a schedule board with 11a-5p COVID Vaccine and 2:30 Ice Cream, among other things
This is the best daily schedule Ever.

It’s all alphabet soup in the end

So Johnson & Johnson have submitted their data to the FDA for emergency use authorization (that’s EUA for those of you who speak alphabet soup). The data on this one are super interesting, so I’m going to talk about some new things we know! 

What is an EUA, anyway?

An Emergency Use Authorization means that (1) an emergency exists involving some kind of serious or life-threatening health condition (it is all alphabet soup here) (2) there are no traditionally-approved treatments for this condition (3) the FDA have reviewed the existing data on an intervention (could be a procedure, a medication, a device, etc) and it looks like it might have a benefit even though the full criteria for FDA approval have not been met. 


Sometimes, later information comes out that makes it clear that the intervention is not, in fact, helpful, and the EUA gets revoked. We have seen that several times with this pandemic – with certain COVID tests, with certain medications, and even with certain kinds of personal protective equipment. The FDA continuously evaluates the information that’s available to them. 


What manufacturers are hoping for, of course, is that the long-term data will support full FDA approval in the end. An EUA is not a shortcut to approval – it’s a tool that we have to use when lives are at stake and we can’t afford to wait for the usual (potentially years-long) process to grind along. 


What about the Johnson and Johnson vaccine? 

J&J applied for EUA for their vaccine on Friday. It’s a single-dose adenovirus vector vaccine (they are still running trials on a 2-dose version), so this vaccine works a little differently than the two vaccines currently on the market. Basically, J&J are using an adenovirus – a particular type of virus that’s really good at getting the body’s attention, thanks to the fact that they infect pretty much everybody (this is another common cold-causing virus) – and have modified it so that it’s not so good at actually copying itself any more. What it does do is present a set of instructions to the cells (just like the mRNA vaccines) to make viral spike proteins.


This vaccine uses DNA — so it depends on the body to translate the instructions for making spike proteins into mRNA and take them to the factories. It can’t actually affect the DNA that’s inside your cells already (and neither can the mRNA vaccines); it simply doesn’t have the enzymes to unzip your cells’ DNA and break it apart. 


J&J enrolled a little over 43,000 people in their global trial, and saw 468 symptomatic cases of COVID-19 in that trial. They designed the study to look for moderate to severe COVID-19 at 14 and 28 days after vaccination, as well as for all symptomatic infections. They also did genetic tracking on the types of COVID-19 infections they saw. 


So what did they find? A couple of interesting things. 


The vaccine was 66% effective in preventing moderate to severe COVID-19 at 28 days after vaccination — and there was enough data to say that in the US, it’s more like 72%. That’s not as good as the 94-96% prevention that Pfizer and Moderna have reported, but it’s still pretty substantial; about as effective as the adult pneumonia shot (Pneumovax23 in the US). There’s a bit of more important information in the report, though: J&J reports no cases of COVID-related hospitalization or death after day 28 in the vaccinated group. 


This is a vaccine that protects people. It’s a good vaccine! 


It may not be quite as amazingly amazing as Moderna and Pfizer’s prevention numbers (although preventing hospitalization and death is a BIG deal), but it has pretty solid safety information: there were no cases of anaphylaxis reported during the trials, and the placebo arm reported higher rates of serious adverse effects than the active vaccine arm. J&J notes that this is actually not the first vaccine candidate using this technology (their Ebola vaccine was actually approved in Europe in 2020), and that they’ve seen similar safety profiles in those long-term trials. This is a vaccine whose driving technology has a longer-term track record.


This vaccine also has some ability to see through a false nose and sunglasses! It’s not perfect; it did show decreased efficacy against the South African variant B.1.351 (remember: this variant coronavirus is super friendly AND doesn’t quite look like its wanted poster), but still protected people about half the time. That’s not bad! It’s about as good as the old shingles shot was for shingles prevention (the new one is almost 90%).


We have some pre-print data that suggests Moderna and Pfizer’s vaccines work to neutralize the mutant viruses in test tubes — but humans are not test tubes, pre-print data still needs outside eyes to look at it, and so we don’t know what the real-world effects will be. 


And this is where I remind you that variant B.1.351 has been seen in the United States, and this is why — even when you’re vaccinated — it’s still important to wear your mask, keep your respectful social distance, and avoid spending time with groups of people indoors, especially if there is eating and drinking involved.



a vaccine certification

Who should not get vaccinated (right now)?

Vaccine eligibility in Indiana (this is where I live, so it’s the state whose health department notifications I receive) was updated this morning to include people ages 65 and up. If you (or your loved one) need to sign up then it can be done through ourshot.in.gov or by calling the 211 line. Your local Area Agency on Aging (wow, say that three times fast) can also assist you. If you or your loved one are a long-term care resident then several pharmacy groups have been working to vaccinate people where they live. If you are a health care worker or you come into regular contact with infectious material then you can also be vaccinated (ourshot.in.gov or 211). 


