, even a number of days later.

What About the Concept of “Viral Load”? Is That Related?

They’re related concepts, however whereas infectious dose refers to what number of organisms will result in an an infection, viral load is an lively measurement of an infection: the variety of organisms which might be replicating inside the host. The terminology was first launched to most of the people as a part of our understanding of HIV/AIDS, and it elevated in use after the beginning of the Covid pandemic.

How Do Researchers Figure Out a Microbe’s Infectious Dose?

That’s nonetheless an inexact science. The gold-standard examine, known as a human problem examine, includes purposely giving individuals a dose of the pathogen. Unfortunately, this method is ethically difficult because it (clearly) carries a danger of significant sickness and potential long-term issues.

So as a substitute, researchers expose guinea pigs, rats, mice, or ferrets, relying on the pathogen. But it may be troublesome to immediately extrapolate animal dosage to the human equal.

Additionally, the route of an infection issues. Something that will get proper into your bloodstream will seemingly require far fewer microbes to take maintain than one which is available in by your mouth or lungs, for instance, for the reason that bloodstream permits the pathogen to bypass many host defenses. This is why, for instance, the risk of HIV infection is way increased when it comes from a blood transfusion or needle stick versus a sexual route.

A 3rd method of making an attempt to determine infectious dose is to make use of observational research, the place researchers deduce the quantity from seeing how lengthy it takes for an uncovered particular person (particularly in households or different close-contact settings) to turn into sick. As you may suspect, that is usually messy and inexact in comparison with the earlier two strategies.

Why Are the Infectious Doses of Some Pathogens Higher or Lower Than Those of Others?

We aren’t positive. It might be because of how an invader operates. Researchers have suggested that pathogens requiring direct contact with host cells tended to be simpler, so their infectious doses have been pretty low. But if micro organism assault host cells not directly (reminiscent of by secreting proteins that go on to hurt host cells), then a bigger dose of micro organism is critical to contaminate the host, for the reason that host-modifying secretions might be diluted by time and area. This concept was supported in a 2012 study that checked out viruses, fungi, and parasites as effectively. But we nonetheless want further affirmation for a greater variety of microbes.

What Do We Know About the Infectious Dose for the Virus that Causes Covid?

We’ve discovered lots within the practically 4 years because it first appeared, however a lot of it comes from animal fashions of an infection and human observational research. Most animal fashions require a excessive dose of the virus—10,000 to 1 million “plaque-forming units” (PFUs), the place every unit is sufficient to infect a cell in tissue tradition and kill it. Observational research in people, nonetheless, counsel that the infectious dose may be around 100 to 400 PFU on common, although once more this technique gives solely a really tough guideline.

These research counsel that one cause the virus is so simply transmissible is as a result of it has a comparatively low infectious dose, similar to other respiratory viruses reminiscent of RSV and “common cold” coronaviruses (and decrease than the infectious dose of most strains of influenza virus).