CraigM
1789
Reading Andy Weir’s latest book and came across this paragraph today
I had wondered about this previously. Those antigens still have to bind to a receptor to enter cells.
Makes perfect sense. Cool that sort of thing is being looked at.
Hope to listen to this tomorrow
Houngan
1791
Wouldn’t an mRNA and a more traditional vaccine do roughly the same thing? One for the spike, one for the payload? Seems like there was somewhere that they mixed in AZ or J&J.
jsnell
1792
Neither AZ or J&J is a traditional vaccine in that sense. They’re both using an adenovirus as a vector, except the virus has been modified to include gene for the Covid spike protein. I.e. they should also just produce a response to the spike, not the rest of Covid.
Houngan
1793
Ah, thanks for the correction/clarification.
This week’s TWiV clinical update. It’s the shortest and generally the most useful update to listen to.
Just listened to the one that you linked to a week ago. Super great discussion!
Antibodies that turn against elements of our own immune defences are a key driver of severe illness and death following SARS-CoV-2 infection in some people, according to a large international study. These rogue antibodies, known as autoantibodies, are also present in a small proportion of healthy, uninfected individuals — and their prevalence increases with age, which may help to explain why elderly people are at higher risk of severe COVID-19.
“There is a massive increase in prevalence” with age, Casanova says. “This largely explains the high risk of severe COVID in people in the elderly population.” He adds that these findings have clear clinical implications, and suggests that hospitals should be checking patients for these autoantibodies, as well as mutations implicated in blocking type 1 interferons. This could identify people who are more likely to become critically ill from COVID-19, helping physicians to tailor their treatment appropriately.
A sample of more than 30,000 people is “too big to ignore”, according to Ring. “It just shows that this is something that we need to think about.” He adds that researchers should now consider whether autoantibodies play a part in driving other infectious diseases. Ring’s team has already found evidence 5 of autoantibodies against various immune-system components in people with COVID-19, and he and his colleagues are now investigating further. “I suspect that we’ve just started scratching the surface,” Ring says.
https://www.nature.com/articles/d41586-021-02337-5?utm_source=Nature+Briefing&utm_campaign=6ef11059c6-briefing-dy-20210901&utm_medium=email&utm_term=0_c9dfd39373-6ef11059c6-46586826
CraigM
1797
very interesting. Since you are in the field Jim, maybe you know. Is this type of immune cell something previously identified, or something only recently discovered?
Because if this is a newly identified feedback system within our immune response it seems the COVID research could yield benefits far outside of that scope.
Only vaguely in the field, in the same way that a cobol programmer and an engineer developing cloud architecture are both “programmers”.
Autoantibodies aren’t a new thing, but the interactions with infectious disease seem to be. There’s some hope that the next step is looking for genetic determinants of these antibodies, so we can better predict disease severity and know who needs early intervention.
I was going to do a writeup of this, but I’m going to cheat and use our comms team science writers summary of this paper:
Antiviral therapy targets the virus itself, but another approach, called host-directed antiviral therapy, targets host responses that promote infection. In Nature Communications, Francisco Quintana and collaborators identified a possible therapeutic target for this approach: the aryl hydrocarbon receptor (AHR). The team found increased AHR signaling in human cells infected with multiple coronaviruses as well as in nasal swabs and lung cells from SARS-CoV-2-infected patients. Bioinformatic analyses of RNA expression identified AHR as a regulator of the cellular response to infection. Moreover, pharmacologic inhibition of AHR in human cells interfered with replication of SARS-CoV-2 and HCoV-229E, a coronavirus associated with the common cold.
Pretty interesting to identify a factor in humans that some viruses turn on to evade/down-regulate human immune response, and that identification gives us targets to fight back. Bonus for this being common across a number of other viruses, so we’re learning tools that may have impact for the next pandemic.
Several drugs with antiviral activity against SARS-CoV-2 have been tested in vitro and in ongoing human studies68. However, viral-directed drugs such as lopinavir, ritonavir, and remdesivir seem to be ineffective in treating SARS-CoV-2 14 days after symptoms onset69,70, highlighting the need to identify additional therapeutic approaches. Host-directed antiviral therapy aims to target host factors that participate in virus replication. It has been postulated that this approach is less likely to select drug-resistant virus strains, although drug resistance against host-directed agents has been documented71. Most importantly, since host factors are usually shared by multiple viruses, antiviral drugs targeting a common host factor are expected to show a broader spectrum of action72,73. Based on its effects on the antiviral response17,18,19, AHR is an attractive candidate target for host-directed antiviral therapy. Indeed, using an in vitro approach, we showed that the AHR antagonist CH223191 reduced HCoV-229E and SARS-CoV-2 replication.
An interesting thread from Trevor Bedford summarizing the current state of things.
I haven’t heard anything about the delta specific vaccine booster lately, but Trevor makes a strong case that it’s needed.
I do think declaring “peak!” is premature, though.
I might even say he’s daring the universe by declaring such a thing!
Yes. I felt that the lesson we learned (or should have learned) last year was that the USA is large enough and it’s population centers separated enough that it doesn’t really experience a single national epidemic - more like multiple regional epidemics that don’t happen at the same time.
Edit: so national-level statistics are missing a large part of the story.
It’s supported by the “back of the napkin” math he did back a few months ago, as noted in that thread. At the time, I’d hoped 36 million cases was an overestimate, now I’m afraid it might be well under.
Calelari
1805
Particularly with college football just starting up. Last Saturday was first home game here. Full stadium, not a mask in sight, lots of people come in from out-of-town. And this wasn’t even a big deal of a game - next home game in two weeks is vs. 'Bama. Yay.
Interesting read, thanks for posting it. It does feel like the “novel” element of all this has been lost in recent discussions, presumably the greatest strength of the vaccines is making a once novel virus no longer novel. I knew nothing about the particulars of kids’ immune systems, so it’s fascinating to get a glimpse as to how all that works.
Of course, this can only be worrying:
As the pandemic wears on, researchers worry that the virus could evolve in ways that thwart some part of kids’ innate protection. Some researchers have found that the Alpha variant, which was dominant in some parts of the world for a time, developed tricks that allowed it to suppress the body’s innate immune response. They worry that Delta could do the same. For now, increased hospitalizations of children in regions where Delta is circulating seem to be the result of its enhanced infectivity across all ages, coupled with the fact that many adults are vaccinated or have already been infected with SARS-CoV-2. But researchers are watching carefully.
Here’s hoping we’re able to get kids vaccinated before that particular pile of fecal matter hits the fan.
I’ve been thinking about that as well. NFL too this week. Just school being back could be a bigger factor.
vinraith
1808
An interesting thread on a recent (not yet peer-reviewed) study of CoV-2 mutation rates. This, if it bears out, looks like bad news to my eye. I’d previously understood the need for annual boosters to be unlikely, but this thing is (at least right now, while still adapting to a new host and raging through a large population) mutating faster than a typical flu virus.
I’m not really bothered by getting a Covid booster every year, I was just hoping we wouldn’t need 'em.
