Well, they still have to outcompete the rest and evade whatever adaptation magic T-cells do, so I’m not too worried. Yet.
One thing to note: Flu vaccines don’t give you T-cells or memory B cells. The ones that exist right now only give you an antibody response, then it’s gone.
Note: paper was written in 2019. It would be a shame if something happened like a new “spanish flu”.
Persistent and durable immunological memory forms the basis of any successful vaccination protocol. Generation of pre-existing memory B cell and T cell pools is thus the key for maintaining protective immunity to seasonal, pandemic and avian influenza viruses. Long-lived antibody secreting cells (ASCs) are responsible for maintaining antibody levels in peripheral blood. Generated with CD4+ T help after naïve B cell precursors encounter their cognate antigen, the linked processes of differentiation (including Ig class switching) and proliferation also give rise to memory B cells, which then can change rapidly to ASC status after subsequent influenza encounters. Given that influenza viruses evolve rapidly as a consequence of antibody-driven mutational change (antigenic drift), the current influenza vaccines need to be reformulated frequently and annual vaccination is recommended. Without that process of regular renewal, they provide little protection against “drifted” (particularly H3N2) variants and are mainly ineffective when a novel pandemic (2009 A/H1N1 “swine” flu) strain suddenly emerges. Such limitation of antibody-mediated protection might be circumvented, at least in part, by adding a novel vaccine component that promotes cross-reactive CD8+ T cells specific for conserved viral peptides, presented by widely distributed HLA types. Such “memory” cytotoxic T lymphocytes (CTLs) can rapidly be recalled to CTL effector status. Here, we review how B cells and follicular T cells are elicited following influenza vaccination and how they survive into a long-term memory. We describe how CD8+ CTL memory is established following influenza virus infection, and how a robust CTL recall response can lead to more rapid virus elimination by destroying virus-infected cells, and recovery. Exploiting long-term, cross-reactive CTL against the continuously evolving and unpredictable influenza viruses provides a possible mechanism for preventing a disastrous pandemic comparable to the 1918-1919 H1N1 “Spanish flu,” which killed more than 50 million people worldwide.
Most of the existing products utilize inactivated virus, or isolated viral HA and NA proteins, that stimulate influenza strain-specific antibody immunity and B cell memory, but do not prime the much more cross-reactive CD8+ CTL compartment. The challenge is thus to add a T cell-targeted vaccine component that promotes CTL memory for the rapid recall of anti-viral CTL effectors to the respiratory tract for early virus control and/or induce cross-protective B cells.
[why the fuck are my edits not saving?]
For some reason, my edit isn’t saving for the last post.
A simpler paragraph to read:
Most of the existing products utilize inactivated virus, or isolated viral HA and NA proteins, that stimulate influenza strain-specific antibody immunity and B cell memory, but do not prime the much more cross-reactive CD8+ CTL compartment. The challenge is thus to add a T cell-targeted vaccine component that promotes CTL memory for the rapid recall of anti-viral CTL effectors to the respiratory tract for early virus control and/or induce cross-protective B cells.
You should know that the current mRNA vaccines are pretty good at this (and I’ve heard J&J and AZ do a decent job as well)
vinraith
1812
That would change if (hopefully when) we move to MRNA flu vaccines, right? That is, in the same way that they induce T-cell and memory B cell response for Covid they could do so for targetted flu strains?
A “shame” rather understates it! I’m reading a book on the Spanish Flu right now, and every about it seems so much worse than covid (except perhaps the transmissibility of Delta).
ShivaX
1815
If we didn’t have the technology we do Covid would be soooo much worse.
Take everyone that gets hospitalized and assume 80-90% of them die.
Yes, but’s that’s so for every pandemic. The Black Death, by far one of the worst we know of, we could just shrug away nowadays.
Pandemics impact need to be evaluated in context. This is nothing like the Spanish flu so far and it’s likely it will remain less impactful.
ShivaX
1817
Sure, but I was more commenting on the idea that the Spanish Flu was so much worse.
It was, but also a lot of that is technology. Imagine an antibiotic immune Black Death.
Horrifying and lethal, but still not as bad as it would’ve been in 1349.
Edit:
Madagascar had a resistant plague outbreak in the 90’s apparently.
Fatality rate was 11%
Fatality rate of Black Death: 80%
What’s the current fraction?
