Categories
Vaccine

Delayed second dose and (yes) transmission…

Disclaimer: This was the most challenging post I’ve ever written. Translating the complexity of the messy study design, statistical analyses, and implications was not easy and I recognize that I may lose a few of you. Just know that it was not intended. And, honestly, I was thinking about not posting this. But NYT came out with “breaking news” headlines this morning so I thought it was important to get out. Buckle up…

Yesterday, the Lancet (a highly respected journal) released a preprint from the AstraZeneca trial. The purpose of this study was to evaluate whether delaying the second dose had an impact on efficacy and antibodies. This was done post-hoc (so not intended, but since they had the data they ran the numbers). This paper also reported asymptomatic numbers, which can tell us impact of transmission after vaccination.

Delayed dose results:
-A delayed dose does not impact efficacy. In fact, it improves efficacy. Vaccine efficacy after a single dose of vaccine from day 22 to day 90 post vaccination was a combined 76% (59% efficacy at day 22 and 86% efficacy at day 90).
-Protection did not wane before a second dose. Antibody levels were maintained during this period with minimal waning by day 90 day
-The impact of a delayed dose on efficacy was no different among asymptomatic and symptomatic cases
-This study did confirm the importance of the second dose. We can NOT skip our second dose altogether. This boost is important.

Transmission results:
-There were 130 cases of asymptomatic infection.
-(remember important context: this trial had some people that got the doses that were intended (SD/SD) and some accidentally got a half dose first (LD/SD).)
-There was no difference in asymptomatic cases (and thus transmission) among the SD/SD people (41 cases in vaccine group and 42 cases in control group)
-There WAS a difference in asymptomatic cases (and thus transmission) among the LD/SD people (16 cases in vaccine group and 31 cases in control group)

Important considerations that I think are largely missed in mainstream media:
-Not all vaccines are the same. In fact, they are quite different. This is NOT evidence that we can delay Moderna or Pfizer doses
-There were key analyses NOT included in the paper, particularly age. In fact, it looks like they weren’t included in this delayed dose at all (see Figure). It’s not clear whether a delayed dose is generalizable to older adults (55+ years). This is incredibly important to know, as older folks have less neutralizing antibodies.
-It’s obvious that the two groups (those that received a delayed booster vs. those that did not have delayed booster) were VERY different in terms of age, sex, and occupation. We also know that those in the LD/SD group were VERY different in terms of age (younger) compared to those in the SD/SD group. We NEED to take this into account (which the study didn’t do) to imply causality. In other words, it’s not clear whether the increase in efficacy or decrease in transmission was actually from the delayed dose, the low dose, or because of demographics.
-This study did not report variants. And did not report whether delaying a second dose adds pressure on the virus to mutate even more

Bottom line: (And this is all my humble scientific opinion; take it or leave it) This data is messy. And it’s really hard to parse together the story in an accurate way. It looks like a delayed dose of AZ is “okay”. We aren’t necessarily surprised by this. But, I don’t think this study provides enough data to make sweeping policy changes (like delaying a second dose for the older population).

It also looks like we can remain hopeful that vaccines reduce transmission. But this wasn’t the “ah ha” transmission study I was waiting for. The data leads us to more questions than answers. We can’t really answer how transmission is reduced because this was not a transmission study. We simply do not have enough people in this study to be confident in the numbers.

So, it’s too early for me to call re: transmission. I know that NYT called it, but, as a scientist, I just cannot. Sorry guys, I’m just as disappointed as you. But, I AM still incredibly hopeful and you should be too. This is a reassuring sign that the pandemic will, in fact, end.

Love, YLE

PS: I hope other epidemiologists chime in! I had a brief discussion with other epi’s before posting this, but would love to hear other opinions too!

Data Source:
https://poseidon01.ssrn.com/delivery.php?ID=908065002113091029031029004116028092034057081068083017073097002123008109020031031080121005029070024024123121020000093004092067107017108057080016040016089012029024061015090120064080002082029044015123030087062015030073022110003024024070082086119004018090106117113094098107072092070005094074082&EXT=pdf&INDEX=TRUE

Categories
Misinformation Vaccine

COVID19 vaccines will NOT destroy our lives

Apparently an article is circulating: “COVID19 vaccines will destroy our lives”. And, interestingly, it includes a “fact checked” icon at the top indicating it’s been checked by a credible source.

