COVID-19 Vaccine Progress: Are We Ready for Rollout in Australia?

[Ygggdrasil]

The South African decision to not give the Oxford vaccine is IMHO mad. They had the vaccine - why not deploy it.

Because preliminary studies suggest that the vaccine is not effective against the B.1.351 variant that is the predominant variant in the country:

Safety and efficacy of the ChAdOx1 nCoV-19 (AZD1222) Covid-19 vaccine against the B.1.351 variant in South Africa
https://www.medrxiv.org/content/10.1101/2021.02.10.21251247v1

Abstract:

Background Assessing safety and efficacy of Covid-19 vaccines in different populations is essential, as is investigation of efficacy against emerging SARS-CoV-2 variants of concern including the B.1.351 (501Y.V2) variant first identified in South Africa.
Methods We conducted a randomized multicentre, double blinded controlled trial on safety and efficacy of ChAdOx1-nCoV19 in HIV-uninfected people in South Africa. Participants age 18 to <65 years randomized (1:1) to two doses of vaccine containing 5×1010 viral particles or placebo (0.9%NaCl) 21-35 days apart. Post 2nd-dose serum samples (n=25) were tested by pseudotyped (PSVNA) and live virus (LVNA) neutralization assays against the D614G and B.1.351 variants. Primary endpoints were safety and vaccine efficacy (VE) >14 days following second dose against laboratory confirmed symptomatic Covid-19.
Results 2026 HIV-uninfected adults were enrolled between June 24th and Nov 9th, 2020; 1010 and 1011 received at least one dose of placebo or vaccine, respectively. Median age was 31 years. The B.1.351 variant showed increased resistance to vaccinee sera using the PSVNA and LVNA. In the primary endpoint analysis, 23/717 (3.2%) placebo and 19/750 (2.5%) vaccine recipients developed mild-moderate Covid-19; VE 21.9% (95%Confidence Interval: −49.9; 59.8). Of the primary endpoint cases, 39/42 (92.9%) were the B.1.351 variant; against which VE was 10.4% (95%CI: −76.8; 54.8) analyzed as a secondary objective. The incidence of serious adverse events was balanced between the vaccine and placebo groups.
Conclusions A two-dose regimen of ChAdOx1-nCoV19 did not show protection against mild-moderate Covid-19 due to B.1.351 variant, however, VE against severe Covid-19 is undetermined.

 

[Ygggdrasil]

Also of possible importance I did hear a garbelled report on the late news last night that the UK has verified, with the WHO soon to follow, that Ivermectin does have efficacy in Covid prevention and early phase treatment, and will be recommended in that role. If true, when combined with pretty much any of the vaccines, it will hit Covid hard.

A randomized clinical trial of ivermectin was recently published showing that ivermectin had no effect on speeding recovery from COVID-19:

Early administration of the antiparasitic drug ivermectin didn't significantly shorten time to clinical improvement in 400 adults mildly ill with COVID-19, a clinical trial today in JAMA finds.

Led by researchers from the Centro de Estudios en Infectologia Pediatrica in Cali, Colombia, the single-center, double-blind, randomized trial used random sampling of coronavirus-positive patients to identify inpatients and outpatients with mild COVID-19 within the first 7 days after symptom onset from Jul 15 to Nov 30, 2020.

Median time to symptom resolution was 10 days in the 200 patients randomly assigned to receive ivermectin daily for 5 days, compared with 12 days in 198 patients receiving a placebo (interquartile range for both, 9 to 13 days; hazard ratio, 1.07).

Here's the published, peer-reviewed paper describing the study:

Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19: A Randomized Clinical Trial
https://jamanetwork.com/journals/jama/fullarticle/2777389

Abstract:

Importance Ivermectin is widely prescribed as a potential treatment for COVID-19 despite uncertainty about its clinical benefit.

Objective To determine whether ivermectin is an efficacious treatment for mild COVID-19.

Design, Setting, and Participants Double-blind, randomized trial conducted at a single site in Cali, Colombia. Potential study participants were identified by simple random sampling from the state’s health department electronic database of patients with symptomatic, laboratory-confirmed COVID-19 during the study period. A total of 476 adult patients with mild disease and symptoms for 7 days or fewer (at home or hospitalized) were enrolled between July 15 and November 30, 2020, and followed up through December 21, 2020.

Intervention Patients were randomized to receive ivermectin, 300 μg/kg of body weight per day for 5 days (n = 200) or placebo (n = 200).

Main Outcomes and Measures Primary outcome was time to resolution of symptoms within a 21-day follow-up period. Solicited adverse events and serious adverse events were also collected.

Results Among 400 patients who were randomized in the primary analysis population (median age, 37 years [interquartile range {IQR}, 29-48]; 231 women [58%]), 398 (99.5%) completed the trial. The median time to resolution of symptoms was 10 days (IQR, 9-13) in the ivermectin group compared with 12 days (IQR, 9-13) in the placebo group (hazard ratio for resolution of symptoms, 1.07 [95% CI, 0.87 to 1.32]; P = .53 by log-rank test). By day 21, 82% in the ivermectin group and 79% in the placebo group had resolved symptoms. The most common solicited adverse event was headache, reported by 104 patients (52%) given ivermectin and 111 (56%) who received placebo. The most common serious adverse event was multiorgan failure, occurring in 4 patients (2 in each group).

