Thread by @ukhadds

I was asked to walk through why the work published earlier in the year by the Lund group is so important. I’ve put together a thread to walk through some of my thoughts.

https://twitter.com/DrInfoSec/status/1872658552852238579

First, here’s a link to the study.
nature.com/articles/s4159…

Let’s start with some context. Airborne viral transmission is exceedingly complex, but can be broken down into 3 general processes: production, transport and exposure. To estimate transmission and to design effective mitigation strategies, you must understand these processes.

Each of these broader processes contain within them various factors. In short, these processes explore how much infectious virus is exhaled, what happens to the infectious virus once it’s in the air, and how much is required to cause an infection (and where).

While my research is focused on what happens to the virus when it’s in the air, I would argue that the most important factor to understand is HOW MUCH infectious virus is actually exhaled. Everything else is downstream of this absolute quantity.

For example, if in a single exhalation a person exhaled 1,000,000,000,000,000 infectious virions, then this would have a massive effect on everything else. For example, it would mean that masks would have to be >99.999999% effective to work since the initial viral load is so high

Anti-maskers use this type of argument (plus they don’t seem to know that vapour is not aerosol…). Again, how you feel about risk and mitigation strategies is largely informed on what you think is the initial exhaled dose.

It also has a massive effect on how we figure out the infectious dose. There have been human exposure studies where subjects are intranasally inoculated with the virus in part to estimate the infectious dose. This isn't how people are exposed in the world.
nature.com/articles/s4158…

Aerosol deposition in a different part of the lungs may require far less virus. Meaning, to figure out the infectious dose, we need some way of quantifying the initial exhaled dose, and estimate the exposure from there.

There have been many studies measuring the numbers of aerosol that are exhaled by people during different activities such as breathing, exercising and singing. What is unknown is how these absolute numbers of aerosol particles equates to infectious virions
tandfonline.com/doi/full/10.10…

There have been numerous studies that report viral RNA (as measured by PCR). There are many reasons for this. 1st, the detection limit for RNA is very low. 2nd, RNA breaks down slowly relative to infectious virus
academic.oup.com/cid/article/76…

3rd, the air can be sampled for longer time periods without concerns for loss of signal due to the virus RNA breaking down in the sampler itself. In short, it’s easier to measure airborne RNA than actual infectious virus.

There are problems with solely measuring RNA and not the infectious virus. Here’s just a few concerns I have:
1) RNA isn’t infectious virus, therefore you can’t use it directly to estimate risk.

2) RNA breaks down very slowly when compared to infectivity. Thus, measuring RNA in a given sample doesn’t necessarily equate to risk.
3) The initial ratio between RNA and infectious virus is unknown. It is estimated to be 1:1000, but that can vary in time, disease state, etc.

4) RNA last longer everywhere. Meaning, the ratio of infectious virus to RNA will change in the respiratory fluids as well.

Essentially, measuring RNA to estimate transmission risk is like using the size of a graveyard to estimate the population of London. They are related, but there’s a lot more involved. And if you focus on studies that solely measure RNA you may end up missing a lot of the picture

Thus, to fully understand transmission, it is critical to know how much infectious virus is exhaled in a single breath (not just RNA). The assumption has been that the aerosol mass is proportional to the amount of infectious virus.

Essentially, one ought to be able to estimate the airborne viral load from just the concentration of the virus in the respiratory fluid and the mass of aerosol exhaled:

But is this true? To know, it needs to be measured. This is what the Lund team have done. And what they found was interesting. For example, the amoutn of RNA did not track with the amount of infectious virus.

They also found that the initial exhaled viral load is higher than what would be expected based solely on the aerosol size. The team then used this new information to model the risk of transmission. They found that transmission can occur quickly in poorly ventilated spaces.

I can not stress enough how difficult this study would be to set up. The team is not infecting people. Rather, they have a mobile unit they have built that will go to people that either first test positive, or begin to show some symptoms of infection. Logistically, this is HARD!

Anyway, those are some thoughts of mine on this very impressive and important study. I was bummed out to see shade being thrown at the authors earlier this week. Let's all try to do better in the New Year.