Well, here is a credible source’s rebuttal…

  1. “The COVID-19 vaccine really isn’t a vaccine in the medical definition of a vaccine”.
    This is false. The medical definition is: Vaccine: A product that stimulates a person’s immune system to produce immunity to a specific disease, protecting the person from that disease.
    This is exactly what the COVID19 vaccine does. All of them, regardless of the biotechnology.
  2. “Since mRNA normally rapidly degrades” (this is true) “it must be complexed with lipids or polymers” (this is true). “COVID19 vaccines use PEGylated lipid nanoparticles and PEG is known to cause anaphylaxis.” (This is correct, but taken out of context.)
    PEG has never been used before in an approved vaccine, but it is found in many drugs that have occasionally triggered anaphylaxis. This is particularly true among people who already have high levels of anti-PEG antibodies or experienced severe allergic reactions in the past. Although many types of nanoparticles do have hypersensitivity properties, some newer nanoparticles have been demonstrating ANTI-allergic effects. Controlling the pro and anti-allergic properties of nanoparticles is one of the key elements towards safe use. The U.S. National Institute of Allergy and Infectious Diseases had a meeting mid-December to discuss the COVID19 vaccine allergic reactions and is conducting several studies on it to better understand why people with previous history may have allergic reactions with Pfizer/Moderna COVID19 vaccines. Nonetheless, since this meeting there have been 50 anaphylaxis cases reported for Pfizer (out of 9.943M doses) and 21 reported for Moderna (out of 7.581M doses). This is an anaphylaxis rate of 5 in 1M people (or 0.000503%). This IS higher than the rate of anaphylactic reactions that happen with any other vaccine (1 in 1M people). But, this IS far less than the 70% claimed in the misinformation article. Also (fun fact) PEG is found in toothpaste and shampoo.
  3. “mRNA can signal danger to your immune system and drive inflammatory diseases”.
    I guess this is correct? Although, it’s missing a few key steps. The mRNA instructs our body to create a spike protein then which our bodies make antibodies to. These antibodies then recognize (and, thus, signals danger) if you ever come in contact with the COVID virus. This signal is a good thing, as your body is prepared to fight the virus. If you don’t have this protective signal, then you get an inflammatory disease which has landed more than 93,536 people in the hospital TODAY. Also, you should know you have mRNA floating in your body every second of every day. If free mRNA causes a danger signal, then we are in a lot of trouble (regardless of a vaccine or not).
  4. “Many commonly reported side effects from the COVID19 gene therapy “vaccines” appear to be caused by brain inflammation”.
    The writer doesn’t provide any evidence or context behind this claim. They only state it as fact, so I cannot counter it with science. But, no, the vaccine doesn’t cause brain inflammation. We haven’t seen this and more than 98.3 million doses in 62 countries have been administered.
  5. “Anyone with inflammatory disease (…) are at high risk of dying from COVID19 mRNA vaccines”.
    This is incorrect. No one’s death has been causally linked to the vaccine.
  6. “Genetic alterations may last for life”
    This is false. There are no genetic alterations. At all. The mRNA cannot physically enter the nucleus (which houses our DNA in our cells). Briefly, in order for a mRNA vaccine to alter someone’s DNA, several events would have to occur…
    -mRNA would need to enter the cell nucleus, where DNA lives. However, mRNA do not have the “secret door code” (called nuclear access signal) that would allow it to enter. mRNA vaccines can’t get in.
    -If the mRNA vaccine did get in (which it won’t), mRNA would have to be then converted to DNA. This would require a tool called “reverse transcriptase”, which the vaccine doesn’t have.
    -Also, if it made it into the nucleus, mRNA would then to need to insert itself into the DNA. The mRNA would need a tool called “integrase” to do this, which the vaccine doesn’t have.

Bottom line: I get that we are hesitant. This is the most vaccine hesitancy we’ve ever had; you’re not alone. It’s a trust jump. But it’s a trust jump into decades worth of research and scientists with no ulterior motives other than to save lives and improve the quality of life of our community (and maybe get tenure :)). Please make your decision using an evidence-based, data-driven approach.