I’m told that your public library may be another place where you can get help signing up for your vaccine (I cannot say enough good things about public libraries)!


My Facebook feed is full of people I love getting vaccinated on a regular basis, and I’m so excited about that! I do want to cover a question I promised I would come back to in more detail, though: 

Do you have any info on not getting a vaccine if you have allergies?

Things I know should make you talk to your doctor or delay signing up: 

  • If you have a known allergy to PEG (polyethylene glycol), polysorbate, or any other of the (very short) list of vaccine components, talk to your doctor before you sign up because you may be at increased risk of an allergic reaction
  • If you have a history of severe reactions or anaphylaxis to another vaccine or infused (IV) medication, talk to your doctor to make a decision based on your particular case. 
  • If you had your first shot and had anaphylaxis (or any serious reaction) to that shot, talk to your doctor before you commit to another. 
  • If you have dermal fillers (a type of injectable treatment for wrinkles and aging skin) then your response to the vaccine may include a (treatable, mild) reaction at those sites and you should talk to your doctor to know what to expect.
  • If you are actively under quarantine for COVID-19 exposure please don’t come in to get vaccinated while you are under quarantine. We don’t think your immune response will be fast enough to prevent development of COVID-19 and you’ll expose everyone at the vaccination site.
  • If you are positive for COVID-19 please wait until your isolation period is over and your symptoms are resolved. You may consider delaying a little longer (up to 60-90 days), depending on your personal risks of exposure and the vaccine supplies where you are located. 
  • If you’ve had another vaccine (flu, shingles, pneumonia shot, etc) you should wait 14 days before your coronavirus vaccine (and wait 14 days after it before you get any other vaccines) because we don’t know if there are any interactions that would affect your immune system’s response. 
  • If you received a monoclonal antibody infusion for COVID-19 specifically, we are recommending you wait 90 days after the infusion, because we don’t know exactly how those synthetic antibodies will interact with the vaccine.
  • If you have HIV or are immunocompromised, we have some data on how the vaccines work, but not as much as for people with more robust immune systems. These vaccines CANNOT give you COVID-19 (remember that post on how they work?) but you should talk to your doctor about the latest information.  
  • If you are in super fragile health and a day or two of feeling awful might actually kill you, talk to your doctor before you get your shot. 


And one more: If you are pregnant. 


The World Health Organization has released a statement about pregnant people and the Moderna coronavirus vaccine, and it’s just about as long as anything I could have written. I’ll try to summarise: 


“We don’t have enough data about this vaccine in pregnant people to make a definite statement about its safety (or about how well it works). The science behind the vaccine suggests that it should be safe, and animal studies have not shown any harm, but until we have a meaningful amount of data from actual pregnant people, you should talk with your doctor about your personal risk of contracting COVID-19 and severe disease, then make a decision based on the benefits to you and the fact that we don’t know for sure whether there are risks.”


That’s still a lot. The CDC’s recommendations at this point take a couple of pages and are roughly the same (“people who are pregnant and part of a group recommended to receive a COVID-19 vaccine may choose to be vaccinated”) 


What this amounts to is: We think this is probably safe, but we don’t have the data to back it up yet, and as responsible scientists we feel that we need to tell you we are making an educated guess about the safety of these vaccines in pregnant people. 


That’s a pretty long and relatively specific list of reasons not to get vaccinated. 

A couple of things that are not on the list:

  • Medications: I am not currently aware of any medications (other than the vaccines and monoclonal antibodies I mentioned above) that are a concern with the COVID-19 vaccines. The trials were performed on people with a variety of common diseases, and people were instructed to keep taking their regular medications. There’s no noted concern in the published data for any medication interactions. 
  • There’s been a little chatter about whether it’s okay to use acetaminophen, ibuprofen, and aspirin type medications to treat your post-vaccine symptoms. A review paper published in 2016 looked at the available data on whether these medications affected your immune response. It turns out that they might decrease your response a little bit! However, that effect is small, and because vaccines are designed to create a robust (strong) immune response, it may not make a real-world difference. We don’t know for sure.
  • Asthma: We are good to go, asthmatics! If you have particularly severe asthma, then check with your doctor. 


Happy vaccinating! 



a vaccine parking sign

A long week

This week has been complicated. I owe a lot of people gratitude – more, I suspect, than I know – for the grace I have been given. You had better things to do than to wait an extra hour in the office/wonder overnight if you’re going to get the medicine you need to feel better/change your plans because I forgot what mine were. So thank you…because you know who you are.

