Sigh, time to update my dating profile… 
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UGA has a huge spike right now and I’ve heard that the food program they’ve implemented is piss poor, like fyre festival levels of bad, with huge long lines and people having to haul ass across campus (UGA’s campus is pretty large). I bet a good number of those kids who are from here are going to drive home this weekend for labor day and get a bunch of family members sick.
And of course, people have been going out to bars downtown right off campus, too, which is probably the largest vector for spread right now. A-town is fucked and so is the rest of GA.
It does seem like GSU and Emory are doing a better job at least. But I’ve not heard about Kennesaw (the other large university around the ATL), which is in a more red area than GSU and Emory.
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I think that is true, to varying degrees, with any university doing in-person lectures and labs. And totally predictable, which is maddening. But to bring the students in just long enough to get them exposed, then send them back to wherever they came from seems almost designed to spark increased cases and fatalities. I understand the motivation is mostly CYA and “we don’t have the resources to care for them here” (JMU has ~50 quarantine beds left as of yesterday) but you know that before you brought the kids back, and the outcome was known beforehand also. There is just no excuse for this shitshow.
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Indeed! But we live in neo-liberal land, and most public colleges and universities have been taken over by that mindset. The goal is no longer to educate the next generation, it’s to get as many people as possible crammed through your university, with as many graduating as possible, taking as much money out of their pockets as you can along the way. It’s becoming increasingly clear that the university in American life is yet another place where we’ve all been failed as a society.
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Two days before the election. What a coincidence.
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Well, that’s modern science for ya.
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The same company that’s up to its eyeballs in the opioid epidemic blowback. Great.
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Well at least people won’t be complaining about how rubbery the food is
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A few years back the kids and I spent a summer dissecting things - worms, crayfish, frogs. It was actually great fun. I understand not everybody’s cup of tea, but we had fun and got an education not offered in the local school system. (Rumor has it that the dissection classes were dropped due to potential discussions of evolution.) Yes, that is extreme privilege, I know, but a summer of memories!
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The immune system is hideously complex. You have
- The ‘innate’ immune system, which is not specific to any given pathogen. It basically cleans up foreign matter, destroys some foreign organisms, and mediates inflammation. The function of inflammation is largely to wall off damage and to start the other immune systems to mount a more specific response.
- The ‘adaptive’ immune system, that learns to recognize specific invaders by their chemical signatures.
The adaptive immune system in turn has several different responses:
- Cellular immunity. Specific cell types in the body are primed to recognize fragments of the organism.
- Humoral immunity. Circulating antibodies, produced by certain types of immune cells, can cause one of several responses.
- Neutralization: They can inactivate the invader directly by attaching to some aspect of surface chemistry that it needs to function
- Opsonization They can mark the invader as an enemy, promoting yet another type of immune cell to ingest and destroy it.
* Complement activation The marking of the invader as an enemy can promote the same pathways as the innate immune system to wall off the infected region and destroy the invading organisms.
So far I’m describing systemic immune response, but there are also immune responses - once again, mediated by specific cell types in specific organs. Rather than circulating in the blood, which is where we usually think immune cells live, about half the immune cells in the body live in the gut, bronchus, nose, conjunctiva of the eye, larynx, skin, and genital tract. The largest single concentrations of them are in the tonsils and adenoids.
Mucosal immune response is mediated by yet another family of immune cells and yet another family of antibodies. Like the systemic response, it has both innate and acquired components.
The RaDVaC project is trying to prime multiple paths of the adaptive immune system: the cellular pathway that recognizes infected cells and tells them to commit suicide, the humoral pathway that makes neutralizing antibodies that keep the virus from functioning, and the pathways in the mucosa that inactivate invaders and destroy infected cells.
