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.
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.
Variant B.1.351 (also known as 501Y.V2; first discovered in South Africa)…
…is, yes, in the United States.
Importantly, it was discovered in two individuals who didn’t know each other AND hadn’t recently travelled. This tells us, epidemiologists, that it’s been spreading within the community (and we just didn’t know about it). We aren’t surprised. This also strongly suggests that others are infected with B.1.351 too. Unfortunately, we don’t know how many people because B.1.351 isn’t easily detectable. PCR tests won’t tell us if someone has this new variant compared to an old variant. PCR tests CAN tell us this with B.1.1.7 (the variant first discovered in the U.K.)
Earlier this week, Moderna and Pfizer confirmed that their vaccines still work against this variant. However, it doesn’t work as well as against the old variants (about a 6-fold difference). Despite this reduction, neutralizing titer levels with B.1.351 remain above levels that are expected to be protective. Moderna is working on a booster that would work much better against this particular variant, just in case we need it down the road.
Today, Novavax also came out with important information about B.1.351…
So, what does this mean? Three things…
This is worrisome news, but we knew this was coming. Stay vigilant. And, honestly, I would be much more worried about what mutations we have not detected in the US. We rank 48th in the world on mutation surveillance.
Have I convinced you yet that it’s important to invest in public health before a pandemic hits?
Our little company from Maryland pulling through! A company that almost lost it all, but making a comeback during the pandemic. This will likely be their first vaccine to make it.
Novavax is a very different “type” of vaccine than Pfizer and Moderna. It uses a coronavirus protein, soapbark tree, and moth cells. Check out my previous post here to orient yourself:
In September, Novavax started Phase III trials in Britain among 15,000 people. Interim results were just released yesterday. What did they find?
My humble opinion: I cannot overstate how ecstatic we are with the efficacy of these vaccines. We were hoping for something over 50%, and we are outperforming. This will, no doubt, help us fight the pandemic. Also, this is super exciting because it’s a different biotechnology. This will help with raw supply issues (eventually). Finally, who doesn’t love a story about an underdog pulling through.
Also my humble opinion: US trials started in Dec, so we won’t see interim results until April. It’s time for the FDA to seriously consider clinical trial data outside of the US for emergency use authorization. This is a global pandemic. It’s time we start fighting it like one.
The CDC ACIP (Advisory Committee on Immunization Practices) had an emergency meeting today.
The purpose of this meeting is to update everyone on the current affairs related to COVID19 vaccinations. There were a lot of big wigs in attendance: new CDC Director, FDA, NIH, DOD, HHS, CDC, AAP, ACOG, AMA, CSTE, AAP (just to name a few).
Here are your cliff notes…
• Enrollment ended in the US. 32,459 people enrolled. As of Jan 21, 26,327 trial participants have received their second dose. 57.8% have a comorbidity and 23.6% are 65+ years old. Trial participants are only getting the standard dose (not the half dose that some in the UK received)
COVID19 epidemiology among kids…
• Kids with the most severe COVID19 are in these groups (and in this order): Obesity; Asthma; Immunocompromised; Chronic lung disease; Cardiovascular disease; sickle cell disease; diabetes; cerebral palsy; down syndrome; hypertension, and renal disease.
• 1,659 cases of MIS-C in 47 states, leading to 26 deaths
Vaccines for children…
• Rationale for pediatric clinical trials: 1) Pediatric burden of disease is significant 2) Disproportionate burden among children in minority communities 3) Indirect effects to the child and society (school, development, etc.) 4) Continued burden if we wait for natural “herd” effects 5) Data suggests that vaccination prevents asymptomatic carriage, thus reversing pandemic more rapidly 6) Safety data are best collected in clinical trials
• Age de-escalation trials will be organized as the following: 6 to <12 years; then 2 to < 6 years; and infants to < 2 years
• True placebos (like saline) are being considered. Another vaccine hasn’t been proposed as a control yet
• Will test multiple dose levels (full, half, and quarter doses)
• Safety of COVID-19 vaccines are reassuring and consistent with clinical trials
• We (the U.S.) are actively collecting safety data from three main sources: V-safe (active surveillance), VAERS (passive surveillance), and Clinical Immunization Safety Assessment Project (CISA) (which investigates individual cases).
• V-safe data has been initially analyzed. 2.08M people have participated in V-safe (out of 21.8M people vaccinated). There are 15,131 pregnancies reported to v-safe (they will follow these women that consent up to 3 months after babies are born)
• See the Figure for the reactions to the vaccines being seen in real-time.