Conclusion and Relevance Among adults with mild COVID-19, a 5-day course of ivermectin, compared with placebo, did not significantly improve the time to resolution of symptoms. The findings do not support the use of ivermectin for treatment of mild COVID-19, although larger trials may be needed to understand the effects of ivermectin on other clinically relevant outcomes.

 

[Tom.G]

Intervention Patients were randomized to receive ivermectin, 300 μg/kg of body weight per day for 5 days (n = 200) or placebo (n = 200).

The one video I've watched pushing Ivermectin used 7 to 10 times that dose.
The presenter comes across as pushing his favorite Miracle of the Day, but if the data is real it may be worth further investigation.

The first part gives some background on what is currently in use, especially for 'Long Haulers.'
The 'Hard Data' start around the 43:00 mark

Dr. Pierre Kory, Ivermectin, and COVID (Let’s help end the pandemic.)


Cheers,
Tom

 

[bhobba]

The one video I've watched pushing Ivermectin used 7 to 10 times that dose.
The presenter comes across as pushing his favorite Miracle of the Day, but if the data is real it may be worth further investigation.

It's one of those things that polarises people, like HCQ did. Well designed trials are underway, but not yet completed, that will answer the questions one way or the other:
https://www.the-scientist.com/news-...ersial-ivermectin-paper-pre-publication-68505

And 300 μg/kg of body weight for the Ivermectin is actually slightly higher than what the I-Mask+ protocol use which is 200 ug/kg. It usually in practice equates to a 6mg tablet morning and night.

At the moment all we can really say is the NIH changed its recommendation from not recommended except in trials to neutral. But the options are very limited as far as early treatment goes. Telling people to go home and take some paracetamol is not very reassuring. With the neutral recommendation there is little harm in trying it, and I personally have have checked my GP is willing to prescribe the 5 daily dose regime as early as possible if I get it as per the I-Mask+ protocol. I already take all the other stuff of that protocol such as Quercetin. Again 'ironclad' evidence (except for vitamin D) they are of any value is not available. I am not even sure if other things we have now found out, such as being deficient in Vitamin D is a significant risk factor, is just as efficacious. I still think getting a physical that includes checking vitamin D levels, sugar levels etc, based on our current knowledge, is the best course of action while waiting for the vaccine. You can discuss other things like Quercetin, Ivermectin etc with your doctor at the same time.

The good news is, as per a previous post, we now have large scale data from the UK on the Oxford and Pfizer vaccine. Even after just one dose, after about 30 days of either vaccine, it is 80% effective in preventing hospitalizations in older and at risk groups, and that is with the more virulent UK variant. Scotland has vaccinated 21% of its population and is further down the rollout than the UK as a whole. It's data was even better with 85% prevention for Pfizer and 94% for Oxford.
https://publichealthscotland.scot/n...-in-risk-of-covid-19-admissions-to-hospitals/

Strangely the Oxford vaccine, with just one dose, is even more effective at preventing hospitalisations than Pfizer. We eagerly await the data once everyone is vaccinated with two doses. The UK rolled the dice and decided to vaccinate everyone with just one dose before administering the second dose and the gamble seems to have paid off. Pure dumb luck IMHO - sometimes it works in your favor - but I am not a fan.

Thanks
Bill

 

[bhobba]

You can criticize what others are doing - so let's hear your worldwide rollout plan. To which countries would you send the vaccines and why?

I think it depends on public mood. PNG was a former Australian protectorate famed here in Aus for its fuzzy wuzzy angels that saved many lives on the Kokoda Trail in WW2. They are in dire need of Covid help. Knowing how Australians feel about them, despite how cosy they are becoming with China, without hesitation an Australian emergency medical team was sent in, and they will be getting priority access to the Oxford vaccine we are making and being distributed from the 22nd. First is the islands between PNG and Australia (some part of Aus - some part of PNG) - then PNG proper. I guess even with public good will the first consideration is stopping it on islands that can reach Australia first - so we are not entirely altruistic.

Thanks
Bill

 

[bhobba]

Interesting, thanks. That must be it -- sure is a confusing point on their own web page!

As my stats professor said - statistics is like a bikini - it's the bits you don't see you want to know about. Sexist and politically incorrect - but he was still a funny guy.

Thanks
Bill

 

[berkeman]

It looks like some great apes and other zoo animals are starting to receive a vaccine intended just for animals now. Does anybody know what they mean by "intended strictly for non-human use"?

https://www.cnn.com/2021/03/05/us/great-apes-coronavirus-vaccine-san-diego-zoo-trnd/index.html

(CNN) -- Several great apes at the San Diego Zoo have been vaccinated against Covid-19 a few weeks after the zoo's gorillas tested positive for the virus.

Members of the zoo's bonobo and orangutan troops were vaccinated using doses from a supply intended strictly for non-human use, the San Diego Zoo Wildlife Alliance (SDZWA) said in statement to CNN.

 

[Ygggdrasil]

The good news is, as per a previous post, we now have large scale data from the UK on the Oxford and Pfizer vaccine. Even after just one dose, after about 30 days of either vaccine, it is 80% effective in preventing hospitalizations in older and at risk groups, and that is with the more virulent UK variant. Scotland has vaccinated 21% of its population and is further down the rollout than the UK as a whole. It's data was even better with 85% prevention for Pfizer and 94% for Oxford.
https://publichealthscotland.scot/n...-in-risk-of-covid-19-admissions-to-hospitals/

Strangely the Oxford vaccine, with just one dose, is even more effective at preventing hospitalisations than Pfizer. We eagerly await the data once everyone is vaccinated with two doses. The UK rolled the dice and decided to vaccinate everyone with just one dose before administering the second dose and the gamble seems to have paid off. Pure dumb luck IMHO - sometimes it works in your favor - but I am not a fan.

