Categories
AstraZeneca Moderna Pfizer Vaccine

Delayed Second Dose

People who got their first Pfizer and Moderna vaccine are expected to get their second dose 21 and 28 days later. The UK just approved AstraZeneca, of which people got their second dose 28 days later in clinical trials.

However, yesterday the UK made waves by announcing that they are prioritizing first doses. In other words, people won’t get their second dose of AstraZeneca or Pfizer until up to 3 months after their first dose. This is a bold approach… give as many people their first dose as fast as possible (rather than providing two doses to fewer people). Some places in Canada have been doing this and Belgium is considering it too.

Does timing of the second dose matter? This question has sparked quite the scientific debate.

On one hand, this could be a brilliant decision. Especially in a country where transmission is out of control due to a new variant. This decision could result in less deaths. Biologically (and historically) getting a vaccine a day or week late doesn’t matter much. The immune system usually doesn’t need that much precision. And sometimes the longer between doses, the better efficacy. But 3 months later? Not sure.

On the other hand, this could be a regrettable decision. During a pandemic with significant transmission of a disease, getting a vaccine exactly as it had been studied is important because: 1) People are much better off being fully protected. For example, in the Pfizer trial, the level of protection increased dramatically (52% to 95%) after the second dose; 2) The second dose typically provides longer-lasting immunity than the single dose; and, 3) Dr. Paul Bieniasz (Rockefeller biologist that studies the evaluation of viruses) said that this could cause partial antibody resistance among a population that is semi-immunized. “If I were designing a vaccine-resistant [COVID19 virus], I’d do what they are doing in the UK”. This is an experiment in viral evolution during the middle of a pandemic.

So, in short, the vaccine studies weren’t designed for a delayed dose, so we really don’t know the implications. AstraZeneca also hasn’t released their full data report, even though the regulators had a copy this week. So we can’t really parse out the data to make more accurate hypotheses. Word on the street is that some people had their second dose in the AstraZeneca trial much later than 28 days, but I have yet to see that data.

We’ll just have to see how this goes…

Love, YLE

Categories
Side Effects Vaccine

Adverse Events Update 12/28/2020

As of December 28th, 2.13 million Americans received their first dose of the COVID19 vaccine; 11.45 million doses have been shipped to US providers.

Among the 2.13 million Americans, there have been only 353 people (that’s 0.017%) who reported an adverse event to the CDC.

Among the 353 people that experienced adverse events…

• The vast majority have mirrored mild-to-moderate reactions in clinical trials (see first figure; these are not mutually exclusive)

• Only 8 of these events are classified as “serious” (see second figure)

• Of the 8, 4 people were hospitalized

• 0 have resulted in death

• 73% of the events occurred in young adults aged 18-49

• 2 events were severe allergic reactions (anaphylactic shock)

Adverse events for COVID19 vaccinations (and all vaccinations by the way) are tracked and reported within the CDC Vaccine Adverse Event Reporting System (VAERS). This information is ALL public and you can play around with tables and charts here: https://vaers.hhs.gov/data.html. This system even allows you to read the physician notes on what exactly happened with each patient. It’s incredibly transparent.

Keep in mind that not every system is perfect; there are some limitations to VAERS. Healthcare providers, vaccine manufacturers, and the public can submit reports to VAERS. While very important in monitoring vaccine safety, VAERS reports alone cannot be used to determine if a vaccine caused or contributed to an adverse event or illness. The reports may contain information that is incomplete, inaccurate, coincidental, or unverifiable. Most reports to VAERS are voluntary, which means they are subject to biases. This creates specific limitations on how the data can be used scientifically. Data from VAERS reports should always be interpreted with these limitations in mind.

Love, YLE

Data Source: https://vaers.hhs.gov/data.html

Graphs: By yours truly

Categories
Texas update Vaccine

Phase 1B opened in Texas

Texans….Phase 1B has opened.