Love, YLE

Data Sources:
I would like to thank those Nerdy Girls at Dear Pandemic for encouraging me to write this and ensuring me that it wouldn’t fall on deaf ears. Also, for one of them sacrificing her email address so we could actually read the misinformation being passed around (that’s behind a paywall).

This peer-reviewed scientific article talked about PEG: https://www.sciencedirect.com/science/article/abs/pii/S0378517320307778
This one too: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4849378/
And this one too: https://www.sciencemag.org/news/2020/12/suspicions-grow-nanoparticles-pfizer-s-covid-19-vaccine-trigger-rare-allergic-reactions
Vaccine tracker: https://www.bloomberg.com/graphics/covid-vaccine-tracker-global-distribution/
Anaphylaxis rate: https://www.cdc.gov/vaccines/acip/meetings/slides-2021-1-27-21.html
About the author behind this misinformation: https://www.washingtonpost.com/investigations/2019/10/15/fdc01078-c29c-11e9-b5e4-54aa56d5b7ce_story.html
Pfizer safety data: https://www.fda.gov/media/144245/download
Moderna safety data: https://www.fda.gov/media/144434/download
Long-term effects of the vaccine: https://yourlocalepidemiologist.com/long-term-effects-of-the-covid19-vaccine/
The vaccine got to us incredibly fast: https://yourlocalepidemiologist.com/the-vaccine-got-to-us-incredibly-fast/
mRNA and our DNA: https://yourlocalepidemiologist.com/mrna-and-dna/
Deaths and the vaccine: https://yourlocalepidemiologist.com/deaths-and-the-vaccine/

Categories
Children Vaccine

Mom to baby transmission of antibodies

We are seeing more and more evidence that moms pass COVID19 antibodies to their babies…

There have been 3 important studies that have recently come out telling the same story…

  1. Between April and August 2020, scientists tested 1,500 women who gave birth in Philadelphia. They found…
    -83 had COVID antibodies
    -Among the 83, 87% of their babies tested positive for IgG antibodies (the long lasting antibodies) after they were born
    -Transferring antibodies was not different among infants born to mothers with asymptomatic or symptomatic illness
    -In 25% of the babies, their antibody levels were 1.5 to 2 times higher than the mother’s concentration
    -The longer the time period between the start of a pregnant woman’s COVID infection and her delivery, the more antibodies were transferred to the baby
  2. From April 4 to July 3, 2020, in a single university hospital in Denmark, 1,313 women took part in a study.
    -28 women (2.1%) had antibodies against COVID
    -67% of newborns delivered by mothers with antibodies had COVID IgG antibodies.
    -Neonatal outcomes (like birth weight, APGAR value, amniotic fluid, CPAP, and blood pH) were not affected by the antibody status of the mother
  3. Another study enrolled 22 COVID+ moms and 34 COVID- negative moms and tested their cord blood after birth.
    -Antibody transfer was efficient after second-trimester infection
    -While antibodies do pass, they do less efficiently than the antibodies produced after vaccination for flu and whooping cough. But this effect was only observed in third-trimester infection.

Like always, we still have a lot of unanswered questions. We need more research to better understand two things:

  1. Do vaccine-generated antibodies behave comparably to antibodies from COVID infection?
  2. Are antibodies protective against newborn infection? If so, at what concentration?

Bottom line: We already know there are benefits to pregnant women getting vaccinated. These studies suggest that there also may be benefits to the baby. Interestingly, timing of infection (or possibly timing of vaccination) may be important to ensure baby getting antibodies.

Unfortunately, pregnant women were excluded from clinical trials (which has stirred quite the debate among scientists), so these questions will take quite a bit of time to answer.

Love, YLE

Data Sources:
https://jamanetwork.com/journals/jamapediatrics/fullarticle/2775945
https://journals.lww.com/greenjournal/Fulltext/2021/01000/Severe_Acute_Respiratory_Syndrome_Coronavirus_2.7.aspx
https://www.cell.com/cell/fulltext/S0092-8674(20)31749-9

Categories
AstraZeneca Moderna Novavax Pfizer Vaccine Variant

Updated Vaccine Table

Things are starting to get complex. So, I updated my very bland vaccine table from December. I hope it’s helpful in keeping track of all the moving parts.