Here's a link to the non-peer reviewed pre-print study cited by the Public Health Scotland site you linked to:

Effectiveness of First Dose of COVID-19 Vaccines Against Hospital Admissions in Scotland: National Prospective Cohort Study of 5.4 Million People
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3789264

Here's the relevant quote from the papers findings:

The first dose of the BNT162b2 vaccine was associated with a vaccine effect of 85% (95% confidence interval [CI] 76 to 91) for COVID-19 related hospitalisation at 28-34 days post-vaccination. Vaccine effect at the same time interval for the ChAdOx1 vaccine was 94% (95% CI 73 to 99).

With BNT162b2 referring to the Pfizer-BioNTech vaccine and ChAdOx1 referring to the Oxford-AstraZeneca vaccine.

A few notes:
1) While the point estimate of the vaccine efficiency (VE) for the Oxford vaccine in preventing hospitalizations is higher than the VE of the Pfizer vaccine, the confidence intervals of the estimates overlap considerably, so the study does not provide evidence for a statistically significant difference between the two vaccines.

2) The study is an observational cohort study and not a randomized controlled trial. Because people were not randomized to receive the Ofxford or Pfizer vaccine, there are differences in the populations who received each vaccine (e.g. see the differences in the age distributions for the two vaccines in Fig 2 of the manuscript), which make it difficult to directly compare the observed VE for the two vaccines.

3) The study looked only at hospitalizations at 28-34 days post-vaccination, which is a very short time period after vaccination. More long term data (which is where one might expect to see differences between one dose vs two doses) is needed to assess whether delaying the second dose is ultimately a good idea or not.

 

[bhobba]

The study looked only at hospitalizations at 28-34 days post-vaccination, which is a very short time period after vaccination. More long term data (which is where one might expect to see differences between one dose vs two doses) is needed to assess whether delaying the second dose is ultimately a good idea or not.

Interestingly, when you look at the video I posted, that carefully goes over the UK data (not just Scotland) what they found is in the first 9 days after vaccination the odds of getting Covid rose 48%. I do not think anybody as yet is 100% sure why (again further research is needed) but the hypothesis is people when vaccinated went whoopee - and stopped taking precautions. So people are well advised to keep up the precautions until it has a chance to have maximum effect, which for the Oxford was 75% efficacy at 35 days. So I would wait at least that long before reducing precautions. In fact I would wait until everyone has had the second dose, but that's just me.

Thanks
Bill

 

[Laroxe]

Just a few thoughts.
When we see the headlines about vaccine efficiency the figures don't really say much about an individuals risk, there are lots of variables that effect risk and this means it is virtually impossible to say we get 100% protection. So what we see are risk estimates at a population level, its a statistical measure of relative risk. We can get the relative risk (RR) of infection, the RR of developing serious disease, the RR of dying the RR of being able to transmit the infection etc and for each of these the numbers will be different and they will change over time. The figures usually come from the phase 3 trials where you get thousands of people give half the vaccine and half a placebo then let them loose into the wild, as it were. After some predetermined end point, usually the number of people diagnosed with the disease, at a particular point in time, you can then compare how many people in the vaccine group and how many in the control group became infected. If everything was equal the RR would be expressed as 1 so you start with 1 and subtract any difference seen in the numbers from the vaccine vs the control group. In the moderna trial they had around 30,000 subjects, 15,000 in each group and when 95 people in the 30,000 had developed the infection they found only 5 were in the vaccine group the other 90 were in the control group.

So its 1 - 5/90 which through the magic of statistics is 94.44% efficiency, this figure is most useful in estimating the population level immunity and numbers needed to stop the disease. Remember this is not a fixed number, it will change.

Over time it will be impossible to conduct Placebo controlled trials, we will have to rely more on observational studies.

The discussions about ivermectin seem a bit pointless now, if it does have an effect its a small one, we shouldn't be torturing the data to try and find one. The US are using monoclonal antibodies which do help if given early, these are of course expensive drugs so its difficult to know how widely they will be adopted, I'm not even sure about their use in the uninsured in the US.

There are certainly differences in the mRNA vaccines and the viral vector vaccines both in their adverse events and the timing of the development of immunity but so far they all look very good. The big question that needs answering is how enduring the immunity is.

In the argument between the EU and Astra Zenica over their production problems (shared with Pfizer and Moderna) but in Astra Zenica's case linked with Brexit, EU politicians have inadvertently provided a real world experiment in preventing effective vaccinations programs. Following several politicians attacking the A.Z. vaccine effectiveness there appears to be a general reluctance to accept this vaccine and despite the shortage their are stockpiles being unused. While the ill informed statements have been retracted, so far this has had little impact, it does put the concerns about misinformation on social media into perspective.

 

[Ygggdrasil]

Interestingly, when you look at the video I posted, that carefully goes over the UK data (not just Scotland) what they found is in the first 9 days after vaccination the odds of getting Covid rose 48%. I do not think anybody as yet is 100% sure why (again further research is needed) but the hypothesis is people when vaccinated went whoopee - and stopped taking precautions. So people are well advised to keep up the precautions until it has a chance to have maximum effect, which for the Oxford was 75% efficacy at 35 days. So I would wait at least that long before reducing precautions. In fact I would wait until everyone has had the second dose, but that's just me.