As an additional complication, it’s trying to avoid activating a pathway that prompts a particular immune cell to ingest and destroy the virus. This is because the coronavirus, unusually, appears capable of ‘antibody-dependent enchancement’ - it can actually enter a cell that doesn’t express the ACE2 receptor, by hijacking the very process by which the cell is trying to destroy it! (The other virus where this is known to be significant is dengue - and the mechanism caused a disaster with the first campaign of dengue immunization. The vaccine reduced the incidence of the disease, but made the disease much more lethal if an immunized patient caught it.)
They’re also trying to avoid hyperstimulating the inflammatory pathways, since one of the manifestations of late-stage disease appears to be ‘cytokine storm’ in which the immune system essentially goes crazy and starts burning down everything in sight.
A further thing is that they’re trying to choose sequences that 2019-SARS-CoV–2 has in common with SARS and MERS - the fact that they’re conserved indicates that they’re likely to be critical to the virus function, and that the virus would have a hard time evading them by mutating. This is one thing that would be needed for long-term immunity!
Mucosal immunity is difficult to measure, but the effects can be observed. What we’re seeing here is that the prime dose of the vaccine does not elicit the head cold systems suggesting that the immune system has been immediately activated. When the booster is given, there are head cold systems, suggesting that there is specific cellular recognition of the peptides in the vaccine and an immediate inflammatory response. This is good news in that it indicates that, as you put it, ‘the vaccine is lighting up the right system.’ It’s also at least somewhat specific, since the researchers are doing nasal washes and swabs to sample mucosa, and these are not triggering symptoms.
In addition to trying to detect mucosal antibodies in nasal washing and saliva specimens, the researchers are trying to detect circulating antibodies associated with the humoral response. The cellular response is another aspect - perhaps the most critical in long-term immunity - that is difficult to measure. (We know that it’s important from the smallpox vaccine, in which many immune patients have low or negligible levels of circulating antibodies but mount a prompt and robust ‘take’ when they get a booster, indicating that they are indeed immune.)
This is one that I would take as a Phase 2 or Phase 3 subject. It’s pretty much 100% characterized as to what’s in it. (It’s not just ‘boil the virus until it can’t reproduce and then shoot the patient with everything’, which is pretty much how most vaccines are made.) There is zero viral genetic material in it. Everything except the peptides has been used before and has really low toxicity. The preliminary results show the subjects raising antibodies and a mucosal response. There’s really no ethical way to do a proper trial without a huge patient cohort, but if it comes to trying for a gray market vaccine, this is what I’d go for. (And as med-chem production goes, this one is dead easy - there are a bunch of specialized labs that could turn out the difficult materials in a few days, and with the peptides in hand, any compounding pharmacist could formulate it.
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Wow, thank you. That helped me tie together many things that I kinda sorta know about, such as the actual mechanism by which the dengue vaccine backfired.
Does that mean that various antibodies and stuff can directly read the RNA sequence of their potential victim? I thought antibodies had to rely on external proteins and such, and that the viral RNA was effectively inaccessible until transcription time. Or do you mean that they target external markers/proteins/whatever that are already known to directly correlate with those shared gene sequences?
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‘Sequences’ in this context meant ‘sequences of amino-acid residues’. The RNA is read out by the translation mechanism of the host cell and directly encodes for the protein to be made. There are modifications that enzymes make to both RNA and protein, but they’re relatively infrequent, and most of the coded-for amino acids are present in the same order in the protein as the three-base codons appeared in the RNA.
There are a handful of spots where the proteins fold in such a way that contiguous sequences are accessible to the immune system, and you can raise antibodies against those. (Other times, you need the detailed folded structure, which basically means the whole protein.) The researchers are betting that these short contiguous sequences, if they use enough of them (the current generation of the machine uses 19 separate fragments) will be recognized well enough for robust immunity.
