Thread by @SGriffin_Lab

Lots of good debate about virus transmission, yet it's dwarfed by mis/disinformation and lack of nuance, allowing eejits to dismiss the precautionary principle, or, worse, re-run 1980s bigotted attitudes🤬
Viruses don't fit easily into boxes. So, nuances of transmission, a 🧵

I will focus on the example of airborne transmission, but the underlying principles apply to all modes of infection.

Caveat: I research the start/end of the transmission process, but the middle bit is not my forte, so forgive omissions/errors!🙏
See @ukhadds for added nuance!

Right, so I would define transmission as the transfer of sufficient infectious virus from a site of infection or environmental source to an individual, followed by the successful establishment of a productive infection (ie the completion of the life cycle) within the new host.

There are some key concepts to understand before we get going:

1. Most virus particles are imperfect, unable to establish an infection regardless of whether they make the journey.
The ratio of non-infectious to infectious progeny is termed the particle: infectivity ratio.

2. Viruses r obligate intracellular parasites. They can't thrive without a permissive host.
3. Infection and pathology is a dynamic of virus, host, & environment.
4. Viruses are ultimately selfish genes. Their evolutionary drive is to multiply and spread. Disease is a byproduct.

5. B4 someone mentions Koch's postulates, or "isolation in purest forms" - former, out of date, latter shows abject lack of virology understanding.
6. Particles carry viral genomes. They r complex but all essentially comprise a protein shell. Some also have a membrane "envelope".

7. Dogma holds that non-enveloped virus particles, aka virions, are more robust in the environment. This is often true, but there are exceptions, e.g. hepatitis B virus.

8. The largest human virus particles, pox viruses, are still small enough (~300nm) to be carried by aerosols.

So, we can think of transmission in a series of stages, all of which are like an obstacle course for the virus.
The fact that something with a genome 6 orders of magnitude smaller than ours navigates these barriers, infects us, and moves on, has always astonished me, frankly...

Stage 1. Making enough virions at the right time, and in the right place.
Viruses hijack cells and turn them into factories, making more viral genomes and packaging them into virions, ready to be shipped out.
The tissues in which this occurs, therefore, dictates exit routes...

For example, blood borne viruses like HIV, HCV, HBV, etc, transmit via body fluids, so you see high viraemia, esp early infection.
Some cause high viraemia yet transmit via other routes, eg poliovirus.
Others, eg SARS2, have low viraemia, but high VL in resp tract, gut etc.

So, sometimes you find virus everywhere yet only one transmission route is favoured, sometimes it's obvious, but they are always adept at delivering progeny to the right tissues in a new host that favours the virus in terms establishing itself and spreading before it is stopped.

Any infection is a race, pitting rate and magnitude of virus replication, and so virion production, vs innate and adaptive immune systems; if latter is winning the race➡️ lower virus replication➡️fewer infectious particles made➡️lower virus load. But, virions are also targets.

Many stages by which new virions are formed and then shipped out of cells are targeted by innate immunity, mainly through interferon-driven responses.

Infected cells/factories are also targets for immune-mediated killing, whether innate (NK cells, ADCC) or adaptive (Tcells).

Even if sufficient virions are released, they must navigate multiple innate barriers (eg mucins, complement, lectins) and specific antibodies, all aimed at limiting spread and/or rendering particles non-infectious.
Genetics dictates our responses, bell-shaped curve time again...

Why is this important?
Two things. First, the ideal scenario is to mount a combined innate/adaptive response, and for the latter to be the more rapid/pronounced "memory response".

Hence, #Vaccines are critical for limiting onward spread as well as protection vs infection.

Second thing, it's hard to predict how infectious someone may or may not be, when this might happen, and it's not always coincident with symptoms or clinical signs of infection.
Yes, we have population averages for many viruses, but they are exactly that, an average...

So, the middle part...travelling through the environment.

Virions are complex, as I mentioned. They have a difficult job: to protect the genome from the environment whilst also being able to deliver it into a new host cell. Moreover, it needs to be the right part of the cell.

Hence, virions are "metastable". I.e. there are certain triggers that will literally cause them to fall apart...if they encounter these triggers at the wrong time, their journey ends.
Triggers can include pH, enzymatic cleavage, ionic strength, binding their receptor, etc.

Also, as with all biological entities, virions have varying degrees of sensitivity to temperature, dehydration, pH, ionic strength, etc.
Envelopes are often the most fragile components, but not always. Regardless, their properties are, by definition, evolutionarily advantageous.

So, I'll focus now on respiratory transmission as a) it's highly relevant to current public health threats, and b) it seems to have become a somewhat controversial issue.
The most extreme challenge of this route is airborne transmission via aerosols, i.e. v small fluid particles.

Aerosols are generated by different forms of exhalation and in different parts of the lung, but can also form via evaporation of larger droplets depending on the environmental conditions.
Droplets are a relatively comfortable environment for viruses, but aerosols are volatile.

For one thing, there's obviously a limit to the number of particles that can fit within an aerosol, but also issues wrt dehydration, salt concentrations (incl crystallisation) and pH, temperature, uv exposure, etc. They also disperse rapidly in ventilated spaces...hint, hint!

So, aerosolised viruses need to be able to survive these conditions w/o damage or any of their triggers being sprung. They also need to be both competent, and highly efficient at initiating infection...a bit like super swimmer sperms both reaching and fertilising the ovum first.

So, whether a virus is aerosolised AND infection via that route depends on 1) whether sufficient virus was made in the right bit of the lung, 2) surviving droplet evaporation, 3) having virions robust enough and infectious enough to establish infection at very low doses...

So, on to part 3, establishing infection...
This is not as simple as just mixing virus with the right cells, although this IS critical, naturally. For example, variola was highly pathogenic when infecting the lungs, yet far less so when the skin was infected, aka "variolation".

Link here to part 2...
Apologies for the waffle!

https://x.com/SGriffin_Lab/status/1826374821376381408?t=DE3t9s8bWDxN8Jgro25HlA&s=19