My rural hospital has administered over 3,000 COVID-19 vaccines, and we continue to vaccinate more than 150 people a day. That is a number that makes me smile.

This week has been a very busy week in COVID news! I am going to try to put together some information over the weekend, but here’s what I’ve been hearing about (did I miss anything? Let me know!) 

  • The B.1.351 COVID-19 variant (South African) appears to be wearing some pretty rockin’ sunglasses and auditioning for the Virus Cheer Team. I’d like to take a look at what we know about the existing (and upcoming) vaccines and their effectiveness against this variant in particular.
  • Speaking of upcoming vaccines, Johnson & Johnson have released the next round of their data and it’s pretty interesting. What do we know about the new kid who’s getting ready to move into the vaccine block?
  • There’s a lot of talk about wearing two masks these days! What does that mean, why would we do it, and is there any good practical information that doesn’t come in an infographic about covering your nose (cover your nose!)?
  • WHO has made a statement about vaccine administration with pregnant people that merits an update to a previous post about vaccines and pregnancy (short version: Definitely talk to your doctor if you are a pregnant person who is eligible for the vaccine). 
  • We’re having conversations about teachers returning to schools in several major metropolitan areas, as well as smaller ones – some with, some without the vaccine. What does the science say about in-person schooling?

That’s a super busy news week! It’s a pity I’ve been in meetings pretty much all my spare minutes – although some of them were very interesting (I got in on a CDC webinar, and the Indiana Department of Health is still working on a lot of things that aren’t COVID-19 too.)

What did I miss?




Dr. Nykki's mom and granddad
Two people who are excited about this vaccine – my mom and her dad – from my 2017 archives

Introducing Mom…

Today, my mom called me to let me know that she had received her first shot of Pfizer’s vaccine. She’s a pretty healthy not-too-much-over-70 woman who assured me that the biggest symptom she has had so far was a feeling of amazement and dawning relief. 


We are all carrying around a lot of stress and anxiety — for so many reasons — and I think it’s important that we continue to acknowledge that. It’s okay to feel anxious! It’s also okay to be tired of living under a burden of constant vigilance, because that is emotionally and physically exhausting, and we have been living under COVID vigilance since roughly March of last year to varying degrees. 


Take care of yourself, if you can, this coming weekend. Go outside if that’s feasible for you, and take some time to breathe fresh air (if you are quarantining or isolating, then take appropriate precautions to avoid others breathing your freshly-exhaled air, but get some fresh of your own). Write a letter to yourself or so  meone you care about (It’s okay! Wash or sanitize your hands after handling your mail because that’s good practice any time you handle something a zillion people and machines have been touching, but the risk of getting COVID from your friend’s letter is minimal, if any). Make some tea, if you enjoy tea. Take a long bath. Get dressed in nice clothing if you have been living in sweats. Exercise if you have not been (exercise outside if you can): exercise triggers your body’s natural antidepressants. 


None of this is going to make it okay that we’re living lives of vigilance and separation. But the really amazing thing about human beings is how good we are – when we let ourselves – at finding creative ways to solve our problems. Give yourself permission – because I am giving you permission – to be your most amazing self this weekend. I’m interested to know what that looks like, if you decide you want to share.

Mom had a vaccine question for today’s diary: 


What happens if I don’t get my second dose right at 21 days (or 28 days)? What if my second shot is late?  


Short answer: 


You’re still considered to be fully vaccinated, even if your second shot is waaaay after your first, although we don’t have data to give you a definite answer beyond 6 weeks yet. That’s consistent with our recommendations for all the routine vaccinations you’re likely to get — we don’t generally restart shot series. 


Long answer: 


Most vaccines – regardless of the trick they use to do it – work by invoking your immune system’s short-term defenses and long-term memory cells. For vaccines that are given in a series (like your childhood shots are), each shot builds on the memories of the one before it, reinforcing the protective responses of your immune system to create long-lasting defenses. 


Let’s look at tetanus as a great example. The idea behind tetanus vaccination is to protect you from Clostridium tetani infection, which causes tetanus (cheerfully known as lockjaw to some folks). C. tetani lives in dirt and makes a toxin that causes serious muscle spasms, and getting tetanus naturally does not protect you from future infection (yikes!). Fortunately, we have an extremely effective set of vaccines to help your body protect itself against tetanus. We measure that protection by checking levels of tetanus antitoxin. 


The first dose of a tetanus vaccine creates almost no protection — but it primes your immune syste for the next; after the third dose nearly every vaccine recipient has high enough levels of tetanus antitoxin to safely step on a dirty nail without getting lockjaw (I don’t recommend stepping on nails regardless). That protection lasts for about 3-5 years, so we give a booster shot to kids who are entering kindergarten, and another one in the early teenage years. At that point you may be protected to some degree for 20-30 years because your immune system remembers – but we still currently recommend a booster every 10 years to keep the memories fresh, and if you happen to encounter a dirty nail we’re going to give you a booster dose to make extra sure you stay safe.