• Anaphylaxis: 50 people reported for Pfizer (out of 9.943M doses) and 21 reported in Moderna (out of 7.581M doses). 90% happened within 30 minutes of vaccination. 80% (Pfizer) and 86% (Moderna) of people had a history of allergies
• VAERS has 196 deaths reported following vaccination. None of them have been causally linked to vaccinations.
Other random notes…
• Prior COVID infection and vaccine side effects: they are designing a study to get a better idea of what’s happening
• Vaccine and transmission: This is a priority. 5,000 healthcare providers and first responders are being assessed for transmission after vaccination. They are getting tested weekly for infection.
• Among 65+ years, 90% of vaccine recipients are White. Speed is compromising health equity
• There is no additional data for delayed doses. The current recommendation remains: don’t delay your second dose more than 6 weeks (42 days) after your first dose
• mRNA vaccines are NOT interchangeable unless in an exceptional situation
Okay, now you’re up to date. Phew.
Here are all the presentation slides if you want more: https://www.cdc.gov/vaccines/acip/meetings/slides-2021-1-27-21.html
Your national epidemiological report (as of Jan 25 7:19PM CST)…
Cases are dropping and they are dropping fast. It looks like we have turned the post-holiday corner. Our 7-day average is now the same as it was in November. Today, 46 states have a decreasing 7-day average of cases and 5 states are plateauing. Not one state has an increasing 7-day average.
Hospitalization trends follow case trends. So, naturally, hospitalizations are looking better too. Hospitalizations in 33 states are decreasing, 16 states are plateauing, and 2 states are increasing (Vermont=27% and Kansas=18%).
Unfortunately, deaths lag hospitalizations. Deaths are still catching up from the holidays. 22 states have decreasing deaths, 18 states are plateauing, and 11 states are increasing. The highest increase in deaths is Arkansas (56%!), closely followed by Hawaii (54%). Yesterday, we had the highest daily death toll of ~4,400 COVID19 deaths in one day. Which is unfathomable. We are predicting 500,000 deaths by mid-February. This would make COVID19 the second leading cause of death in the United States… within 11 months.
We can finally add a new (positive) metric to the report… Vaccinations! 22.7 million doses have been administered. Of which, 3.3M people have received both doses. 41.4 million doses have been distributed. Today, Alaska is the winner with 13,264 per 100K doses administered. West Virginia is a close second with 11,383 per 100K doses administered. North Dakota and Nevada come in 3rd and 4th place. The Western US is, by far, the slowest to administer doses, with CA, NV, and AZ being at the bottom of the bunch. We have yet to gain speed in vaccinations, but this should be coming soon. We are figuring out ways to squeeze a 6th dose out of each vial (by producing special syringes) and deploying mass vaccinations sites. We should get to at LEAST 1 million doses per day in the United States soon. We can’t do this fast enough, as we need to beat the acceleration of the variants.
Every epidemiologist I know is worried about the B.1.1.7 variant (first discovered in the UK). It took 3 months for B.1.1.7 to become the dominant strain in the UK. If this variant continues to spread in the US, we are looking at a March surge that we’ve never seen before. As of tonight, B.1.1.7 is in 23 states with 293 lineage cases reported. But this is among a bias sample of cases. The U.S. ranks 43rd in percentage of cases sequenced. We estimate that B.1.1.7 is ~1% of cases in the United States.
We have 1.5 months to prepare. Early efforts that can limit the spread of the B.1.1.7 variant, such as universal and increased compliance with public health mitigation strategies, will allow more time for ongoing vaccination to achieve higher population-level immunity.
Case, hospitalization, and death data: COVID19 tracking project
CDC variant/immunization rates in regards to infections: https://www.cdc.gov/mmwr/volumes/70/wr/mm7003e2.htm…
Variant cases in the US: https://www.cdc.gov/…/transmission/variant-cases.html
Antibody-dependent Enhancement (ADE)…
A major goal of antibodies is to bind to the pathogen and prevent it from infecting, or entering, a cell. Antibodies that prevent entry into cells are called neutralizing antibodies. Many vaccines work by inducing neutralizing antibodies. However, not all antibody responses are created equal. Sometimes antibodies do not prevent cell entry and, on rare occasions, they may actually increase the ability of a virus to enter cells and cause a worsening of disease through something called antibody-dependent enhancement (ADE).” (CHOP has a fantastic layman explanation of ADE, link below).
