To Vaccinate or Not---The Rat Flu Odyssey Continues

[alpinevibes]

^^ And she's the supporting individual for a private school for kids? Wow, makes you wonder what their curriculum consists of. 'The Earth is flat!'

Reading her bio, you wouldn't expect such ignorance:

For many years Leila Centner was the Chief Financial Officer of Highway Toll Administration (HTA) until it was sold in March 2018. Prior to her work with HTA, Leila held several high-level financial roles with Arthur Andersen and Deloitte & Touche, overseeing engagements with multi-billion dollar accounting clients. Leila’s greatest joy comes from being part of humanitarian organizations such as Convoy of Hope and the Centner Foundation, which she co-manages with her husband David. A proud mother of two daughters, Leila graduated Magna Cum Laude from the University of Southern California’s School of Accounting and received her MBA from the University of California.

But there's this:

Ms. Centner founded the school with her husband, David Centner, a technology and electronic highway tolling entrepreneur. Each has donated heavily to the Republican Party and the Trump re-election campaign, while giving much smaller sums to local Democrats.

In February, the Centners welcomed a special guest to speak to students: Robert F. Kennedy Jr., the prominent antivaccine activist. (Mr. Kennedy was suspended from Instagram a few days later for promoting Covid-19 vaccine misinformation.) This month, the school hosted a Zoom talk with Dr. Lawrence Palevsky, a New York pediatrician frequently cited by anti-vaccination activists.

[funkendrenchman]

^ The theory has been studied: Previously-infected individuals tend to have a strong reaction to the first vaccine dose whereas the non-infected have a strong reaction to the second dose.

And what does it tell us about the group that has no reaction to either dose?

[The AD]

But there's this:

Yeah, seems like anyone associated with that school knew what they were getting into.

[Bobby Stainless]

got the 2nd modern yesterday about 5 PM. feel like shit today. YMMV

Got my 2nd Pfizer yesterday and feel like I was in a car accident. Day drinking is helping.

[wooley12]

Feeling sorry for you youngsters. My wife and I only had the normal mildly sore shoulder that was gone after 48 hrs and none of the boomers I speak to who got Pfizer mentioned any severe after shot affects. The Moderna kicked one retired couple pretty hard.

[Adolf Allerbush]

Mt Bohemia is having a contest. Get vaccinated...enter to win a lifetime seasons pass. Winning.

https://www.instagram.com/p/COJRdgSF...d=wbh0kj8289xg

And...Lonnie pokes the antivaxxers in the eyes. Lolz.

Sent from my SM-G981U using Tapatalk

most of the comments on there are depressing...lots of antivaxxers go to Mt Bohemia I guess. Maybe that shouldn't be surprising with the spike in cases in MI.

[uglymoney]

Of course they are triggered by this. Hilarious. Lonnie is kind of a crazy guy himself. He pulls shit like this because he doesn't give a fuck.

[old_newguy]

Any updated thoughts on protection while flying? I know last time this was discussed it was N95 and eye protection.

CDC seems to be indicating here that their guidance is explicitly recognizing that relaxing standards will encourage more people to get vaccinated and there is still uncertainty regarding the efficacy against some of the variants.

https://www.cdc.gov/coronavirus/2019...ed-people.html

I will be flying in about a month. I’m getting my last shot of Pfizer this week so will be ~4 weeks post vaccination.

[Mofro261]

COVID-19 vaccines: modes of immune activation and future challenges
Nature Reviews Immunology volume 21, pages195–197(2021) John R. Teijaro & Donna L. Farber

https://www.nature.com/articles/s41577-021-00526-x

The new vaccines against SARS-CoV-2 are novel in terms of specificity, their wide dissemination across the global population and the inclusion of newly licensed mRNA platforms. We discuss here how the approved vaccines trigger innate immunity to promote durable immunological memory and consider the future implications of protecting populations with these vaccines.