Here's some relevant data from the Scotland paper:
Overall, 7-13 days after the first vaccine dose (either Pfizer or Oxford), they observed a 47% protection COVID-19 from hospitalization (see Table 2). However, there is a difference when the data are split by age group. For ages 65-79, the vaccine efficiency was 62% 7-13 days after the first dose and 67% for those age >80. However, the vaccine efficiency 7-13 days after the first does for those ages 18-64 was -36% (meaning more people were hospitalized for COVID-19 7-13 days after vaccination compared to the general unvaccinated population). The fact that only the younger age groups show a negative vaccine efficiency does support the hypothesis that young people are prematurely stopping precautions after getting vaccinated.

 

[Klystron]

After being too young by one year for the initial public vaccine program in southern Nevada USA, I received the Pfizer vaccine first dose this week at our local veteran's hospital after minimum age reduction from 70 to 65 years old. Second dose scheduled in 21 days.

Online vaccination registration in the three modes I attempted -- local pharmacies, public health centers and veteran affairs (VA) -- required scheduling both injections in order to receive the first. Some local pharmacies indicated available first doses but declined to register me as no second dose was available; perhaps an artefact of the software system as much as supply logistics.

VA scheduling and implementation was efficient and trouble free with walk-ins interleaved with scheduled appointments.

 

[bhobba]

Over time it will be impossible to conduct Placebo controlled trials, we will have to rely more on observational studies.

Yes. Challenge trial studies are however another matter - and the UK has flagged they will definitely be looking into that. Unless of course, and this would IMHO a good outcome, everyone gets the vaccine, so no unvaccinated person can be found to participate, even though challenge trials require a much smaller number of people. This will be more 'ethical' if an effective treatment can be found eg the claims for Ivermectin turn out to be valid.

Thanks
Bill

 

[PeroK]

Interestingly, when you look at the video I posted, that carefully goes over the UK data (not just Scotland) what they found is in the first 9 days after vaccination the odds of getting Covid rose 48%. I do not think anybody as yet is 100% sure why (again further research is needed) but the hypothesis is people when vaccinated went whoopee - and stopped taking precautions.

That's interesting. There are, of course, other possible explanations.

First note that as the number of unvaccinated people significantly outnumbers the number vaccinated in a short period, it doesn't take much to generate a 48% increase - although at first this looks fairly significant.

Let's say Scotland vaccinated 30,000 people one day. You would expect about 4 of those per day to test positive subseqently (going by the national figures). It only takes two extra per day (out of 30,000) to push the numbers up by +50%. That increase can be achieved with relatively few people making whoopee.

It's possible that attending the vaccination centre itself was something of a risk. It was in my mind when I went that it was a risk that had to be taken - although it was relatively quiet when I was there.

It strikes me as the sort of thing that would be very hard to get to the bottom of.

 

[bhobba]

It's possible that attending the vaccination centre itself was something of a risk. It was in my mind when I went that it was a risk that had to be taken - although it was relatively quiet when I was there.

Indeed. That is one reason I will be getting mine from my GP. I will be discussing it with him in the next week or two. But everyone in the practice social distances, wears masks, and there is hand sanitiser everywhere plus after each patient the nurse cleans the consultation room with alcohol (at least it smells like it). It will be interesting to see if the doctor gives the Jab or gets one of the practices nurses to do it. When I was young the doctor gave jabs all the time, but for reasons I do not understand they mostly get the nurse to do it now.

Thanks
Bill

 

[Astronuc]

A family friend, who works as a physician's assistant (and who was vaccinated), informed us last night that two vaccinated co-workers have tested positive for COVID-19. One had received the vaccine in January, but now has COVID-19 symptoms, which the person thought was a sinus infection. The vaccine may lessen the severity of the infection, but time will tell how many vaccinated folks respond to the COVID infection.

We also learned that some long haulers respond positively to the vaccines, i.e., they improve over time.

Update: https://www.businessinsider.com/sou...r-moderna-covid-vaccine-study-mutation-2021-3

Claims:

COVID-19 vaccines from Moderna and Pfizer-BioNTech appear significantly less effective against the Coronavirus variant first found in South Africa, a lab study has suggested.

The percentage of protective antibodies that neutralized the variant - called B.1.351, which has been recorded in 20 US states - was 12.4 fold lower for Moderna's COVID-19 shot than against the original coronavirus, and 10.3 fold lower for Pfizer's, the study authors said.

This was a bigger drop than in previous lab studies testing the vaccines against manufactured forms of the variant, they said. For this study, the researchers used real forms of the variant taken from people who had caught the virus.

Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7
https://www.nature.com/articles/s41586-021-03398-2_reference.pdf

As far as I know, both Pfizer and Moderna have expressed concern about the variants and are looking at a third booster shot, perhaps with a tweek related to E484K mutation.

I one has a chance to get the vaccine, do so. I'm eligible as of tomorrow.

 

[Ygggdrasil]

AstraZeneca released the results of its Phase 3 clinical trial for the AZD1222/ChAdOx1 vaccine that it developed with Oxford University. The trial consisted of 32,449 individuals from the US, France, Chile and Peru, 2/3 of whom received the vaccine and 1/3 of whom received a placebo. The vaccine is an adenoviral vector vaccine like the Johnson & Johnson and Russian Sputnik vaccines.

The two-dose vaccine reduced symptomatic disease by 79%, the company said in a press release, and reduced severe Covid-19 and hospitalization by 100%. AstraZeneca said that the vaccine was equally effective in people over 65, where it had 80% efficacy.