A classic example of ADE was a vaccine made for dengue fever in 2016. The vaccine was given to 800,000 children in the Philippines. 14 vaccinated children died after encountering dengue virus in the community. Since, this vaccine has not been used for children under 9 years of age. In the 1960’s, we also saw ADE with a RSV vaccine and an early version of the measles vaccine. Trials for the RSV vaccine were immediately stopped and the vaccine was never distributed. The measles vaccine was fixed and now does NOT induce ADE.
Now in terms of COVID19…
Neither COVID-19 disease nor the new COVID-19 vaccines have shown evidence of causing ADE.
There were early concerns that COVID19 could induce ADE given a few conflicting animal studies. 2 animal studies showed the potential for ADE, while 3 animal studies did not show ADE. It’s clear that ADE is highly dependent on the type of vaccine. The 2 animal studies that showed potential were NOT testing mRNA vaccines (which gives you a small piece of an antibody, rather than the whole antibody). Vaccines with a high theoretical risk of inducing ADE are inactivated viral vaccines. However, it’s encouraging that a recent animal study of an inactivated COVID19 vaccine elicited strong neutralizing antibodies.
Nonetheless, this is why Phase II and Phase III are so crucial in clinical trials. We need to test enough people to ensure that things like this don’t come up. The trials are designed to find potential problems like ADE. And, there has been no evidence of ADE in the trials authorized for emergency use. If there was evidence of ADE, these vaccines would have never made it through and would have been quickly yanked from distribution.
PS There is/was a PubMed nature article circulating stating the contrary. However, the authors did not state their reasons as to WHY they are concerned about it. They just say they are. Which is not helpful. Also, keep in mind that any article can be uploaded to PubMed. If it’s on PubMed, it doesn’t necessarily mean it’s been peer-reviewed… an important distinction.
Here are some great sources:
A science heavy explanation: https://www.nature.com/articles/s41564-020-00789-5
A good layman explanation: https://www.chop.edu/centers-programs/vaccine-education-center/vaccine-safety/antibody-dependent-enhancement-and-vaccines
Ibuprofen (e.g. Advil, Motrin) or acetaminophen (e.g. Tylenol) before vaccination…
It’s recommended that you do not take either of these before vaccination. Pre-treating MAY reduce the your immune response to the vaccine (specifically the ability of B cells to mount an immune response).
“May” is the key word here.
In 2016, scientists conducted a systematic review. They basically took all the studies ever done on this topic (there were 20 total) to try and see whether pre-treatment of Ibuprofen and/or acetaminophen impacted immune response.
Bottom line: We don’t really know whether ibuprofen/acetaminophen impacts immune response. But, the shot just doesn’t hurt that bad. So, if you do decide to take ibuprofen or acetaminophen, take it a few hours after instead of pre-treatment, just to be careful.
As always, this page is for educational purposes only. It’s always best to talk to your healthcare provider before taking any medication (or stopping any medications) and if you’re having adverse reactions to the vaccination.
Many resources and tools came forward this week from sources I trust. These may be helpful for you to make data driven, evidence-based decisions…
Pregnant and breastfeeding…
A group of experts in the fields of OB/GYN, Maternal-Fetal Medicine, Shared Decision-Making and risk communication, Emergency Medicine, and current COVID-19 research at the University of Massachusetts Medical School – Baystate made a decision aid to help individuals who are pregnant, lactating, or planning on becoming pregnant decide whether or not to receive an mRNA COVID-19 vaccine (in conjunction with their healthcare providers). At this site you can get the decision aid in 10 languages.
Differences in mRNA vaccines…
My students made these fliers, which are currently being used for healthcare providers/patients in Texas. But thought I would share for anyone else who would find it useful. It’s been translated in Spanish, Mandarin, and Vietnamese. If you want the PDF, message me your email address and I can send it to you.
Vaccine, Infection, and Herd immunity tracker…
This site was created by Dr. Gu, an MIT data scientist whose expertise is in machine learning to understand data and make practical, accurate predictions. He created some fantastic real-time graphs for the US as a whole and by states. For example, his data found that yesterday Vermont was the first US state to have more people vaccinated against COVID-19 (6%) than infected with COVID-19 (4%). Whoo hoo! (Yes, I know it’s a small state; but take the small wins).
Hope these are helpful!
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.
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).
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.
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…/