UKC

Just musing after the news reports to day that prior exposure to the coronaviruses that cause the 'common cold' may impart some immunity to covid-19. This came out of a study on individuals in family situations who did not get covid, when everyone else in the household did.

That led me to thinking about the concept of viral load, and what happens in the body if it is exposed to a viral load below some threshold of infection. What happens to the viral contamination that does enter the body? Is it attacked and destroyed without triggering a full immune response (antibody generation and t-cell memory)? Or does the body learn from that sub-infectious viral load? If that is indeed 'a thing'.

If viral load is a contributing factor how come there are such varied responses to the vaccinations when the dose is tightly controlled? I think personal biology is a greater factor.

Personal biology may mean viral load is different for each person. But it also begs the question about whether 'personal biology' is also 'prior, sub-infectious exposure'; that's what I'm wondering about. And hoping the viral microbiologists on UKC will chime in to illuminate me...

No expertise to offer here so I'll generally stay out - but think vaccine response is irrelevant as you're not being exposed to 'virus'.

If only one virion gets in, which isn't typically enough to cause a full on infection, you are being exposed to virus - the body is getting rid of it - if it wasn't, there would be a viable infection, as per an immunosuppressed person.

This isn't my (admittedly poor) understanding of mrna vaccines (as opposed to live virus vaccines such as measles). But happy to stand corrected and don't want to derail the purpose of the thread.

NG's point is that the mRNA vaccines are not passivated virus; so the vaccine does not expose you (intentionally) to even a single covid virion.

Vaccine response isn't irrelevant. Vaccines present parts of the virus to train the immune system. This is the same way the immune system works naturally, only white blood cells smash up the full virus first so the breadth of pieces training the immune system is broader. Immune responses aren't on/off, but a massive spectrum dependant on many different elements. An individual's immune health is one of these, as is prior exposure to related viruses, as is viral load. Many systems kill viruses (including passive factors like stomach acid), plus there's a degree of luck in a virus binding its target site. Therefore, the more viral particles, the higher the infection risk. The same applies to learned immunity - a small viral load may not trigger any memory of the virus. 

Oh, I see, I thought they were referring to a low level infection fought off before it developed into a viable 10 days' worth, not a vaccine.

I've also wondered this. I was exposed (my husband had covid at Christmas, but the 'mild cold' type). I'd already had my booster and I kept taking PCRs / LFTs and never tested positive. But I had one day when I felt awful with omicron-like symptoms: headaches, sinus pains, fatigue. I was fully expecting to have a confirmed case that day but again my PCR was negative. Was this just my immune system fighting it off? Or just coincidentally another cold or virus? Obviously we were isolating so I hadn't been anywhere much.

There's another option, which might not be true in your case, but I'd imagine is a thing; not swabbing correctly for the test.

I've seen people make a right mess of testing.

Wondering just this, partner infected, I felt rubbish the day after he tested but 2x pcr and daily LFT always negative (and I know how to do the swab). Hoping I got a little bit of infection-acquired immunity along the way. 

Possibly but my son had a positive test which I swabbed so I can definitely do it correctly (plus I have a non-swabbing PCR test regularly through my work) so I generally don't think that's the case here.

Hmmm.  I guess the answer to the last bit is yes, your immune system quite often identifies and eliminates pathogens subclinically, especially if the infection comprises few pathogens or is concentrated locally.  You only really become aware of feeling poorly when infections become systemic, with the systemic release of cytokines like IL-1, IL-2 and TNF alpha.

For bacteria, the correlation of load and time to symptoms is easy to picture.  If you, for instance, eat something that contains a small inoculation of some potentially pathogenic bacterium (Salmonella, Campylobacter etc) then it's a race between the doubling time of the bugs and the speed with which they are passing though the gut.  It's complicated by the potency of any toxins they are releasing and, especially, whether they can attach to the wall of the gut (like the enteropathic E coli strains) and/or penetrate the gut wall and enter the blood stream (like, from memory, typhoid).  However, a big inoculum from, for example, a single bad mussel (to cite a vivid personal experience) can produce a very rapid onset of symptoms. 

For viruses, it's a bit more complicated.  A single virus, once it binds to and enters a suitable host cell, can replicate itself into hundreds of new viruses in one round of replication.  So, yes, having a greater initial dose is likely to lead to more serious symptomatic disease more quickly.  In the case of an individual who has encountered the virus before, there may be sterilising antibodies (sIgA) present on the surface of mucous membranes or IgM or IgG in the blood.  it seems logical that a massive dose of virus is more likely to escape or saturate the population of specific antibodies and then go on to successfully find its preferred receptor and infect a host cell.  It's a lot more complicated than that because of the presence of the innate neutrophil and macrophage response, NK cells and Tc cells, and the question of relatively inaccessible immune privileged sites.

For an airborne infections, it's also probable to being exposed to a high concentration of aerosol particles will result in more of them penetrating more deeply into the lungs, and so contacting not just the tracheal and bronchial epithelia (with their wonderfully named mucociliary escalator that traps such particles and transports them back up the respiratory tract for swallowing into the stomach) but the crucial alveolar cells.     

So, it's difficult to model exactly, but, in general, a smaller dose definitely helps to produce less serious disease, assuming it's accessible to the immune system, but small doses are normally adequate to provoke a (hopefully proportionate) immune response.

And I know there's a whole literature on how small doses of antigens can lead to tolerance and anergy in some circumstances.  As I say, it's complicated.   

Thanks. So... it's complicated...

I did consider that the immune response is layered, and that there may be some generic defence mechanisms that respond first, to low-level intrusion, but that don't trigger a memory. Is that true?

You really should watch that Storybots link...

youtube.com/watch?v=0ECPrtjnoCg&

The macrophages are very cute.

I did wonder if it might give me what I'm looking for; I found that link after I had posted this thread. I did start to watch it, but it seemed to not get to the point, or start telling me anything. I know you hate YouTube videos as a means of exchanging information, too... I'll go and see if I can endure it a bit longer...

I can’t abide talking heads videos, but this is a cartoon with songs!  Also after some of the other shows I’m subject too, this is quite refreshing.  Because it’s not Paw Patrol.

I don't want a cartoon with songs. If I did, I might have had kids...