So, if you’re in this category, you can now get the COVID-19 vaccine (depending on local availability):

• People 65 years of age and older

• People 16 years of age and older with at least one chronic medical condition, such as but not limited to:

• Cancer• Chronic kidney disease• COPD (chronic obstructive pulmonary disease)• Heart conditions, such as heart failure, coronary artery disease or cardiomyopathies• Solid organ transplantation• Obesity and severe obesity (body mass index of 30 kg/m2 or higher)• Pregnancy• Sickle cell disease• Type 2 diabetes mellitus

Here is the map of vaccine providers: https://txdshs.maps.arcgis.com/…/webappvi…/index.html…

This week 380,000 doses (175,100 Moderna and 81,900 Pfizer) were sent to Texas providers in 199 counties. This obviously doesn’t cover every Texan in Phase 1B. Be patient. Some providers may not have vaccines available yet. Vaccine supply is limited but providers receive more vaccines each week.

Update: As of 4pm today, 204,463 Texans have gotten their first dose!

Love, YLE

For more, check out the DSHS website here: https://www.dshs.texas.gov/coron…/immunize/vaccine.aspx…

Categories
Novavax Vaccine

Novavax Vaccine

Alright, now on to Novavax…

Novavax is a small company based in Maryland and has never brought a vaccine to market. This company has a fascinating rollercoaster history; I highly recommend googling over coffee.

Novavax is using a different vaccine formula than Moderna, Pfizer, AstraZeneca, and Janssen. The Novavax vaccine contains a cornavirus protein that prompts the immune system. Scientists combined this protein with an immune-boosting compound derived from the soapbark tree. They tried doing it without this adjuvant but the vaccine didn’t work as well. Anyways, this type of vaccine has a much longer track record than the newer approaches.

The exciting (and innovative) aspect of this vaccine is that Novavax found a way to make this vaccine in moth cells (rather than mammal cells). The moth cells basically become little factories that pump out coronavirus proteins. This allows Novavax to manufacture the vaccine much quicker than others, which is obviously a big plus in the time sensitive pandemic.

The Novavax vaccine has gone through animal and small human trials so far. In animal studies, the Novavax vaccine provided stronger protection for monkeys than have other coronavirus vaccines. This isn’t surprising though, as other scientists predicted (and published) that the protein-based vaccine would be highly effective.

In August, Novavax published promising preliminary results: 56 volunteers produced a high level of antibodies against the virus without any dangerous side effects. Then, in September, Novavax started human Phase III trials in Britain among 15,000 people. The results from this trial should be ready early 2021. Novavax said that over 25% of participants in this trial are over the age of 65, with a lot of participants also having underlying medical conditions.

Yesterday, Phase III started in the US and Mexico. They plan on enrolling 30,000 people at 115 sites. It was supposed to start earlier (October), but Novavax ran into commercial manufacturing scale-up problems.

Love, YLE

PS After seeing some concerning comments yesterday, I want to make it very clear that I have no conflicts of interest with any of these vaccine sponsors. Although it would be nice to be paid for this 😉 (half joking). I’m cheering for all the vaccines to make it to the finish line, but I think education and transparency is equally as important for the community.

Prediction: https://jvi.asm.org/content/94/17/e01083-20

Early results: https://www.nejm.org/doi/full/10.1056/NEJMoa2026920

Novavax History: https://www.google.com/…/coronavirus-vaccine-novavax…

Categories
AstraZeneca Vaccine

AstraZeneca Update

Alright, next up AstraZeneca…

AstraZeneca has four ongoing trials. Late in November, they reported interim results from two of the four trials (UK and Brazil) with approximately 4 months of follow-up data among 11,636 people. AstraZeneca initially reported that the vaccine had 70% efficacy.

Shortly after the report was released, a big mistake was revealed. Researchers in the UK had been meaning to give volunteers the initial dose at full strength, but they made a miscalculation and accidentally gave it at half strength. About 3,000 participants were given the half dose and then a full dose four weeks later; nearly 9,000 volunteer were given two full doses four weeks apart.

This may have been a lucky mistake. The half-dose regimen had 90% efficacy; the full-dose regimen had 62% efficacy.

No one knows why the half dose regimen worked better. There are two hypotheses: 1) The lower first dose did a better job of mimicking the experience of an infection, promoting a stronger immune response; 2) It isn’t truly better. Participants who received the half-dose regimen had been exclusively <55 years old. It’s possible that volunteers who got the half doses are different (ie healthy) compared to those who got the full dose regimens, making it seem like efficacy is higher. Since age is the biggest risk factor for getting seriously ill with COVID19, this is an extremely important consideration.