Love, YLE

Categories
Antibodies Vaccine Variant

Bad news about the circulating variants…

If you remember, the South Africa variant (better known as 501v2), Brazil variant (better known as B1.1.28/501.V3), and the UK variant (better known as B1.1.7/501Y.V1) have all recently grabbed the attention of scientists because each have mutations on the spike protein. These are important to investigate because the spike is the keys to our cells. In other words, the virus can mutate to make a smarter key.

There are two new pieces of information this week/today.

First, the 501v2 (South Africa) variant…

-What happened? On Jan 20, a preprint came out from Rockefeller University. They took the antibodies of 20 volunteers who received an mRNA vaccine and mixed it with viruses containing the mutations. This experiment, called an antibody neutralization assay, enables the researchers to determine whether vaccine-induced antibodies will be effective against the new variants of virus circulating globally.

-What did they find? The antibodies effectiveness against the mutations was reduced by a small (but statistically significant) degree (ranged from a 1- to 3-fold reduction).

-What does this mean? The vaccine is working against 501v2 (thanks to the polyclonal response), but these mutations *may* impact the efficacy of the vaccine. We need more “real-world” studies, in addition to the well-controlled, test-tube studies.

Second, the B.1.1.7 (UK) variant…

-What happened? Today, NERVTAG (New and Emerging Respiratory Virus Threats Advisory Group) met to discuss new studies on B.1.1.7. They previously reported a study in which there was no increase in death due to the new variant. However, with more time comes more data.

-What did they report? There are three new studies (one by The London School of Hygiene & Tropical Medicine, one by Imperial College London, and one by University of Exeter) that all showed that the B.1.1.7 is more deadly by about 1.65 fold.

-What does this mean? “There is a realistic possibility that B.1.1.7 is associated with an increased risk of death compared to the virus without these mutations.” While the risk of death remains low, this does increase it by a significant amount. There is a limitation to these studies… Only 10% of COVID19 deaths have their virus coded to know which mutation the person had. In other words, this could be a bias sample. Deaths are lagged from cases, so the more time goes by, the more and more accurate of a picture we will get.

Bottom line: The virus is getting smarter. Slowly but surely. This underscores the need to vaccinate as many people as quickly as we can, because these mutations are signals of antigenic drift.

Love, YLE

Data Sources:

Rockefeller study: https://www.biorxiv.org/…/2021.01.15.426911v1.full.pdf

NERVTAG meeting minutes: https://assets.publishing.service.gov.uk/…/NERVTAG…

I knew the SA story was coming out at some point this week, so I prepared with two brilliant colleagues, Dr. Jessica Steier (public health scientist) and Dr. Andrea Love (immunologist). They are both doing wonderful work at The Unbiased Science Podcast (www.unbiasedscipod.com).

Categories
Children Vaccine

Kids and COVID-19 vaccination…

We have begun age de-escalation trials. Age de-escalation means that phase I and II trials are conducted first in adults, then in older children, and finally, if relevant, in small children. Vaccines need to show safety in each stage in order to move down in age.

Vaccine sponsors have already started trials for 12+ and are drafting trial plans for younger kids. Given that kids are usually asymptomatic, the trials will probably involve regular, frequent testing. First and foremost, scientists will be looking at safety. And, unlike adult studies, the plan is for the trial endpoint to be immunity (instead of disease).

Here is the status for the age groups:

12+ years: Pfizer started in October and has now finished enrollment. 2000 kids (aged 12-15) are enrolled. Moderna started in December and are still enrolling. They are aiming for 3000 kids (aged 12-17) to enroll. Moderna is starting to open more sites (see link below to find the cities). AstraZeneca is starting next month (but not in the US). Kids in all three of these trials will receive the same dose as adults. Many are hopeful that, with a bit of luck, we can have vaccines for this group by Fall 2021.

5/6-11 years: Starting late Spring. Pfizer starting Phase I in April.

<5 years: Don’t expect data until 2022

Kids have fared much better than adults during this pandemic, mostly comprising of asymptomatic infection. So, why do kids need vaccines?

1. Herd immunity. Children are part of the transmission chain, so eventually, if we want to get to the stage of herd immunity, they have to be included. Especially, if this virus is mutating to be more transmissible. The more transmissible, the higher herd immunity we need. We are hopeful that the vaccines reduces asymptomatic spread, we just don’t know by how much. We are still waiting on studies.