The global SARS-CoV-2 pandemic has caused significant loss of life, profound disruption to lives and livelihoods, and widespread economic, sociological and psychological damage. Severe COVID-19 involving acute respiratory distress syndrome (ARDS), multi-organ failure and death remains the most serious threat from infection, but long-term sequelae from mild disease have also been reported. The high transmissibility, presence of asymptomatic carriers and emergence of new variants have had a prolonged effect on the global population for the past year and counting. Vaccination constitutes the most promising path back to ‘normal life’; here, we discuss how the newly approved vaccines can mobilize innate and adaptive immune responses, implications for their durability, and ongoing and future challenges for protecting the population.

Approved vaccine formulations
Significant advances in cutting edge vaccine technologies over the past decade have resulted in two main types of SARS-CoV-2 vaccines now being approved for emergency use — an unprecedented achievement in modern medical science. The approved vaccines developed by Pfizer and Moderna use mRNA technology and lipid nanoparticle (LNP) delivery systems, while the approved formulations by AstraZeneca, Johnson and Johnson and Gam-COVID-vac (Sputnik V) contain DNA delivered within non-replicating recombinant adenovirus (AdV) vector systems1,2,3,4. Both the mRNA and AdV vaccines encode production of the SARS-CoV-2 spike (S) protein, which is the primary target for neutralizing antibodies generated from natural infection and for therapeutic monoclonal antibodies1. To date, results from the phase III clinical trials showed that both the Pfizer/BioNTech (BNT162b2) and Moderna (mRNA-1273) mRNA vaccines achieved 90–95% efficacy in protecting against COVID-19 (refs1,2), while the AdV vaccines (ChAdOx1 nCoV-19) and Gam-COVID-vac (Sputnik V) showed protection at a slightly lower efficacy (average 70% and 91%, respectively)3,4. Both vaccine types generate significant neutralizing antibody titres and virus-specific T cell responses as measured in blood 2–4 weeks post inoculation5,6. These trials, which collectively involved more than 100,000 participants, provide compelling rationale for expedient and widespread vaccination of the global population. While the AdV vaccine platform has been licensed for Ebola, the mRNA vaccine platform represents a newly licensed formulation. Thus, we still have much to learn about how these vaccines mobilize the immune response, the durability of protection and how to further optimize them to protect against new variants, strains and disease manifestations.

Triggering innate and adaptive responses
To stimulate adaptive immunity, a vaccine requires a pathogen-specific immunogen as well as an adjuvant — the latter stimulates the innate immune system and provides the necessary second signal for T cell activation. An optimal adjuvant stimulates innate immunity without inducing systemic inflammation that could elicit severe side effects. For mRNA vaccines, the mRNA can serve as both immunogen (encoding the viral protein) and adjuvant, owing to intrinsic immunostimulatory properties of RNA. Upon entry into cells, single-stranded RNA (ssRNA) and double-stranded RNA (dsRNA) are recognized by various endosomal and cytosolic innate sensors that form a critical part of the innate immune response to viruses. Endosomal Toll-like receptors (TLR3 and TLR7) bind to ssRNA in the endosome, while components of the inflammasome such as MDA5, RIG-I, NOD2 and PKR bind to ssRNA and dsRNA in the cytosol, resulting in cellular activation, and production of type I interferon and multiple inflammatory mediators7 (Fig. 1). The current vaccines contain purified, in vitro-transcribed single-stranded mRNA with modified nucleotides to reduce binding to TLR and immune sensors, thus limiting excessive production of type I interferon and its inhibitory function on cellular translation (see ref.7). The LNP carrier further protects the mRNA, can target delivery to lymphatics and promote protein translation in lymph nodes (LNs)7. Once in the LN, the LNP is engulfed by dendritic cells (DCs), which subsequently produce and present the antigen to T cells for activation of the adaptive immune response.