The Spanish Flu was killing 5% of healthy young adults in naval bases. We have flu specific treatments now, but I really don’t want to have to find out if they would work on a modern day influenza pandemic.
The other thing to remember in comparisons is that the demographics are wildly different. Average age was probably about 25 compared to close to 40 today. The West is a very grey demographic compared to the 1900s.
From what I’ve read, a good portion of the deaths were due to things like opportunistic pneumonia infections which would have been treatable if they had antibiotics then.
Then we have all the high intensity ICU supportive care which wasn’t available then, which allows at least some portion of patients to stay alive long enough for their immune system to win the fight.
We would also expect a Spanish Flu level epidemic to be enough of a spur to the development of monoclonal antibody therapies similar to the COVID ones.
And finally we have the modern anti-viral drugs, none of which seem awesomely effective, but you would expect to see them knock the fatality rate down by some percentage.
I think there are good reasons to be confident that Spanish Flu would be less bad now than it was then, without saying that it wouldn’t be dangerous at all.
Banzai
1820
a lot of rheumatological illnesses, even things like type 1 diabetes and hyper/hypothyroidism can happen due to these immune system mixups. they have been known for a long time. ive always assumed that this type of mixup was likely to be part of why young people sometimes have such a bad covid case.
its why steroids are useful in hospitalized covid patients but not helpful at the start of the illness when the inflammation is directed at the invading virus and helps to fight it. after the illness has mostly been wiped out, the steroids help to calm down the subsequent autoimmune response.
i tell patients that inflammation is like collateral damage during a war. sometimes the buildings take a pounding in order to take out the enemy. simplified, but mostly right and easy to understand.
Strollen
1821
The Gate’s foundation “Goalkeepers reports” is chock full of data on everything from childhood mortality to sanitation but this years had a lot of information about vaccines and PPEs.
vinraith
1822
@triggercut highlighted this on Twitter and I think it’s a very interesting read:
It’s also pretty broadly encouraging, though I still wish there was some movement toward more clearly defining long COVID. I mean, as suggested in the thread, I have most of the symptoms being described and I’ve never had COVID:
One much more clearly COVID-related symptom would be anosmia, and I haven’t seen much discussion of that one lately. Has anyone seen any data on temporary/permanent loss of smell? That would be a huge quality of life hit, it seems to me.
Yeah, there needs to be some way to classify long covid clinically and an agreed-upon set of symptoms or states of being that earn that distinction.
On “brain fog”:
TL;DR: Yes, it appears to be a thing.
I wonder if you can read type of care (hospitalized, ER, outpatient) as an indicator of severity of Covid? On the one hand, seems obvious. On the other, I don’t even play a doctor on TV.
Mmmm. Maybe.
But I have so many questions still. I am not a doctor or a medical researcher. But I do help design experiments and studies, and part of that is bringing up variables, confounders, and potential flaws to account for. So.
First: I’d like to see a study of people hospitalized for non-Covid reasons for similar lengths of time and how they performed on those cognitive tests post-care. Because we know that stress and trauma can impact brain reaction times and fast-processing. Perhaps Covid creates unique factors that impact cognitive ability that won’t be seen among non-Covid patients. But perhaps the trauma of the idea of having Covid creates a level of psychological impact, and being hospitalized creates a greater level? I don’t know. We don’t know. And in the short term, psychological causes and biological causes that lead to the same outcome are still leading to the same outcome. But that’s two different routes to help people avoid or mitigate those outcomes, too.
The other control I’d have maybe liked to have seen is a set of cognitive tests for a sample from April 2020 and then again in April 2021. Those were 12 tough months, with a lot of isolation and limited human contact. How does THAT impact cognitive agility? Maybe it doesn’t. But again, we know that trauma can be a potential impact here, so it’d be interesting to see if as a population we’ve all got a little bit more clumsy (so to speak) in cognitive function too.
(And to the credit of the doctors submitting that study, they clearly delineate that selection bias and sample bias are potential weaknesses in their work.)
jpinard
1827
That is one of my biggest worries from having covid.
Don’t worry; we’ll test you on what’s the best flavor of Pop Tart to verify you haven’t lost a step.
More seriously, that was my fear with my father; he was in and out of the hospital with COVID for a couple weeks last year. Honestly, it’s difficult to tell whether it’s fatigue or any kind of decline, but he didn’t seem quite as sharp after, and for a good while. Mostly back to normal, now, but this is over a year later.