2. Disease. There are kids that get very serious disease, like MIS-C, from this virus. The vaccine will provide protection among the few that will get the disease.

3. Morbidity. Long term morbidity is something we still know very little about. Especially among kids.

CDC’s Advisory Committee on Immunization Practices (ACIP) is meeting on January 27 (10a-5p EST) to discuss this very topic.

Here is the meeting agenda: https://www.cdc.gov/…/agen…/Agenda-2021-01-27-508.pdf…

Here is the webcast link: https://www.ustream.tv/channel/VWBXKBR8af4

It is open to the public. Should be a very interesting discussion. Like always, I’ll be happy to provide you with cliff notes. Stay tuned.

Love, YLE

Data Sources:

Ethics on child vaccine trials: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3601712/

Moderna Trial Info: https://clinicaltrials.gov/ct2/show/NCT04649151

Pfizer Trial Info: https://clinicaltrials.gov/ct2/show/NCT04368728

Kids and Herd Immunity: https://www.theatlantic.com/…/should-kids-get…/617762/

TeenCove study (if you want to enroll): https://connect.trialscope.com/…/a6dd51e8-c0a0-4ad5…/

Categories
Antibodies Vaccine

FAQs

I’m getting flooded with messages and questions! Which is fantastic, but I do this in my “free” time and can’t possibly get back to each and every one of you. Here is my attempt to answer a lot of your questions all at once…

Antibody test after vaccination…

Do not get an antibody test after your vaccine. The vaccine gives your body instructions on how to make specific antibodies to fight the virus. These are not necessarily the same antibodies that antibody tests look for. So your test may be negative, but this is not indicative that the vaccine is not working.

“Natural” vs “vaccine” antibodies…

The physical antibody you get from either are exactly the same. The difference, though, is the strength of your response. There could be a difference in your immune response if you got “naturally” infected compared to vaccinated. Research shows that “natural” antibodies do fade off among 10-15% of people. The only way we could actually know this is if we tested your antibodies every day, and we aren’t going to do that. We know that vaccination provides the perfect formula (this is the purpose of Phase I and II trials).

Delaying first dose to ensure second dose…

Do not do this. Get your first shot if you are eligible and can get an appointment. Odds are, you will get your second dose on time. If not, immunology tells us that the vaccine doesn’t require the precision of a couple days or even a week. Beyond that, we don’t know. But don’t delay a high probability event (getting a vaccine and it working) with a low probability event (getting a delayed second dose and it not working).

Autoimmune diseases and the vaccine…

The CDC states that people with autoimmune conditions may receive an mRNA vaccine. However, there is no data currently available on the safety of mRNA COVID-19 vaccines for you. Individuals from this group were eligible for enrollment in clinical trials. Talk to your healthcare provider.

Immunocompromised and the vaccine….

The CDC states that people with HIV and those with weakened immune systems may receive a COVID-19 vaccine. However, they should be aware of the limited safety data:

* Information about the safety of mRNA COVID-19 vaccines for people who have weakened immune systems in this group is not yet available.

* People living with HIV were included in clinical trials, though safety data specific to this group are not yet available at this time.

People with weakened immune systems should also be aware of the potential for reduced immune responses to the vaccine, as well as the need to continue following all current guidance to protect themselves against COVID19. Talk to your healthcare provider.

Medical advice…

I cannot give medical advice. I’m not qualified. And, even if I were, I don’t know your medical history. Please talk to your healthcare provider about side effects, about whether you should get the vaccine, about symptoms, about your history of allergies, etc. And if they aren’t willing to talk to you about the vaccine, please find another provider.

The CDC website actually has some fantastic information. But it is difficult to navigate, I get it. I’m certainly not going to compete with the CDC, but you can also always use the search function on my blog. Just throw in a word on the topic you’re interested in, and the science should pop up. I also “tag” my posts with “themes”. So, for example, you can select “children” on the list of categories and all my posts with that tag will show up.