The AdV vaccines also contain inherent adjuvant properties, although these reside with the virus particle that encases the DNA encoding the immunogen. Following injection, AdV particles target innate immune cells like DCs and macrophages and stimulate innate immune responses by engaging multiple pattern-recognition receptors including those that bind dsDNA — in particular TLR9 — to induce type I interferon secretion8. Unlike AdV vectors, mRNA vaccines do not engage TLR9, but both vaccine formulations converge on the production of type I interferon (Fig. 1). Type I interferon-producing DCs and other cells that have taken up the vaccine-derived nucleic acids encoding the S protein can deliver both an antigenic and inflammatory signal to T cells in LNs draining the injection site. This activates S protein-specific T cells and mobilizes adaptive immunity against SARS-CoV-2 (Fig. 1).

The ability of mRNA and AdV vaccines to promote intracellular production of S protein along with innate immune responses should prime both CD8+ and CD4+ T cells to differentiate into effector and memory subsets. In particular, vaccine-driven production of type I interferon promotes differentiation of CD4+ and CD8+ effector T cells producing inflammatory and cytotoxic mediators, and CD4+ T follicular helper (TFH) cells, which promote B cell differentiation into antibody-secreting plasma cells (Fig. 1). Both the mRNA and AdV vaccines require two doses spaced 3–4 weeks apart to promote optimal protection and have been associated with mild to moderate side effects, including injection site pain, transient fever and chills, which can be augmented with the second dose. This secondary enhancement of the inflammatory response can derive from short-term changes to innate cells like macrophages through a phenomenon called ‘trained immunity’9, and/or from activation of memory T cells and B cells generated from the initial injection. Type I interferon has been shown to amplify T cell memory and promote B cell differentiation and survival, suggesting vaccine-associated inflammation in the booster can further promote generation and perpetuation of long-term immunological memory.


The two vaccine formulations — mRNA encoding the SARS-CoV-2 spike (S) protein encapsulated in lipid nanoparticles or adenovirus (AdV) vectors encoding the S protein — gain entry into dendritic cells (DCs) at the injection site or within lymph nodes, resulting in production of high levels of S protein. In addition, innate sensors are triggered by the intrinsic adjuvant activity of the vaccines, resulting in production of type I interferon and multiple pro-inflammatory cytokines and chemokines. RNA sensors such as Toll-like receptor 7 (TLR7) and MDA5 are triggered by the mRNA vaccines, and TLR9 is the major double-stranded DNA sensor for the AdV vaccine. The resultant activated DCs present antigen and co-stimulatory molecules to S protein-specific naive T cells, which become activated and differentiated into effector cells to form cytotoxic T lymphocytes or helper T cells. T follicular helper (TFH) cells help S protein-specific B cells to differentiate into antibody-secreting plasma cells and promote the production of high affinity anti-S protein antibodies. Following vaccination, S protein-specific memory T cells and B cells develop and circulate along with high affinity SARS-CoV-2 antibodies, which together help prevent subsequent infection with SARS-CoV-2. TCR, T cell receptor.

[Mofro261]

con't


Durability and future challenges
Preclinical and early results from human trials show that both vaccines generate anti-S protein IgG and virus-specific neutralizing antibody responses for several months post-vaccination5,6, while the T cell data remain to be fully elucidated. This short-term durability is likely sufficient for curtailing the spread of SARS-CoV-2 and beginning the path back to normalcy. However, the global pervasiveness of SARS-CoV-2 along with the emergence of S protein variants could potentially limit vaccine efficacy. Eradication of SARS-CoV-2 from the population may prove challenging, owing to reservoirs within individuals who are not vaccinated and/or in other animal species. New vaccine formulations containing the variant S sequences and additional SARS-CoV-2 proteins could be generated, and annual or semi-annual SARS-CoV-2 vaccines could be given for persisting strains and/or seasonal variants. The mRNA vaccine formulation is ideally suited for repeat or modified vaccination as different mRNAs containing mutant S proteins can be rapidly synthesized and included within the LNP carrier. By contrast, the AdV vector formulation generates AdV-specific immunity, which can limit efficacy of repeated boosters owing to immune-mediated clearance of the vector.