This error and a series of other irregularities are causing scientists to lose confidence in the reliability of the results. It’s not clear, at least to me, whether AstraZeneca is making rookie mistakes or if they are blatantly nontransparent. For example,

1. They initially pooled data and reported 70% efficacy. When, in fact, efficacy was 62% and 90%. This was just wrong.

2. They also initially pooled Brazil and UK data even though the trials were designed differently (ie different dose intervals). Pooling different clinical trials is a break from standard practice.

3. They halted the trial because of an unexplained illness. This IS completely normal. However, AstraZeneca didn’t promptly announce the decision publicly. Instead, they provided details about the nature of the illness on a private conference call with investors hosted by the investment bank J.P. Morgan. This is just…weird?

The US trial is still underway and results should come in late January. There is no indication the the US has made the half dose error, so we should get some solid data. And, although the efficacy may be lower than other vaccines, FDA is requiring 50% efficacy benchmark, so it could pass. I’m looking forward to the FDA external advisory board meeting, as it should be a VERY interesting discussion about AstraZeneca’s errors and whether they cloud confidence.

The UK external advisory board is meeting TODAY to discuss the AstraZeneca vaccine and whether to grant emergency approval. This should also be interesting; stay tuned.

In the meantime, AstraZeneca has said it is considering a new global trial based on the half dose first regimen.

Love, YLE

AstraZeneca published results:https://www.thelancet.com/…/PIIS0140-6736(20…/fulltext

Categories
Vaccine

Vaccine Update

We cannot vaccinate fast enough. To our advantage, though, many more vaccines are coming down the pipeline. Janssen and AstraZeneca will likely be available next, followed by Novavax which is about to start its research trial.

If you’re like me, these are starting to get difficult to keep track of, so I started a Table for myself. It may (or may not) be helpful for you too. It’s not very pretty, but I’m a researcher not a graphic designer 🙂

Over the next few days, I’ll give you updates on each one of these. Today… Janssen.

– Janssen is the pharmaceutical arm of Johnson & Johnson (J&J) company, which resides in Belgium

-Currently in Phase 3 testing a single dose. The sponsor has given this study a name: ENSEMBLE

-Trial is only among adults 18+ with controlled comorbidities. 45,000 people are currently enrolled

-This is an adenovirus-based vaccine; basically a small piece of genetic material from the virus is used to trigger an immune response. J&J has been working on this biotechnology for decades. They just had an Ebola vaccine approved using this same idea. They are currently in trials for HIV and Zika vaccines too. The AstraZeneca also uses adenovirus technology 

-Trials were temporarily delayed for an unexplained illness on October 12, but has since determined the event was not related to the vaccine and the trial was safe to resume.

-This vaccine is more rugged than Moderna or Pfizer. DNA is not as fragile as RNA. And this vaccine has a tough coat protecting the pieces. As a result, storage is much easier for the J&J vaccine 

-J&J should have safety and efficacy data by end of January. And expected to seek emergency use authorization by early February

-J&J also announced a separate double dose study (ENSEMBLE2)

Love, YLE

Data Source: https://www.jnj.com/johnson-johnson-posts-interim-results-from-phase-1-2a-clinical-trial-of-its-janssen-covid-19-vaccine-candidate

Categories
Variant

Update on the UK variant…

The UK COVID19 variant (called VOC 202012/01) has 17 mutations, among which eight are located in the spike protein (the key which unlocks our cells for infection). At least three mutations have the potential to change the game.

A few days ago, scientists from the Center for Mathematical Modeling of Infectious Diseases came out with the first (and only) study on the new UK variant. The scientists were able to get this out quick because this study is considered a “social” epidemiological study. In short, they used data from hospitals, seroprevalence, and mobile phones to model mathematical equations.

