Was Merck doing a live attenuated virus technique?
Both are viral vector vaccines that use modified versions of other viruses to deliver instructions to cells.
Was Merck doing a live attenuated virus technique?
Obviously just need bellerophon.[icon] said:However, the differences in neutralization between the RBD-only chimera
I think we really need to see whether or not there are significant numbers of people in South Africa who have already had the standard COVID-19 are re-infected with the new strain. If not, we're good. If so, we need an updated Vaccine.[icon] said:Not sure if this study has been posted but it seems to indicate some potential issues with the South African strain?
Can smarter Medical folks than me break this down?
“When these same samples were assessed against the 501Y.V2 virus, nearly half (21 of 44, 48%) had no detectable neutralization activity, with only three samples (7%) retaining titres of ID50 >400 (Fig.2a-right). Notably, all three of these samples were obtained from individuals reporting severe disease who had some of the highest neutralization titres against the original virus.
To define the location of dominant escape mutations, neutralization was also assessed against the RBD chimeric viral construct containing only three 501Y.V2 mutations (K417N, E484K, N501Y) (Fig.2a-middle).
A substantial loss of neutralization was also observed against the RBD-only mutant, with 27% of the samples losing all activity against the RBD triple mutants, while only 23% retained higher titres of ID50 >400.
These data provide more evidence for the dominance of Class 1 and Class 2 neutralizing antibodies in polyclonal sera. However, the differences in neutralization between the RBD-only chimera and 501Y.V2 also highlight the contribution of 501Y.V2 NTD mutations (L18F, D80A, D215G, and Δ242-244) to neutralization escape. This was particularly evident in the higher titre samples, which retained an average titre of ID50 680 against the RBD-only mutant.”
I've been to Xiamen for business. I passed on the sea cucumbers at lunch... Ate everything else though.Just got an email from a vendor I do business with in China. They are in Xiamen City, China.
"We are going to start Chinese New Year(CNY) holiday end of this month/this week due to Covid-19 situation, workers will go home in earlier time.
There are some more new virus cases outbreak in the North of China places. We should be more care about it."
There's a warm fuzzy email a little over a year into this thing
Everywhere is plunging. As the Vax gets more and more rolled out these figures will continue to look better. Dallas is reporting full ICU but the hospital beds are opening up behind them suggesting the ICU bed issue will be self clearing.Covid cases PLUNGE and deaths down as UK confirms 6.6million receive first vaccine dose
THE UK has reported 22,195 coronavirus cases in the past 24-hours, a huge dip on figures in recent weeks.
Good to go on offense finally.Everywhere is plunging. As the Vax gets more and more rolled out these figures will continue to look better. Dallas is reporting full ICU but the hospital beds are opening up behind them suggesting the ICU bed issue will be self clearing.
This is over.
This is almost exactly 10% of the UK's population (66.5 million in 2019). The US needs to hit about 33-35 million vaccinations to reach the same level.Covid cases PLUNGE and deaths down as UK confirms 6.6million receive first vaccine dose
I think that's pessimistic. We have administered at least 1.3 million doses each of the last five days. Assuming that we can continue that pace, and that about a million a day currently are first jabs (we were doing about 300,000 shots per day three weeks ago, so that's an approximate number of people who will be getting jab2 daily), we should be doing close to a million first shots daily, with second shots increasing at the rate first shots increased over the past 3-4 weeks. Let's say we average 800,000 first shots over the next 20 days, that's 16 million on top of the 19 million or so who have received first shots so far (about 3.5 million have received both). That's mid february to get to 35 million with at least the first shot.This is almost exactly 10% of the UK's population (66.5 million in 2019). The US needs to hit about 33-35 million vaccinations to reach the same level.
At current pace ... looks like by the end of February here in the States?
Your math is right -- I was figuring "about a month", and that puts it around the last week of February.That's mid february to get to 35 million with at least the first shot.
Math is hard. Correct me if I'm wrong here.
That is what I'm worried about as well. Was told last week I would be contacted in 2-3 weeks to schedule my second dose, and I'm less than confident that they actually possess that dose currently. Just hoping they get restocked.Your math is right -- I was figuring "about a month", and that puts it around the last week of February.
I am concerned about the logisitic problems that have been cropping up locally (and I understand, in many other areas). Several hospitals and clinics cancelled vaccination appointments this week because they ran out of vials.
Great post, and a great reminder that now is not the time to get sloppy with prevention measures.Super sad story. I mentioned in passing one of my co-workers friend situation.
These are the stories that will stay with us. The deep and probably unspoken resentment of people taking calculated (stupid) risks, at the end of a pandemic. It will haunt alot of families for a long time. Don't be the last one to die in a war or a pandemic. Stay vigilant.