Two volunteers in the study received vaccine for every one that received placebo. Across the study, 141 had symptomatic Covid-19 and five, all in the placebo group, had severe disease.

https://www.statnews.com/2021/03/22...s-better-than-expected-efficacy-in-u-s-trial/

Given the recent concern over blood clots from the vaccine in Europe, the company reviewed trial data for thrombosis and found no increased risk of thrombosis. However, the severe thrombosis events reported in Europe were sufficiently rare that they would be unlikely to be detected in a trial with only ~22,000 vaccinated individuals.

Unfortunately, the results have only been disclosed via a press release from the company. The actual data for the trial are not yet available.

AstraZeneca Press release: https://www.astrazeneca.com/media-c...ca-us-vaccine-trial-met-primary-endpoint.html
Popular press coverage: https://www.statnews.com/2021/03/22...s-better-than-expected-efficacy-in-u-s-trial/
Published phase 2 clinical trial results for the vaccine: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32466-1/fulltext

 

[bhobba]

However, the severe thrombosis events reported in Europe were sufficiently rare that they would be unlikely to be detected in a trial with only ~22,000 vaccinated individuals.

I tried to explain this to my sister yesterday and she just kept saying how do you know. I said the UK did not stop their mass vaccination - all she could say - why did the other countries stop. At that point I gave up. But it still had an 'effect' on her - she only wants the vaccine towards the end of the rollout in Aus now. As far as I know no such 'events' have occurred in the UK where they have vaccinated 28 million people, most with the Oxford vaccine. So it must be very rare.

Thanks
Bill

 

[PeroK]

I tried to explain this to my sister yesterday and she just kept saying how do you know. I said the UK did not stop their mass vaccination - all she could say - why did the other countries stop?

Why did they start again? The EU's actions logically ought to give more confidence. One could argue that the UK might have ignored risks to get the vaccinations going quickly. Whereas, the EU's actions suggest that if there were a risk with the vaccines they would stop.

If there were a serious, known risk with the AZ vaccine, the EU would not have started using it again.

 

[Ygggdrasil]

A safety board overseeing AstraZeneca's COVID-19 vaccine trial is raising concerns about the company's data. In an unusual post-midnight statement, the National Institute of Allergy and Infectious Diseases said the Data and Safety Monitoring Board, which monitors the trial, is concerned "outdated information" may have been included in the trial results.

If the pharmaceutical company did include outdated information from that trial, that could provide an "incomplete view of the efficacy data," the NIAID said.

The DSMB, an independent group within the agency responsible for reviewing clinical studies, also notified other federal health agencies and AstraZeneca directly of its concerns.

Later Tuesday, AstraZeneca released a statement saying that its interim analysis was based on data with a "cut off" of Feb. 17 and that it had "reviewed the preliminary assessment of the primary analysis and the results were consistent with the interim analysis." The company said it expected to release results of its primary analysis within 48 hours.

https://www.npr.org/2021/03/23/9802...vaccine-trial-data-questioned-by-safety-board

NIAID press release: https://www.nih.gov/news-events/news-releases/niaid-statement-astrazeneca-vaccine
AstraZeneca press release: https://www.astrazeneca.com/content...niaid-on-azd1222-us-phase-iii-trial-data.html

 

[Astronuc]

In 2020, Covid-19 vaccines shattered previous speed records, going from development to FDA approval in less than one year. Before that, the fastest vaccine to receive FDA approval in the US was the mumps vaccine, which took four years. So how did they do it? Vaccines including those from Pfizer/BioNTech, Moderna, Johnson & Johnson, and AstraZeneca used new methods that give genetic instructions directly to human cells.

https://www.vox.com/2021/2/2/22262226/covid-19-vaccines-mrna-adenovirus

 

[Ygggdrasil]

AstraZeneca's latest data analysis affirms effectiveness of its COVID-19 vaccine and is roughly in line with the results released Monday.

The latest analysis finds the vaccine to be 76% effective against symptomatic COVID-19 and 100% effective against severe or critical disease and hospitalization. These results are very close to the results that came out at the beginning of the week: 79% vaccine efficacy at preventing symptomatic COVID-19 and 100% effective against severe or critical disease and hospitalization.

An independent monitoring board raised questions about the company's release Monday — a day after the company announced that the higher efficacy rate -- saying it didn't include more up-to-date cases that were available.

https://www.npr.org/2021/03/24/9810...eport-supports-effectiveness-of-covid-vaccine

AstraZeneca press release: https://www.astrazeneca.com/content...ry-analysis-confirms-safety-and-efficacy.html

The 76% effectiveness presented by the company still seems slightly higher than effectiveness estimates quoted from the Data Safety and monitoring Board who also reviewed the data and saw 69-75% effectiveness.

In a memo sent to company and government officials, obtained by The Washington Post, experts who have been overseeing the vaccine trial expressed concern and disappointment that the drugmaker had presented “outdated and potentially misleading” data on its Coronavirus vaccine, making the shots appear more effective than shown by fuller data.

On Monday, AstraZeneca and academic scientists trumpeted a vaccine that was 79 percent effective in its large U.S. clinical trial. That news release triggered concern among independent monitors who had seen more recent data, because when an additional month was taken into account, the effectiveness ranged from 69 to 75 percent.