They found that the new variant is spreading faster. In fact, it’s 56% more transmissible than previous variants. They were able to use the equations to know that the increase is NOT due to increased social interactions. This suggests that, wherever this variant is, there will be an onslaught of cases. The epidemiological curve in Wales is something we can expect. The good news is that the variant doesn’t lead to a higher rate of severe disease (ie symptoms or death). In other words, if you get infected by this variant, the likelihood of ending up in the hospital or dying is the same as other variants.

The scientists were very clear that current public health measures won’t stop its spread. The R(0) is too high. They suggested that schools need to be closed until February. Especially since it seems that this new variant is highly transmissible among kids (this is where the hot spots of the new variant seem to be coming from). Also, they called for more urgent vaccination campaigns. We aren’t vaccinating quick enough.

We aren’t sure if this new variant is in the United States. However, we would be surprised if it wasn’t, considering the incredible global reach of COVID19. Anything we do now (like cancelling flights) is likely way too late.

This study starts painting a very important picture of the new variant. We are still waiting on “biological” studies to point us to the exact mutation that’s causing this, so we can learn more. In the meantime, stay vigilant and get your vaccine.

Love, YLE

Abstract: https://cmmid.github.io/topics/covid19/uk-novel-variant.html

Study: https://cmmid.github.io/…/2020_12_23_Transmissibility…

Categories
Variant

New COVID19 variant/strain in UK

Yes, there is another variant in the UK that MAY be increasing transmissibility. Cases are increasing at exponential rate in Wales. But there are a few things to keep in mind…

To mutate and change is what viruses do. Most of the time it’s a meaningless tweak. Sometimes the virus gets worse at infecting us and the new variant just dies out.

Sometimes the virus just gets lucky, in that a new variant hits the right people at the right time. This happened in Spain during the summer. Headlines called it the the “Spanish strain”, but the exponential cases was explained by simply people catching it on vacation and bringing it home. It wasn’t due to the new variant. It’s important to keep in mind that the virus spreads with political and social contexts in the background. The UK may be placing the blame of new Christmas shutdowns on science, rather than taking the blame of soaring cases due to lax policies.

Sometimes, though, viruses do find a new winning formula. But, we honestly don’t have the data yet to know the full picture. The World Health Organization is working on it. It will take laboratory experiments to figure out if this variant really is a better spreader than all the others.

Will this impact the effectiveness of the vaccine? Probably not. It takes a collection of mutations to impact vaccines. Vaccines are made with mutations in mind. This UK variant has a mutation on the spike protein of the virus. It’s not the first time we’ve seen a mutation on the spike protein. This gains the attention of scientists, though, because the spike is the virus’s key to unlock the door into our cells. Any changes made to that key can make it easier for the virus to get inside. This mutation is certainly something to keep an eye on.

As one professor (McNally) said: “We know there’s a variant, we know nothing about what that means biologically…It is far too early to make any inference on how important this may or may not be.”

So, in the meantime, everyone take a big, deep breath. Including those in charge of news headlines. Keep doing what you’re doing. This has no implications (yet) on how we should change behavior. Keep washing those hands, keeping your distance, and wearing masks.

Love, YLE

Categories
Behaviors Children Daycare Social Distancing

COVID19 infections among kids…

Kids (<18 years) make up of 10% of COVID19 infections in the United States. Because of that, it’s taken a bit more time to have enough infected kids for meaningful analyses (compared to adults). The CDC published an important study Tuesday assessing school, community, and close contact exposures associated with child and adolescent COVID-19 infection.


The study took place from Sept to Nov 2020 in Mississippi. 397 parents of children who recently had a COVID19 test completed a phone survey. They answered questions about symptoms, close contact with a person with known COVID-19, school or child care attendance, and family or community exposures ≤14 days before the COVID test. Then, scientists compared the answers across kids with a COVID19- test to kids with a COVID19+ test. There were a couple things they found…

COVID+ kids were MORE likely to have…

  • Had close contact with a person with known COVID-19. And, this close contact was more likely to be a family member than someone at school
  • Attended gatherings with people outside their home, including social gatherings (weddings, parties, funerals, birthday parties), playdates, or to have had visitors at home

COVID+ kids were LESS likely to have…

  • Consistent mask use by students and staff members inside school or child care facilities

Interestingly, there were essentially no difference between COVID+ and kids going to…