- Daughter goes to wedding (socially distant, right) comes back for Christmas.
- Dad flies to Florida to a retirement home! (yeah) notified daughter is + after visiting elderly father
- So elderly father gets in hospital and recovers without ICU stay, sent home maybe 10 days ago, but two days ago rushed to ICU with deep pneumonia and is not projected to make it.
I don't see what about this statement is politically related?Clickbait tag.
This divide is political, not racial in nature.
I feel like I explained my take on your bait pretty succinctly, however I'll get out the crayons and color it in a bit for you.I don't see what about this statement is politically related?
White people, the researchers found, were the least likely of any race to wear a mask consistently, with just 46 percent reporting that they wear one while in close contact with people they do not live with. That was compared with 67 percent of Black people, 63 percent of Latinos and 65 percent of people from other races.
I guess you can read it how you want. Whatever slant you want. Doesn't change the numbers one bit.
Not interested in discussing it if you just want to be a total **** about it. I have a different opinion of the data, I wasn't being confrontational. But apparently civil discussions aren't your thing. Have a nice day.I feel like I explained my take on your bait pretty succinctly, however I'll get out the crayons and color it in a bit for you.
Not sure I'd call race baiting "having civil discussions", but you do you.Not interested in discussing it if you just want to be a total **** about it. I have a different opinion of the data, I wasn't being confrontational. But apparently civil discussions aren't your thing. Have a nice day.
Snow days are effectively over. They are no longer needed and what you described will likely be the norm for the foreseeable future.Don't want to try and search for the school Covid thread, so I will post here. Forecast was that we should get 5"-8" between this evening and tomorrow. At 7pm my wife got an auto email/phone call from the school that tomorrow will be a "snow day" and that all students should do their hydrid/remote schedule. Our kids were already on a Mon/Thurs schedule so no change for them. As of 11pm we have maybe 1.5" of snow. Seems like the school used the already in place remote schooling as a way to have everyone go remote at the thought of a massive snow. I hope if we actually get a massive storm that our schools give the kids a real snow day. Don't need to get several calls from my wife complaining that the kids are wanting to go outside instead of doing online school.
Probably the same number that would have if they ran the commercial.Budweiser Skips Super Bowl Ad, Promises Vaccine Education Instead
But how many will change beer brands over this?
What classification are you?FWIW Texas sites are opening up the wait lists and registrations, got notified in an adjacent county I'm looking at June 4th. #progress?
Monoclonal antibodies yet to show important clinical benefit in patients with covid-19. A review of what we know, including the latest clinical trial data.
One of the many challenges of the covid-19 pandemic has been the lack of targeted therapeutics. Extensive efforts have been invested into research with only glimmers of benefit for most drugs. The exception to this has been dexamethasone which was shown in the RECOVERY trial to have remarkable impacts on death in patients requiring oxygen and in those requiring invasive mechanical ventilation. Other drugs, some of which showed varying degrees of promise in observational and retrospective studies (from hydroxychloroquine to convalescent plasma) have largely fizzled in randomized trials, while fancier newer drugs, namely remdesivir, have generated inconsistent (and certainly disappointing) results, at best.
Monoclonal antibody infusions have gained national attention as a potential therapeutic in covid-19 patients. The hype in part comes from some medical experts touting them. Part of the optimism about this class of drugs comes from the elegance of how they are supposed to work. By design, these molecules bind to specific “domains” of the SARS-CoV-2 spike protein, thereby blocking its ability to bind to receptors on human cells and thus, it is hoped, stopping cellular invasion and cutting off the virus’ “life cycle.”
Let’s review how well these molecules work “in real life.” The ACTIV-3 trial, published in December 2020, found no benefit to hospitalized patients receiving bamlanivimab (the Eli Lily product also known as LY-CoV555) along with remdesivir. Since then, the focus has shifted to treating non-hospitalized patients. There is logic to this shift; once patients are sick enough to require hospitalization, they are likely out of the so-called “viral phase” of illness. So, clearing the virus from the body is no longer relevant. At that point, the body is busy generating polyclonal antibodies (i.e. antibodies that target a number of different parts of the virus) in response to infection; adding a monoclonal antibody infusion is unlikely to help beyond this point. All of this explains the emphasis on delivering monoclonal antibodies to covid-19 patients early.