The letter came from 11 leading statisticians, infectious-disease physicians and ethics experts appointed by the National Institutes of Health to review trial data for all the major Coronavirus vaccines supported by the federal government.

https://www.washingtonpost.com/worl...931d34-8bc3-11eb-a33e-da28941cb9ac_story.html

 

[Klystron]

After being too young by one year for the initial public vaccine program in southern Nevada USA, I received the Pfizer vaccine first dose this week at our local veteran's hospital after minimum age reduction from 70 to 65 years old. Second dose scheduled in 21 days.
{snip}

Received my second dose of Pfizer vaccine 24 March from the VA hospital. I felt fine afterward, only tired from the long drive. Normal~8 hour sleep. No unusual pain. I felt tired and groggy for a week after first dose.

I felt exceptionally good the following day. Cleaned home including vacuuming and steam cleaning new floors installed after water leak repaired; activity that would normally exhaust me. Attended two hour late virtual meeting via Zoom with no loss of attention. Slept ~7 hours.

Attended physical therapy today (day 3). Felt energetic. Completed entire exercise schedule followed by weekly grocery shopping. Noticed no ill effects from vaccine; rather the opposite. Either I am experiencing a profound placebo impact, or the second dose has made me feel much better than before.

 

[bhobba]

Why did they start again? The EU's actions logically ought to give more confidence.

Of course. But, especially with regard to Covid, people's logic sometimes seems 'compromised'. I am starting to reach the conclusion best not to discuss Covid except here and with my doctors. Not there yet - but it may come. Personally the huge number of Oxford vaccines given showed if it was an issue it was very very rare and there was no need to stop. Just my view - there is public perception to consider, which I think is why it really was temporarily halted to investigate the issue. But I am not the one in charge of these things who must take many factors including public confidence into consideration.

Interesting development with the Oxford vaccine in the US I will do a separate post about.

Thanks
Bill

 

[bhobba]

The 76% effectiveness presented by the company still seems slightly higher than effectiveness estimates quoted from the Data Safety and monitoring Board who also reviewed the data and saw 69-75% effectiveness.

You stole my thunder. . I was going to do a separate post about it:

It will almost certainly eventually be approved in the US, and since the US has 300 million doses on order, will help greatly with the mass vaccination there. I have noticed AstraZenica tends to 'hype' the Oxford vaccine in their press releases which means one really must read the preprint to get the full picture. Not a good way of doing things - it just creates 'doubt' - the last thing you want in a pandemic - and slows down approvals.

The trial was with the second dose after 4 weeks. But we know, from UK data where nearly 30 million doses have been given (total vaccinations - predominantly Oxford but some Pfizer and recently Modernia) it has a 73% effectiveness after 35 weeks with just one dose, but only 80% effective in preventing hospitalisations. When given the second dose, which has not been done in the UK yet, so no large scale data is available, trials showed it is 100% effective in preventing hospitalisations. But if you wait 12 weeks there is evidence the effectiveness against getting Covid rises to 83%, with still 100% effectiveness in preventing hospitalizations. To wait to give the second dose at 12 weeks or 4 weeks is the question. Decisions, decisions. Here in Aus they will be using 12 weeks. I suspect because we just a few hours ago detected our first case of community transmission in a long time:
https://www.sbs.com.au/news/new-bri...was-infectious-in-community-for-almost-a-week

This locking down of disability services causes people (including me) quite a bit of difficulty - but they seem able to get by. People generally are helpful. In my case, luckily, before the lockdown my house was cleaned yesterday.

Thanks
Bill

 

[Borg]

I have been checking out the vaccination rates in Fairfax County, VA for the last three weeks and have watched it climb from 21K doses received per week, to 32 last week, to over 43K this week. Meanwhile, their waitlist has been cut in half during that same time.

 

[Astronuc]

AstraZeneca and rare thrombosis
https://www.usatoday.com/story/news...ood-clots-not-definitively-linked/4721828001/

In early March, reports of cases involving blood clots, abnormal bleeding and low blood platelets – a few fatal – led many European countries to temporarily suspend AstraZeneca-Oxford's COVID-19 vaccine, which is not available in the U.S. The European Union's drug regulatory agency, European Medicines Agency, later said the vaccine did not increase the overall incidence of blood clots and that the benefits of using it outweighed the possible risks. Vaccines are not known to cause blood clots although there have been cases of immune thrombocytopenia, a rare condition marked by low platelets, following vaccination with Moderna's and Pfizer's COVID-19 vaccines.

The article did not provide a definitive statement on the cause of clotting with vaccines, only that rare cases have been reported.

https://www.dw.com/en/astrazeneca-german-team-discovers-thrombosis-trigger/a-56925550
https://www.dw.com/en/astrazeneca-whats-the-deal-with-thrombosis/a-56901525

Forbes is the only news source I found that states the cause and treatment.
https://www.forbes.com/sites/rachel...azenecas-vaccine-is-causing-rare-blood-clots/

Scientists at Greifswald University Hospital said in a statement Friday that in rare instances, the vaccine has created an antibody that triggered the formation of blood clots in the brain.

The findings confirm those from an independent team in Norway earlier this week.

Isolating the cause has allowed scientists to identify how to treat patients who have developed the blot clots, by giving them intravenous immunoglobulin, which targets the antibody, and blood thinners.

 

[Ygggdrasil]

New data from a phase 3 clinical trial of the Pfizer-BioNTech vaccine in adolescents (aged 12-16) suggests that the vaccine is effective in that age group:

The Phase 3 trial enrolled 2,260 adolescents who were randomly assigned to receive two doses of the vaccine or placebo. The main measure of the vaccine’s efficacy was whether a subset of subjects developed antibodies at the same level seen in older adolescents and adults. The antibody levels, expressed as SARS-CoV-2 neutralizing geometric mean titers, were 1,239.5, compared to geometric mean titers of 705.1 in subjects between the ages of 16 and 25 in previous studies. Those levels are considered non-inferior to one another.