Love, YLE

Data sources: https://www.cdc.gov/…/recomm…/underlying-conditions.html

https://www.cdc.gov/coronav…/2019-ncov/vaccines/facts.html

Categories
Leading Cause of Death Long-term effects Vaccine

Deaths and the vaccine…

It’s extremely important that epidemiologists (and for those trying to understand epidemiology) understand the difference between correlation and causation.

When I teach this topic to my graduate students, I start with a classic example…When ice cream sale go up, drownings increase. Does ice cream cause drowning? No. It’s tempting to assume that one pattern causes another. However, correlation might be coincidental or it might be a result of both patterns being caused by a third factor. The third variable here is a hot summer day, which boosts ice cream sales AND swimming, and thus drownings. In other words, correlation (ice cream sales and drownings) does not imply causation (ice cream sales cause drownings).

The same can be applied to a wide variety of public health issues, including the latest hot topic…deaths and vaccines.

As of this morning, Norway reported that 33 people (aged 75+ years) died a few days following their COVID19 immunization. Germany is also investigating 10 deaths. After reading headlines, it’s easy to make the assumption that the vaccine caused the fatal outcome. However, there is a very important third factor… frail, older adults die, and die more often. In Norway, an average of 45 people die each day in nursing homes because of underlying issues. The 33 deaths after vaccination do not represent an excess of deaths. When there’s a mass vaccination campaign, the overlap of vaccination and death is going to happen. It just is.

However, I don’t want to undermine the importance of investigating causation. Norway is investigating 13 of these deaths. And while the Norwegian Medicines Agency and the National Institute of Public Health are still not certain of causality, they did state the possibility that the vaccines’ side effects (like fever) may have exacerbated underlying medical issues that are not dangerous in fitter, younger populations. Dr. Madsen (Director of the Norwegian Medicines Agency) stated: “We are not alarmed or worried about this, because these are very rare occurrences and they occurred in very frail patients with very serious disease”. As of today, 48,000 Norwegian nursing home residents have been vaccinated and did not die.

These deaths will have no impact on Norwegian Medicines Agency’s vaccination strategy. They are still going to first offer vaccinations to those 75+ in nursing homes. But they do urge 80+ patients and their families to discuss the risks and benefits of vaccination with their doctor prior to vaccination.

Love, YLE

Update: Many of you are confusing temporal correlation with direct causation. COVID19 and death is a direct causation evidenced by excess death analyses (search “excess deaths” in my blog). In other words, if COVID19 didn’t infect the patient, they would still be living.

Data Sources:https://www.bmj.com/content/372/bmj.n149

Categories
Vaccine

The vaccine got to us incredibly fast

Americans got their vaccine in 9 months. This shatters all records of previous vaccines. (Before the pandemic, the fastest vaccine was made in 4 years). But it doesn’t mean scientists were rushed. Scientists had a few key things on their side that helped speed up the timeline without sacrificing quality.

  1. Previous research.

We relied heavily on our previous SARS and MERS work. We were able to do this because COVID19 is roughly 80% identical to SARS. In 2003, we created a vaccine to recognize the SARS’ spike and started moving through clinical trials. However, trials ended because the SARS epidemic faded off on its own, and thus money dried up. If money didn’t dry up, we could’ve had a COVID19 vaccine much quicker. However, this also meant that we didn’t have to start from scratch in 2020. We were able to skip the pre-clinical and academic research (which takes years) because we were already very familiar with spike proteins, coronaviruses, and vaccines. Also, because of this SARS work, pilot factories were already planned to produce enough vaccines for trials. This groundwork was paramount to getting the vaccine trials up and running in March 2020.

2. Money and resources.

Never, in the history of public health, have we had this much money and this many people working on one disease at one time. Normally, researchers need years to secure funding, get approvals, and study results piece by piece. For example, researchers are typically dependent on grants. In order to get grants, you need data and months (if not years) go by between Phase I, II, and III in order to get data to secure money. But the pandemic is not “typical”. Scientists didn’t need to do this because of the monetary support from the federal government. They were able to just go.

3. High levels of disease.

The FDA specifies, before trials, the efficacy threshold needed to be considered for emergency use. For COVID19, companies needed a higher than 50% efficacy rate. In order to get to that threshold, trials needed to drag on until enough people got infected with COVID19. For example, in Phase III of Pfizer, scientists needed 162 people to get COVID19. Then they could compare how many of these 162 people were in the vaccine group and how many were in the placebo group. COVID19 transmission is rampant in the United States. They needed less people to enroll in the study to reach this threshold. This isn’t always the case in RCTs.