The two major opportunities to assess this are the BLAZE-1 (Eli Lily) and REGN-CoV2 (Regeneron) trials. An interim analysis of BLAZE-1 (published in October, 2020) demonstrated a small reduction in viral load with one of the three studied doses of bamlanivimab (another name for LY-CoV555) when given to patients early in their disease (a median of four days from symptom onset). However, this difference fell below the author’s preset threshold and raised questions around the biological plausibility of the endeavor, as only the middle dose (2800 mg) showed a viral load reduction. (Treatments that work well often have a “dose-response” curve, meaning that within a certain range, higher doses correlate to more measurable changes; these findings went against that). Even putting methodological shortcomings aside, a reduction in viral load alone is meaningless to the patient as it is not a clinical outcome. Viral loads only matter if they correlate to outcomes patients might notice, such as the severity and duration of their symptoms, or whether there is a change in mortality. Despite these lackluster findings, bamlanivimab (LY-CoV555) was granted Emergency Use Authorization by the US Food and Drug Administration. Since then, thousands of patients have been referred to infusion centers and emergency departments to receive this therapy.
The REGN-CoV2 Trial data (published in December, 2020) investigated infusion of two monoclonal antibodies (known as casirivimab and imdevimab) to outpatients early in their covid-19 disease course. The monoclonal antibody cocktail was used in an effort to reduce the emergence of treatment-resistant virus mutations. Similar to the BLAZE-1 group, the REGN-CoV2 investigators reported a reduction in viral load with this treatment. However, the methodological flaws of this study were considerable, including the fact that the group did “no formal hypothesis testing.” This means that the trial amounted to a fishing expedition to find a benefit. Rigorous and reliable studies test one or two very focused questions. Nevertheless, the cocktail was also granted Emergency Use Authorization by the US FDA and and has been administered to thousands of patients based on virtually non-existent data, despite no clinically meaningful benefit for patients. One key finding did emerge from this study though: 45 percent of patients enrolled already had SARS-CoV-2 antibodies prior to the administration of the cocktail even though the researchers had gone out of their way to find patients who were still early in their disease course. Thus, the available evidence does not support the use of the REGN-CoV2 monoclonal antibody cocktail.
The past week, the complete dataset for the BLAZE-1 trial was published in JAMA. The study assessed bamlavinimab (LY-CoV555) as well as a dual monoclonal antibody therapy of bamlavinimab and another antibody, etesvimab. Interestingly, the benefit for the 2800 mg dose of bamlavinimab monotherapy reported in the BLAZE-1 interim report has disappeared in the final report. Thus, there is now no clinical trial data supporting bamlavinimab by itself with respect either to a clinical benefit, nor even for proxy outcomes like viral load reduction.
But what about the combination therapy? As before, there is evidence that viral load reductions occurred, albeit the reduction was smaller than the threshold that had been prespecified as meaningful by the researchers. The study also included a whopping 84 “secondary endpoints.” Secondary endpoints are findings that trials were not designed to study but which were measured nonetheless—usually in an attempt to discover any hidden benefits or harms that a treatment may offer. One such finding was a reduction in hospitalization or emergency department visits. This finding was seen in two groups of test subjects who received bamlavinimab alone as well as in the group of patients who received that and etesvimab. However, there were wide confidence intervals (meaning that the range of possible outcomes was large), the number of ER visits and hospitalizations were low (meaning a small number of different outcomes could have had enormous impact on the findings), and no granular data on whether the reductions were in ER visits or in hospitalization (which, of course, are rather different). At best, this finding is hypothesis generating only.
It should also be noted that we have limited safety data for these drugs. Though none of the studies revealed a significant number of serious adverse events, the studies are not large enough to establish safety.
At this point, there is no convincing data that designed monoclonal antibodies that target SARS-CoV-2 improve meaningful outcomes in covid-19 patients, either alone or in a “cocktail” of antibodies. As mentioned, the idea of treating established covid-19 patients with monoclonal antibodies may itself be a flawed paradigm as even patients with early disease are likely to have already generated sufficient antibodies (as seen in the REGN-CoV2 study) that adding more to the body intravenously is like adding salt to an ocean. Additionally, we don’t know the effect of monoclonal antibody infusions on vaccine efficacy. Despite emergency authorization for bamlavinimab and the Regeneron cocktail, at this time, these treatments should only be given in the setting of a randomized controlled clinical trial designed to evaluate outcomes that patients would notice. The BLAZE-2 trial currently underway is investigating the use of monoclonal antibodies for prophylaxis. This effort may be more promising, though vaccines are likely to be far more effective in this role.
While clinicians feel the need to do something for patients early in their disease process to prevent progression to more severe illness, this need does not justify giving a treatment with unproven benefits—and with mounting proof that there is little to none to be had.
The article linked doesn't answer this squarely: What, exactly, does a "sixfold reduction" mean here? From ~95% effective to ~16% effective? 1/6 the number of antibodies per unit of blood? Something else? The article says exactly this:Moderna’s vaccine is less potent against one coronavirus variant but still protective, company says
tl;dr: Scientists found that there was a 6x reduction in the vaccine’s neutralizing power against the South African variant, but still above levels ruling it "effective;"
The announcement from Moderna gets at a nuance that scientists have been trying to stress as fears around vaccines and variants grew. Both the Moderna vaccine and the immunization from Pfizer-BioNTech produce such powerful levels of immune protection — generating higher levels of antibodies on average than people who recover from a Covid-19 infection have — that they should be able to withstand some drop in their potency without really losing their ability to guard people from getting sick.
