Do scientists fully understand the variability in human response, to the second dose of Covid vaccine?

Pfizer and Moderna under discussion here.

Understood : The vaccine is effective no matter the bodily response. Also understand all the simplified examples like : “The first shot is like this … and second shot is like this …”

Science has been wrong in this Covid journey in initial stages : for example scientists misunderstood the spread through surfaces initially. If studies have not been conducted to look into the variability of human response, that’s okay - but I’d like an answer that’s scientifically validated rather than one from “first principles”

What exactly are you asking? Are you talking about variation in efficacy, or about other things like side effects? Why ask about the second dose specifically?

The efficacy figures that are the headline results of the trials obviously incorporate any variation in response to vaccination in the sample population. So the large trials (and a lot of subsequent data on efficacy) place a reliable upper bound on the size of the variation. Are you asking if there is research into factors that might explain any variation in response?

@Riemann sorry for the late response. I am interested in the answer to the following question :

Take a person A. Say all the data relevant to A is available to science : Age, Gender, Medical History, …

Can Science/Scientists reliably predict if person A will have a fever greater than 100F when given the second dose of Moderna / Pfizer vaccine ?

Side effects. And I have narrowed it down to fever, since it is the easiest to measure.

Anecdotally, the second dose causes the most variation in symptoms.

I don’t know the answer to your exact query, but I did find this article when I was looking up this for my own knowledge:

Despite the title, what is known seems to be fairly vague, like that it’s more likely to be worse for women, those under 55, those who have had COVID-19 before, and those whose immune systems tend to react strongly to things likes the common cold.

Nothing is specifically mentioned about fever. And I don’t know know what studies, if any, they are going by.

Doubtful. It’s quite unusual for something like a fever response to a vaccine to boil down to few enough factors to get that kind of knowledge out of a vaccine trial, or the (somewhat flawed) VAERS.

@BigT - thank you for looking into it.

So from the cite you posted, the article begins : “After millions of Americans have finally received the COVID-19 vaccine, doctors can finally detect trends of who is more likely or not to experience the vaccine side effects.”

“can finally detect trends” - means correlation data to me. But then the article title says, : " Doctors can predict …" So doctors are predicting based on some correlation data ? Where can someone see this correlation study ?

Scientists can’t reliably predict what type of reaction to COVID any individual person would have right now.

There are numerous factors, all highly variable. The immune system is (by evolutionary design) the most variable part of the genome. And the adaptive immune system develops in response to the pathogens you’re exposed to, so even two people with identical genotypes could have very different immune systems. Then other factors like age, sex, many aspects of medical history.

So it’s going to be a complex picture. We have a lot of data from vaccination programs, so we’ll get overall broad correlations like those alluded to in the article linked above. But those correlations aren’t powerful enough to be strongly predictive for any specific person. The extent of our knowledge will be risk factors that make side effects more or less likely.

For really serious side effects like the blood clotting issue people are going to devote some research effort to figuring out exactly what’s going on. But if it’s a question of whether or not you’re going to get a few of days of flu-like symptoms, we’re just unlikely to want to devote research resources to being able to predict that with certainty. Even if we did the research, accurate prediction for an inidividual would probably require things like testing immune response, genotyping the immune system - tests that are just not worth doing for such a purpose. Research effort is better spent just trying out various different vaccines to find out if we can develop versions where the overall incidence of unpleasant side effects is lower, not trying to predict exactly which people will get the side effects.

Thank you @naita and @Telemark

Thank you Riemann. I understand what you are saying. There’s a lot of bad information out there : I’ve had friends come to the conclusion that their immune systems must be really weak because they had a terrible fever after the second dose. Others think their immune system is strong, because they had no side effects.

I think it is important for Scientists to point out that the side effects are random and not a good predictor of a person’s immune health. Otherwise, many may skip the booster shot thinking their immune system is great and they need no booster shot.

Beyond that, I don’t think they’re even at the point of being able to predict that sort of thing for vaccines that have been around for decades.

I mean, I’ve had a LOT of flu shots over the years, and they all sort of hit differently. One will have no side effects, others will give me mild fever (99-ish) and body aches, and some will just make me feel less than spiffy, in a sort of vague, unfocused kind of way. And I got a tetanus shot once that made my entire deltoid on that side swell up and turn red for several weeks- my doctor had never seen anything like that before.

Plus unlike the mRNA COVID vaccines, some vaccines aren’t 90%+ effective. Some aren’t even 80% effective. And that’s not something that can be predicted either; if it was predictable, they could probably tweak the vaccine to make it more effective.

So I’m pretty convinced that the human immune response is only predictable in the broadest of strokes- i.e. if we give you this vaccine, you’ll probably be immune to the disease. But anything more specific than that is beyond our ken at the current time.

A fever is an immune response. To the extent they make sense at all your friends’ conclusions are exactly backwards. But the strength of side effects is, according to the trials, not correlated with having developed immunity.

There are two principal parts to the immune system, the innate (nonspecific) response and the adaptive (specific to a pathogen) response (aka acquired immunity). The innate system responds to things that generically indicate the likely presence of pathogens. As a restraint to stop your adaptive immune system overreacting constantly, some degree of innate response is required before the adaptive system will kick into gear and “learn” to recognize a specific pathogen (in this case the spike protein). For this reason, many traditional vaccines require what’s called an adjuvant, which is something that’s added to deliberately heighten the innate response.

It has been found that the mRNA vaccines don’t require an adjuvant, because the RNA itself serves this purpose. There’s plently of RNA in your body, but your immune system knows it should all be inside your cells, so if there’s RNA floating around your innate immune system is alerted.

Any side effects you see (at least from the first shot) will be the innate response, likely a response to the generic presence of RNA. And so far as I’m aware, the strength of side effects have not been shown to be strongly correlated (either positively or negatively) to the adaptive “learning” response that follows. You’d probably get a similar innate response even if (for example) the shot had inadvertently been left out of the freezer and the RNA were degraded and functionally useless. So I don’t think the side effects can even reliably tell you if you were given a “good” shot of vaccine.

Thank you for explaining it so well.