4. Production.

Sponsors were able to start producing the vaccine WHILE the vaccines were currently in trial. This is also very unusual. They were able to do that because governments, around the globe, were willing to put bets on the vaccines (risk vs. reward). Building and manufacturing early shaved off a ton of time, as the vaccine sponsors could anticipate that factories would be useful for a future vaccine.

5. Overlapping phases.

The scientists didn’t wait for Phase I to complete before moving onto Phase II. And didn’t wait for Phase II to end before moving onto Phase III. This isn’t the first time in history this has been done. In fact, this type of design even had a name before the pandemic: seamless and adaptive design. We basically save a ton of time by removing the “white space” between phases. For example, when we combine Phase II and Phase III, scientists evaluate “dose selection” (which is typically determined in Phase IIb) and “confirmation” (typically Phase III) into one trial. There’s quite a few advantages to this type of design (in addition to saving time). First, there’s more efficacy/dose information prior to triggering Phase III. Also, there’s higher chance of patients within the trial to be treated with efficacious and safe doses.

6. Enrollment
As a researcher, it’s incredibly difficult to find people to volunteer for studies. One follower also mentioned this: “I manage trials and my current study aims to find 240 subjects in TWO years”. The amount of people who flooded to volunteer for these studies is incredible. This couldn’t have been done without each and everyone of them.

Bottom line: Speed does not mean rushed. It meant, in this case, leveraging a whole lot of smart people, money, and decades of previous work to get us a vaccine in 9 months.

Love, YLE

Data sources:

More on seamless design: https://pubmed.ncbi.nlm.nih.gov/20724313/

More on timeline (with cool graphics to play around with): https://www.nytimes.com/interactive/2020/04/30/opinion/coronavirus-covid-vaccine.html

Categories
Vaccine

Sinovac and Sinopharm vaccines…

Unlike mRNA vaccines (Pfizer and Moderna) or viral-vector vaccines (AstraZeneca and J&J), Sinovac and Sinopharm biotechnology takes a more traditional route. The science is a whole lot more straightforward. 

Scientists grow the COVID19 virus in monkey liver cells. Then inactivate the virus by mixing it with a chemical (called beta-propiolactone). The chemical disables the virus by bonding to its genes and, thus, the virus can no longer replicate once injected. The vaccine, though, still looks and feels like COVID19 to our immune system, so it will trigger the memory immune response.

A Chinese company, called Sinovac, created a vaccine called CoronaVac. This is a 2 dose regimen taken 2 weeks apart. Phase III was rolled out in Brazil, Indonesia, and Turkey.

Efficacy of Sinovac has been a rollercoaster to follow. Turkey initially announced the vaccine had 50% efficacy, but then reported 91% efficacy. On January 7, Brazil reported an efficacy rate of 78%. But, shortly after, they walked back saying it was 78% only in one subgroup and the efficacy is “just over 50%”. (The 50% is important because it’s the threshold for approval). Phase III results have yet to be published, so no one has seen this data yet. Its a bit challenging to parse together what’s actually going on until that comes out. 

Another Chinese company called Sinopharm created a vaccine called BBIBP-CorV. It has had a bit more success with efficacy. It’s also a 2 dose regimen but 3 weeks apart. Phase III was conducted in UAE, Peru, and Morocco. Sinopharm reported 79% efficacy in Phase III.

This type of vaccine (similar to viral-vector vaccines) is incredibly easy to store. It, too, will have an incredible impact on the global pandemic. 

Love, YLE 

Sinovac Phase I/II: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30843-4/fulltext

Sinopharm Phase I/II: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30831-8/fulltext

Nature figure: https://www.nature.com/articles/d41586-020-01221-y

More really great information on this type of vaccine: https://www.nytimes.com/interactive/2020/health/sinovac-covid-19-vaccine.html

Vaccine overview: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551521/pdf/41392_2020_Article_352.pdf?fbclid=IwAR3YfwYlUCBxC5V5YOW_AQArUMM_KjbPFHtlWUmklWQHKjQTR8DqIzrsP34