“There is a very slight, modest diminution in the efficacy of a vaccine against it, but there’s enough cushion with the vaccines that we have that we still consider them to be effective,” Anthony Fauci, the top U.S. infectious diseases official, said Monday on the “Today” show.
Yeah, didn't understand that either. Obviously 16% would be well below the "effective" threshold. Could just be a count of some sort that's used in calculating the effectiveness. Not sure.The article linked doesn't answer this squarely: What, exactly, does a "sixfold reduction" mean here? From ~95% effective to ~16% effective? 1/6 the number of antibodies per unit of blood? Something else? The article says exactly this:
Good question -- my skin crawls when people write stuff like this. Where is a science/math editor when you need one?The article linked doesn't answer this squarely: What, exactly, does a "sixfold reduction" mean here? From ~95% effective to ~16% effective? 1/6 the number of antibodies per unit of blood? Something else? The article says exactly this:
This was a lab test only, not in-vivo. It looked at antibodies produced from people that have had the Moderna vaccine and the ability of those antibodies to fight the virus (in a test tube). The % reduction in efficiency of the vaccine produced antibodies against this variant is unlikely to translate exactly to the same % reduction inside the human body.Good question -- my skin crawls when people write stuff like this. Where is a science/math editor when you need one?
This is stupid, but my guess is that what the author means is that the current vaccine is 95% effective / 5% "ineffective." That "sixfold reduction" means multiplying that 5% figure times six to get you to 70% effectiveness. Is that an intelligent way of expressing something along those lines? No of course not. But it would at least be consistent with "not as effective, but still above the 50% threshold."
But really, the reader shouldn't have to guess what specific error the author is making.
Really wish they'd have kept their slots and used those commercials for vaccine education instead. Would've reached more people. Still... good for them.Budweiser Skips Super Bowl Ad, Promises Vaccine Education Instead
But how many will change beer brands over this?
This.This was a lab test only, not in-vivo. It looked at antibodies produced from people that have had the Moderna vaccine and the ability of those antibodies to fight the virus (in a test tube). The % reduction in efficiency of the vaccine produced antibodies against this variant is unlikely to translate exactly to the same % reduction inside the human body.
A lot of that is due to the significant effectiveness of these antiobdies vs. other variants, which were absolutely crushing it.
From the paper: https://www.biorxiv.org/content/10.1101/2021.01.25.427948v1
"VSV pseudoviruses with spike containing K417N-E484K-N501Y-D614G and full B.1.351 mutations resulted in 2.7 and 6.4-fold GMT reduction, respectively, when compared to the D614G VSV pseudovirus. Importantly, the VSV PsVN GMT of these human sera to the full B.1.351 spike variant was still 1/290, with all evaluated sera able to fully neutralize."
This is probably true? Why didn’t they think of that.Really wish they'd have kept their slots and used those commercials for vaccine education instead. Would've reached more people. Still... good for them.
And the worst part is ... most readers will make the mental leap straight to "The vaccines WILL NOT WORK on the South African strain!!!11!". I mean, for many readers, Bill Pullman basically shows up at your hose ranting "Game over, man!"Good question -- my skin crawls when people write stuff like this. Where is a science/math editor when you need one?The article linked doesn't answer this squarely: What, exactly, does a "sixfold reduction" mean here? From ~95% effective to ~16% effective? 1/6 the number of antibodies per unit of blood? Something else? The article says exactly this:
Well, at least the article did quote Fauci and another expert making that point. But you know how a lot of people parse news. SIX-FOLD DECREASE! VACCINES DON'T WORK ANYMORE! SCIENCE SAYS SO!!!They seem to be making it clear that they still expect the response to be sufficient to neutralize the new strain.
I think that's what they were trying to cover with the "but still protective" part of the title, but yeah, def could've been worded a little better for clarity.Well, at least the article did quote Fauci and another expert making that point. But you know how a lot of people parse news. SIX-FOLD DECREASE! VACCINES DON'T WORK ANYMORE! SCIENCE SAYS SO!!!
Ham had his account deleted, he posted a lot early in the thread.Seems like we've lost a few pages here, wonder where all the posts went..... did I miss something?
Anyways, good to hear folks are out getting vaccinated. That's a positive.
California is shut down pretty hard right now. Cases have spiked hardcore since November.
I am so over this. :(
Do you mean "deleted intentionally", like he asked the mods to dump all of his posts?Ham had his account deleted, he posted a lot early in the thread.