The unprecedented mass and simultaneous vaccination of the global population will undoubtedly reveal heterogeneity in vaccination responses and some individuals may not generate robust antibody responses or be protected. Immunity to respiratory viruses can be mediated by tissue-resident memory T (TRM) cells that are established in the lung during the initial infection and retained as non-circulating populations that mediate protective responses in situ upon viral re-challenge10. TRM cells can be generated from site-specific vaccination with attenuated viral vaccine formulations10. It would be interesting to determine whether intranasal delivery of mRNA vaccines can promote TRM cells and protection in the lung. The development of self-replicating mRNA vaccines (which mimic viral replication) may also enhance protective T cell immunity. Such alterations in formulation and delivery route could be used to optimize the vaccines according to immune status and age.

In conclusion, the SARS-CoV-2 pandemic has accelerated the licensing of promising vaccine formulations that provide hope for fortifying our immune systems against the current and future emerging pandemics.

[The AD]

Of course they are triggered by this. Hilarious. Lonnie is kind of a crazy guy himself. He pulls shit like this because he doesn't give a fuck.

The Keewenaw Peninsula has got to be a pretty crazy demographic with the mix of educated folks at Tech, the Finns, and your basic UP rednecks.

[old goat]

No doubt you know more about this than I do, or a pharmacist for that matter. I did ask her if she meant anti-inflammatory (i.e., advil, etc.) drugs or any over the counter pain killer and she said the latter, inclusive of tylenol (acetaminophen)...her explanation was that anything that keeps your body from allowing it to have whatever viral response (i.e., aches, fever, etc.) it would otherwise have to the vaccine is reducing the effectiveness of the vaccine. Is that true? hell if I know, but it made sense at the time. Her recommendation was to suck it up and deal with the symptoms unless you absolutely cannot stand it.

According to the CDC we're both wrong.
https://www.cdc.gov/coronavirus/2019...ect/after.html
"Talk to your doctor about taking over-the-counter medicine, such as ibuprofen, acetaminophen, aspirin, or antihistamines, for any pain and discomfort you may experience after getting vaccinated. You can take these medications to relieve post-vaccination side effects if you have no other medical reasons that prevent you from taking these medications normally.

It is not recommended you take these medicines before vaccination for the purpose of trying to prevent side effects."

(Same thing KQ posted but straight from the horse's mouth).
What evidence there is to support the CDC's recommendation I don't know.

As far as pharmacists and doctors--I'd say in general pharmacists know more about a wide range of drugs than doctors.

[skaredshtles]

most of the comments on there are depressing...lots of really dumb fucks live in Michigan.

Fixed that for you.

[KQ]

According to the CDC we're both wrong.
https://www.cdc.gov/coronavirus/2019...ect/after.html
"Talk to your doctor about taking over-the-counter medicine, such as ibuprofen, acetaminophen, aspirin, or antihistamines, for any pain and discomfort you may experience after getting vaccinated. You can take these medications to relieve post-vaccination side effects if you have no other medical reasons that prevent you from taking these medications normally.

It is not recommended you take these medicines before vaccination for the purpose of trying to prevent side effects."

(Same thing KQ posted but straight from the horse's mouth).
What evidence there is to support the CDC's recommendation I don't know.

As far as pharmacists and doctors--I'd say in general pharmacists know more about a wide range of drugs than doctors.

I took one advil dual action (Acetaminophen 250mg and Ibuprofen 125mg) 12hrs after my 2nd jab because my back was killing me. It was unrelated to the jab, woke up with it from sleeping like a pretzel (damn cats!) and knew it was going to present a problem for me getting a good night's sleep which I felt was more important for my health than tossing and turning in agony all night long.

Maybe I negated my jab, maybe not. Will just have to see how it goes.

[Gcooker]

I'm 6 days out from the AZ shot, initial arm soreness and headache subsided so I figured I was all good. Super sore arm pits yesterday afternoon and night, but fine today. Swollen lymph nodes was unpleasant.