But the vaccine also prevented symptomatic Covid-19 infection. There were 18 cases of Covid-19 among patients who received placebo and none in those who received the vaccine, the companies said.

https://www.statnews.com/2021/03/31/pfizer-covid19-vaccine-adolescents-data/

Pfizer press release: https://www.pfizer.com/news/press-r...ech-announce-positive-topline-results-pivotal

In the US, the FDA's emergency use authorization allows use of the vaccine only in those age 16 and over. These data could lead the FDA to expand the EUA to allow use of the vaccine in those age 12 and over. There are also trials underway testing the vaccine in children ages 6 mo - 11 years.

 

[Laroxe]

AstraZeneca and rare thrombosis
https://www.usatoday.com/story/news...ood-clots-not-definitively-linked/4721828001/
The article did not provide a definitive statement on the cause of clotting with vaccines, only that rare cases have been reported.

https://www.dw.com/en/astrazeneca-german-team-discovers-thrombosis-trigger/a-56925550
https://www.dw.com/en/astrazeneca-whats-the-deal-with-thrombosis/a-56901525

Forbes is the only news source I found that states the cause and treatment.
https://www.forbes.com/sites/rachel...azenecas-vaccine-is-causing-rare-blood-clots/

This addresses the possible mechanisms in more detail and identifies other diseases and sometimes their vaccines that are associated with coagulopathies. In Covid 19 infection, it is surprisingly common but is strongly associated with the severity of the disease, there are also quite a range of issues that are known to increase risk though these shouldn't play a part post vaccination. Its interesting that the group identified as most at risk is not concordant with the disease risk, this suggests a rather different sort of pathology. The first link describes the possible pathology in the actual disease.

The second link is more specific to the current situation and offers some comparisons between vaccines.
The fact that this risk has been identified as being associated with Covid 19 does mean that there is much more screening being used and that may account for some of the differences in the numbers recorded. The fact that these adverse events seem more common in young women and typically within 14 days of vaccination seems to support the idea that it is an autoimmune response.

With these details in mind and in view of the recommendations of various scientific advisory groups, there is no doubt that this is an issue that needs to be closely monitored. However being a devout cynic I thinks its impossible to make much sense of the various responses to restrict the vaccine yet again, without putting the situation in context. Politicians across Europe have been engaged in promoting misinformation in relation to the AZ vaccine as part of their dispute with the company and by proxy the UK. Despite their complaints their own efforts have lead to a situation in which around a third of the doses delivered have yet to be given and they are threatening the whole of the global supply of vaccines.
The data being used is derived from the various passive reporting systems used to monitor adverse events, the same data that anti vax groups misrepresent to promote their views.

In reality, thromboembolic events have been reported as potential adverse events for AZ, Pfizer and Moderna vaccines at similar rates. Reporting systems in the US which doesn't use the AZ vaccine have recorded some 150 such events. The yellow card system in the UK suggests that in the adverse event reports for the AZ and Pfizer vaccines the numbers are very similar. In the UK where large numbers of vaccinations have been carried out there is no indication that blood clots are occurring more frequently, in fact there appears to be a negative correlation. This is something various groups have identified in their risk assessments.

The final link is to the Canadian advisory body which has said that Overall, https://www.canada.ca/en/health-canada/news/2021/03/health-canada-confirms-that-the-benefits-of-the-astrazeneca-covid-19-vaccine-continue-to-outweigh-the-risks-for-use-in-canada.html that the benefits of the AstraZeneca COVID-19 vaccine continue to outweigh the risks, before the government introduced more control over its use. These restrictions are being introduced as case numbers and deaths from the disease are increasing and dissent in Europe in particular, growing.

https://thorax.bmj.com/content/76/4/412

https://www.bmj.com/content/372/bmj.n699

https://www.cbc.ca/news/health/faq-covid-astrazeneca-vaccine-blood-clots-1.5959447

 

[Astronuc]

Over 100 Washingtonians became ill with Coronavirus despite vaccinations, DOH says
https://keprtv.com/amp/news/local/o...got-coronavirus-despite-vaccinations-doh-says

I heard 102 persons who had been fully vaccinated contracted the SARS-Cov2 and developed COVID-19. Of those, 8 are hospitalized. The details are not yet available, but hopefully, we'll find out the vaccine, the demographics and how severe the illness. Nevertheless, everyone should continue to wear a mask and socially distance to the extent possible in public.

Out of one million fully vaccinated individuals in Washington state, epidemiologists report evidence of 102 breakthrough cases since February 1, 2021, which represents .01 percent of vaccinated people in Washington. Breakthrough cases have been identified in 18 counties. The majority of those in Washington state with confirmed vaccine breakthrough experienced only mild symptoms, if any. However, since February 1, eight people with vaccine breakthrough have been hospitalized. DOH is investigating two potential vaccine breakthrough cases where the patients died. Both patients were more than 80 years old and suffered underlying health issues. Further investigation will help to identify patterns among people who have COVID-19 after vaccination, such as if a virus variant may have caused the infection.

 

[Astronuc]

Johnson & Johnson COVID-19 vaccine batch fails quality check
https://apnews.com/article/health-c...irus-vaccine-05ac1d5c84c2945d48fd179c2733e84e

Ouch!