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I know this was not the core of your response, but I want to jump on it as it relates to the discussion of rushing a vaccine. We have no good way to measure cellular response other than, can you catch the illness? It is relatively trivial to measure antibody titers, but we really do not understand the degree of protection they afford yet. For this reason, monitoring the phase 3 volunteers for a time to see if they contract covid after vaccination is pretty much the only determinant. Those vaccine candidates that made it past phase 2 are known to be able to generate antibodies (and to not cause immediate horrible side effects), but that may not indicate that they are actually protective. Challenge tests have been brought up a few times as a way to rush this (these consist of vaccinating the subject, verifying antibody titers, then intentionally trying to infect them with SARS-Cov-2. In the past, this has been performed on prisoners or patients in mental wards. For most of us in the field, there is an unavoidable horror at the thought of doing this.) In consideration of these facts, any vaccine candidate brought forth this year will very most probably not kill or injure you, but whether it will protect you will be an open question for a time.
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THURSDAY, SEPTEMBER 03, 2020
Must. Have. Sports.
It is certainly possible that concerns about the long term impacts of Covid are a bit overblown, but it seems pretty clear that it isn’t a trivial concern.
During a State College Area school board of directors meeting on Monday night, Wayne Sebastianelli — Penn State’s director of athletic medicine — made some alarming comments about the link between COVID-19 and myocarditis, particularly in Big Ten athletes. Sebastianelli said that cardiac MRI scans revealed that approximately a third of Big Ten athletes who tested positive for COVID-19 appeared to have myocarditis, an inflammation of the heart muscle that can be fatal if left unchecked.
“When we looked at our COVID-positive athletes, whether they were symptomatic or not, 30 to roughly 35 percent of their heart muscles (are) inflamed,” Sebastianelli said. “And we really just don’t know what to do with it right now. It’s still very early in the infection. Some of that has led to the Pac-12 and the Big Ten’s decision to sort of put a hiatus on what’s happening.”
by Atrios at 13:00
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Mind you, this is the same group of people who have no problem handing out permanent brain damage to kids in order to have their grotesquely overpaid “public” careers.
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Was prepared to rage on this based on the opening statement, but yes, that is in line with previous studies showing ~20% of recovered hospitalized patients (may be worse in kids, but numbers are too small to be reliable just yet) have compromised cardiac function due to covid myocarditis. “Long term” is very relative in a disease that is only 9 months old, but it is certaily concerning when it appears that we (USA) have gone for the “herd immunity” model.
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For circulating T cells, both memory and effector, we’re kind of close (it’s still controversial, and poorly standardized). Measuring Cellular Immunity to Influenza: Methods of Detection, Applications and Challenges - PMC
For the mucosal response, let’s just say that you’re entirely right - WDKS. And that one may be the most important of all, which is why I speculate that, despite the lackluster performance of the one intranasal flu vaccine that made it to the clinic, intranasal and intraoral vaccines may be the platform of the future for respiratory and digestive infections.
Even worse, in the past, we ran placebo-controlled challenge trials - infect the control group without trying to immunize them. Humans suck. (The Tuskegee syphilis experiment was even worse - coming close to Josef Mengele level!)
The jury is still out on the ethics of self-administered challenge trials. Would we have modern treatment of peptic ulcer disease if it weren’t for Barry Marshall? Would we have electrophysiology without Werner Frossmann? Still, no modern IRB would approve a self-administered trial, and no publication would accept its findings even as a case study (n=1) without IRB approval. (Part of this stems from the belief that a depressed researcher might use such a trial as a path to a particularly complicated suicide.)
(EDIT: Correct misspelt words.)
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Seriously SD, what are you doing?
“Republican Gov. Kristi Noem supported holding the rally in her state. “We are not – and WILL not – be the subjects of an elite class of so-called experts,” she tweeted in August. “We the People are the government.””
Oh “you” are an idiot.
On Aug. 7, the opening day of the rally, South Dakota had roughly 9,000 COVID-19 cases, according to the health department. By Sept. 3, positive cases had risen to 14,000. The state’s positivity rate also rose, from 6% for the 14 days before Aug. 7, to 15% for the 14 days before Sept. 3.
Yup, and your people reap what you sow. Burn in hell, you immoral harridan.
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