[MontuckyFried]

According to the CDC we're both wrong.
https://www.cdc.gov/coronavirus/2019...ect/after.html
"Talk to your doctor about taking over-the-counter medicine, such as ibuprofen, acetaminophen, aspirin, or antihistamines, for any pain and discomfort you may experience after getting vaccinated. You can take these medications to relieve post-vaccination side effects if you have no other medical reasons that prevent you from taking these medications normally.

It is not recommended you take these medicines before vaccination for the purpose of trying to prevent side effects."

(Same thing KQ posted but straight from the horse's mouth).
What evidence there is to support the CDC's recommendation I don't know.

As far as pharmacists and doctors--I'd say in general pharmacists know more about a wide range of drugs than doctors.

This is actually a REALLY interesting topic that deserves more discussion. Earlier I just parroted what a doctor had told us in the past which made sense in relation to what Adolf was saying. However, after doing a bit more looking online, ends up there is a TOOOOOON of fascinating information about the relationship between high temperatures and immunity. It's far more involved than I can succintly regurgitate in a single post, so take a quick look at some of these studies if you care to:

Elevated body temperature helps certain types of immune cells to work better, evidence suggests:
https://www.sciencedaily.com/release...1101130200.htm

Why fever can be your friend in times of illness -Fevers are more than just a symptom of illness or infection, claim researchers; elevated body temperature sets in motion a series of mechanisms that regulate our immune system, they found:
https://www.medicalnewstoday.com/articles/321889

Fever and the thermal regulation of immunity: the immune system feels the heat
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786079/

And those are just a quick snippet of what you'll find. Gazillions of studies out there on it. My take away from all of this is basically that perhaps we should not try to fight the fever after getting the vaccine (or COVID itself). Unless it gets to dangerously high levels, maybe we need to suck it up and ride it out for the most effective immunity. You know a helluva lot more than I ever will when it comes to medicine, so can you tell me if I'm at least on the right track with my thinking here?

[Adolf Allerbush]

This is actually a REALLY interesting topic that deserves more discussion. Earlier I just parroted what a doctor had told us in the past which made sense in relation to what Adolf was saying. However, after doing a bit more looking online, ends up there is a TOOOOOON of fascinating information about the relationship between high temperatures and immunity. It's far more involved than I can succintly regurgitate in a single post, so take a quick look at some of these studies if you care to:

Elevated body temperature helps certain types of immune cells to work better, evidence suggests:
https://www.sciencedaily.com/release...1101130200.htm

Why fever can be your friend in times of illness -Fevers are more than just a symptom of illness or infection, claim researchers; elevated body temperature sets in motion a series of mechanisms that regulate our immune system, they found:
https://www.medicalnewstoday.com/articles/321889

Fever and the thermal regulation of immunity: the immune system feels the heat
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4786079/

And those are just a quick snippet of what you'll find. Gazillions of studies out there on it. My take away from all of this is basically that perhaps we should not try to fight the fever after getting the vaccine (or COVID itself). Unless it gets to dangerously high levels, maybe we need to suck it up and ride it out for the most effective immunity. You know a helluva lot more than I ever will when it comes to medicine, so can you tell me if I'm at least on the right track with my thinking here?

yeah, seems like the two main things are:
1. Don't preemptively take OTC pain meds prior to being vaccinated.
2. Try to avoid OTC pain meds unless your fever is dangerously high.

[XXX-er]

Fatigue?! Headache?! You're suggesting "I feel tired and I have a headache" are meaningful metrics for a study of vaccine side effects? If so, then my girlfriend had vaccine side effects the other night, 3 weeks after her shot no less. (cue rimshot) And even if they do count as vaccine side effects, they certainly wouldn't count as "severe side effects", which is the set of side effects I've been talking about the whole time.

And for the others, it's kinda hard to eyeball from their graph, but there's no way any of them are above 5%.

3 weeks later why would you assume side effects from Vax instead of she just got sick?

[smmokan]

Any updated thoughts on protection while flying? I know last time this was discussed it was N95 and eye protection.