A vaccine ingredient made by Emergent BioSolutions — one of about 10 companies that Johnson & Johnson is using to speed up manufacturing of its recently approved vaccine — did not meet quality standards, J&J said.

J&J said the Emergent BioSolutions factory involved had not yet been approved by the U.S. Food and Drug Administration to make part of the vaccine. Emergent declined to comment.

 

[Ygggdrasil]

Here's a nice article describing efforts to develop a universal Coronavirus vaccine that would protect against multiple variants of the virus and potentially even new zoonotic coronaviruses that could emerge in the future:

Instead of using the spike protein of SARS-CoV-2, which is prone to mutations, as the key target for Coronavirus vaccines, researchers are assessing other parts of the virus that are known to be more stable.

For example, scientists at the University of Nottingham in the UK are working alongside pharmaceutical company Scancell and Nottingham Trent University to test its COVID-19 vaccine candidate, SN14, which targets both the spike protein as well as the nucleocapsid, or N-protein. By targeting this additional viral structure, which is far less likely to mutate, the vaccine if found safe and effective could work to protect people against COVID-19 irrespective of any mutations to the spike protein and, in theory, could work across other coronaviruses.

Elsewhere, CalTech in the US have engineered a prototype all-in-one vaccine using a nanoparticle to hold fragments of the spike protein from multiple known coronaviruses. The innovative platform was found to trigger the production of antibodies against several coronaviruses in preclinical testing last month. Importantly, it not only protected against the Coronavirus antigens in the vaccine but also against related strains, suggesting an immune response had recognised common features across coronaviruses. This approach could therefore provide protection against newly emerging coronaviruses in the future.

Another approach, suggested in a recent Nature commentary, could be to look at whether broadly neutralising antibodies, known to work against multiple HIV strains, also exist for coronaviruses.

https://www.gavi.org/vaccineswork/going-universal-search-all-one-coronavirus-vaccine

These vaccines are still in the early stages of research, so they're unlikely to help with the current pandemic. However, given that we've seen three new coronaviruses emerge to cause outbreaks in people in the past two decades (SARS in 2002, MERS in 2012 and SARS-CoV-2 in 2019), vaccines and therapeutics that act broadly against multiple different strains of coronaviruses are definitely something that would be of great use in preventing future pandemics.

 

[Rive]

These vaccines are still in the early stages of research, so they're unlikely to help with the current pandemic.

I wonder if those attempts would work with the spike being front, in the way...


By the way, are there any news about vaccine modifications against the new mutations? Or maybe about polyvalent vaccines?
Even if it's early right now, it would worth to know if the existing vaccines can be safely modified this way.
Some proactivity instead of just passively reacting to events...

 

[Ygggdrasil]

I wonder if those attempts would work with the spike being front, in the way...By the way, are there any news about vaccine modifications against the new mutations? Or maybe about polyvalent vaccines?
Even if it's early right now, it would worth to know if the existing vaccines can be safely modified this way.
Some proactivity instead of just passively reacting to events...

Because of the nature of the mRNA vaccines, it is extremely quick to design new vaccine candidates once we have genetic sequence information for the virus. For example, Moderna designed its mRNA vaccine candidate just 2 days after the genetic sequence of the SARS-CoV-2 virus was made publicly available.

Both Pfizer and Moderna have initiated clinical trials to test booster shots of their vaccines aimed at providing immunity to some of the new strains that seem to evade antibody-based immunity (e.g. the B.1.351 variant). The FDA has said that these vaccines would undergo a review process similar to those given to annual flu vaccines such that they could be approved for use in the fall, if all the data look good.

https://www.nih.gov/news-events/new...ating-moderna-covid-19-variant-vaccine-begins
https://www.pfizer.com/news/press-r...iontech-initiate-study-part-broad-development

It is likely that the other vaccine manufacturers have begun testing vaccines against some of the new variants as well. These companies are definitely being proactive in trying to keep pace with the evolution of the virus (indeed, proactive R&D done in the previous decade by companies like Moderna through efforts like CEPI that fund epidemic preparedness are one reason why vaccines were able to be developed and approved so quickly).

 

[Mary Conrads Sanburn]

NEWS RELEASE 16-APR-2021

Study shows past COVID-19 infection doesn't fully protect young people against reinfection

THE MOUNT SINAI HOSPITAL / MOUNT SINAI SCHOOL OF MEDICINE

Although antibodies induced by SARS-CoV-2 infection are largely protective, they do not completely protect against reinfection in young people, as evidenced through a longitudinal, prospective study of more than 3,000 young, healthy members of the US Marines Corps conducted by researchers at the Icahn School of Medicine at Mount Sinai and the Naval Medical Research Center, published April 15 in The Lancet Respiratory Medicine.

"Our findings indicate that reinfection by SARS-CoV-2 in health young adults is common" says Stuart Sealfon, MD, the Sara B. and Seth M. Glickenhaus Professor of Neurology at the Icahn School of Medicine at Mount Sinai and senior author of the paper. "Despite a prior COVID-19 infection, young people can catch the virus again and may still transmit it to others. This is an important point to know and remember as vaccine rollouts continue. Young people should get the vaccine whenever possible, since vaccination is necessary to boost immune responses, prevent reinfection, and reduce transmission."
[ . . . ]
###

This work was supported by the Defense Health Agency through the Naval Medical Research Center and the Defense Advanced Research Projects Agency.
https://www.eurekalert.org/pub_releases/2021-04/tmsh-ssp041621.php