  • Sports events or concerts (18% COVID+ vs. 20% COVID- kids)
  • In-person school or child care (62% COVID+ vs. 68% COVID-)
  • Religious services (13% COVID+ vs. 18% COVID-)
  • Restaurants (20% COVID+ vs. 16% COVID-)
  • Travel with others (5% COVID+ vs. 3% COVID-)
  • Household member working in health care (24% COVID+ vs. 21% COVID-)


Before I get the comments, here are a few important notes…

1. This doesn’t mean, for example, you have carte blanche to go to indoor restaurants. This is a study of kids. This does not mean you, as a parent, won’t get it or spread it

2. No, there is no data on teachers or staff. Yes, that would be a needed analysis. I’m sure it’s coming.

3. Yes, masks work. This study showed that adults wearing masks helps kids, especially within schools and child care center. If you need more evidence, check out my previous post (https://yourlocalepidemiologist.com/masks-work/)

4. Opening schools is a bit more complex than kids getting infected. Kids are less likely to get sick (and not go get a test), but they harbor the disease and have the potential to spread it to others. Unfortunately, we still don’t know the rate of transmission from kids to adults.


Finally, I would like to take a moment to recognize how quickly and hard these scientists had to have worked to get this information out to the public. Data collection ended November 5, 2020. That means, within a MONTH, they cleaned the data, analyzed the data, came to meaningful conclusions, wrote up the science, sent it up the CDC ranks for approval, responded to feedback, and submitted for publishing. For the record, this typically takes 1-2 YEARS. Absolutely incredible.


Love, YLE

Data Source: Hobbs CV, Martin LM, Kim SS, et al. Factors Associated with Positive SARS-CoV-2 Test Results in Outpatient Health Facilities and Emergency Departments Among Children and Adolescents Aged <18 Years — Mississippi, September–November 2020. MMWR Morb Mortal Wkly Rep 2020;69:1925-1929. DOI: http://dx.doi.org/10.15585/mmwr.mm6950e3

Categories
Vaccine

Moderna second half report…

Allergic reactions came up again. Moderna provided some important context. The company has 12 other mRNA vaccine trials (for other viruses), totaling 17,000 participants. Among these trials, there was only 1 person with a severe allergic reaction (she had a soy allergy). BUT this allergic reaction was 2 months after vaccination, so not related to the vaccine. This is important to know because all of Moderna’s trials use the same fat bubble (the thing that causes side effects). Moderna’s fat bubble (I’ve posted about this before) is different than Pfizer’s fat bubble; Moderna’s is more stable (hence why it doesn’t have to be refrigerated at such drastic temperatures compared to Pfizer). Because of that, we should not (and cannot) pool severe reactions, like allergies, from the two trials. We have to treat them separately, even though they are using the same biotechnology concept.

Moderna then dropped some exciting news that they have a LOT more data coming soon. For this emergency authorization, they needed 196 cases of COVID19 to test efficacy. But, they already have 450 more cases. Unfortunately, 1 person in the placebo group has died of COVID19.

Then there was discussion about one unexpected side effect…facial swelling. Three participants had facial swelling after vaccination. Interestingly, all 3 had facial dermal fillers (2 in the cheeks; 1 in the lips). All 3 cases of swelling were resolved with steroids, but the FDA is planning on noting this in the prescribing information.

Then the external committee voted: “Based on the totality of scientific evidence available, do the benefits of the Moderna Covid-19 vaccine outweigh its risks for use in individuals 18 years of age and older?”

Yes- 20; No- 0; Absention- 1

No one is surprised, as Moderna has put on a very impressive trial with beautiful data to accompany it. As Dr. Hayley Gans stated, “This is a really opportune time to move science forward, and I would say that the evidence — which has been studied in great detail — on this vaccine highly outweighs any issues that we’ve seen”.

Next steps: FDA now either grants or denies emergency authorization. Then a CDC external advisory committee meets (a far more lively and interesting meeting, in my opinion). Then CDC publishes recommendations.

Love, YLE

To read about the fat bubble, check out my previous post here: https://yourlocalepidemiologist.com/covid19-vaccine-side…/