CDC seems to be indicating here that their guidance is explicitly recognizing that relaxing standards will encourage more people to get vaccinated and there is still uncertainty regarding the efficacy against some of the variants.

https://www.cdc.gov/coronavirus/2019...ed-people.html

I will be flying in about a month. I’m getting my last shot of Pfizer this week so will be ~4 weeks post vaccination.

Wear a mask and don't sweat it. You'll be fine.

[MultiVerse]

Fatigue?! Headache?! You're suggesting "I feel tired and I have a headache" are meaningful metrics for a study of vaccine side effects?

I'm not suggesting anything because that's literally what the study says. One thing to keep in mind is the seronegative population is larger than the seropositive population. Even though seropositive individuals experience higher side effect frequency that doesn't necessarily mean more seropositive people are experiencing side effects. If otherwise cautious people are seeking out vaccination while previously infected are abstaining then simply saying all people experiencing side effects had a previous infection wouldn't make sense. Greater than 20% of a larger seronegative population is still a large number, it might even be a higher percentage of the vaccinated population.

[KQ]

just going to bitch about this here because I'm not going to get into it on FB with a bunch of anti-vaxxers:

Ugh... people are arguing against the jab on an OR health FB page because "why get vaccinated if you can still catch it?" well... same reason you wear a seatbelt - to mitigate the damage. Sure you can still die in a car accident wearing a seatbelt but the odds of survival are better.

[uglymoney]

For every point they have a phallic counter point that either makes no sense or is completely irrelevant. Discussing with a true anti vaxxer is pointless.

Biden said the other day we need to treat this like a get out the vote campaign. He couldn't be more on point. I deal with quite a few low information low wage workers and many say they will get vaccinated...but it is not at all a priority for them. They can't be bothered to schedule one quite yet. They don't have time to drive to one. If they are young they don't want to bother with the side effects really. It is all too much hassle for them.

Two examples from canceled appts from this week from people I contact at work. They had to change a friend's alternator. Another was nobody was around to watch the kids and the clinic wouldn't allow kids to come along.

I think we have so much fruit on the tree left to pick before we worry about the anti vaxxers. We need to identify and put the shots in front of these people asap. Like rolling vaccine buses going door to door or similar in your face strategies.

[Not DJSapp]

Biden said the other day we need to treat this like a get out the vote campaign. He couldn't be more on point. I deal with quite a few low information low wage workers and many say they will get vaccinated...but it is not at all a priority for them. They can't be bothered to schedule one quite yet. They don't have time to drive to one. If they are young they don't want to bother with the side effects really. It is all too much hassle for them.

I think we have so much fruit on the tree left to pick before we worry about the anti vaxxers. We need to identify and put the shots in front of these people asap. Like rolling vaccine buses going door to door or similar in your face strategies.

This is why the J+J vax is so good. You just need to corner these folks for 15 minutes and it's done. Store managers at the front of Costco, Walmart and CVS asking everyone who walks in if they have had their shot, and if not they can get poked and do their shopping during the 15 minute waiting period. Convert buses to mobile pop-up clinics and drive to businesses, malls, etc.

The Bay area is starting to open up for walk in appointments. This is the next phase. Get the people that aren't making it a priority in their lives.

[old_newguy]

This is why the J+J vax is so good. You just need to corner these folks for 15 minutes and it's done. Store managers at the front of Costco, Walmart and CVS asking everyone who walks in if they have had their shot, and if not they can get poked and do their shopping during the 15 minute waiting period. Convert buses to mobile pop-up clinics and drive to businesses, malls, etc.

The Bay area is starting to open up for walk in appointments. This is the next phase. Get the people that aren't making it a priority in their lives.

Always surprised me that my state wasn’t running mobile clinics in a sprinter van to all of the factories and grocery stores to vaccinate the workers.

Maybe that is the next step as you say.

[XXX-er]

putting the vax in tattoo ink is the way to get more people vaxed