If you happen to miss out on one of those childhood doses, we don’t make you restart the series – because we’re counting on the long-term memory cells (remember the memory B and memory T cells? We talked about those a couple of weeks ago) to pick up where they left off with the next vaccine in the series. For almost every vaccine on the market (exceptions: certain cholera and typhoid vaccines), that remains true; we recommend a minimum time to wait between vaccine injections in order to let your body finish round one of recognizing and remembering so it can launch its best response to round two, but there is no maximum time. 


The data we have at this point is only good for a delay of about six weeks between vaccines, and only on the Pfizer vaccine. Because Moderna’s vaccine is so similar, we are making an educated choice to treat it similarly, and as we continue to vaccinate more people – and make difficult decisions about how to distribute a limited vaccine supply – we may learn more (scientists love data! Even if it’s not in a controlled experiment) and be able to expand that information. 


For now, if you have gotten two doses of the Pfizer or Moderna vaccines – spaced at least 21 (Pfizer) or 28 (Moderna) days apart (the CDC says you can have a grace period of up to 4 days early), then you are considered to be fully vaccinated. 


And thanks for asking the question, Mom!


a negative BINAXNow Covid test

My brain is wired for panic

At one week out from my vaccine, I’ve had no new concerns. I have friends and family members reporting fever, fatigue, malaise, nausea, and vomiting – sometimes after the first dose – so I’m grateful to my immune system for all the favors it’s doing for me. Keep it up, immune system!


I’ve had a news article come up on several of my feeds lately, and so today’s diary is going to be about the Norway data and reading breaking medical news articles.


The article in question, depending on your news source of choice, begins with the headline “Norway Raises Concern Over Vaccine…” or “23 Die After Pfizer Vaccine…”; and that’s certainly a headline that will raise concern. I’m concerned! But we’ve been talking a lot about science lately, and the way that our brains tell us things that may or may not be strictly true, so I’m going to take you through a deep dive into the publicly available information and what it means from a scientific standpoint.


The article I’m using is from the British Medical Journal (a peer-reviewed publication with reasonable standing in the medical community, so a source I trust), but it reflects most of the same information you’ll find from any news source that is doing its research: Norwegian physicians had reported 23 deaths in patients who had recently received the Pfizer coronavirus vaccine. Those deaths were in care home patients (nursing home patients), many of whom were “very frail”. Some of those patients underwent autopsies and Norwegian health authorities felt that the side effects of the vaccine may have contributed to the deaths of the patients. 


I’m going to walk you through the way I responded to this information, and let’s see where it takes us, shall we? 


Brain (FULL PANIC MODE ON): That’s a lot of deaths! What’s going on?!! Why are all these people dying  in Norway?! I need to call my nursing homes and make sure nobody is dead!! What if I have been telling people bad information?! What if I’m a bad scientist and a worse doctor?! 


My brain is very excitable. It is also basically programmed for threat avoidance, because our brains are supposed to keep us alive, so it’s better in general if they’re a little paranoid (especially if you’re living in a world full of unpredictable things actively trying to kill you, as humans have done for much of our history). But that means that sometimes we have to take a moment, let the initial shock and awe wear off, and take another look at what we’re seeing. 


So let’s take a look, now that my brain has stopped running in panicked circles and screaming, shall we? 


Step 1: How reliable is the source of my information? 


I had the same general headline from multiple news sources, which is usually (but not always) a positive sign of reliability, and so I walked it back to a medical journal that I trust for confirmation. 


The data itself comes from Norway – which has a centralized government-funded health care system, in which enrollment is automatic. Citizens have the option to purchase private insurance, but only about 10% of the population has done so. The relationship between the Norwegian government and the citizens of Norway is generally good. This means that they have ready access to certain health data through national registries, and the information we are being given is likely to be reliable. 


Step 2: What are the actual facts being reported? 


BMJ reports upwards of 20,000 doses of Pfizer’s vaccine were administered in Norway in the last few weeks and 23 deaths were reported in frail elderly patients “shortly after” receiving the vaccine. 13 of those deaths have been investigated — and it was felt in those cases that vaccination responses may have contributed to the deaths. The article also notes that around 400 deaths a week occur in care homes in Norway on a normal basis.


We are not given a clear definition of “frail” or “elderly”, although both of those terms are kind of a “we know it when we see it” thing for doctors. We also are not given any information about whether the reported deaths are more than the usual number expected. Remember — Norway is monitoring its citizens’ health just as closely as the US is (maybe more closely) and so it’s expected that medical personnel should report EVERYTHING so that the data scientists can sort it out. 


Step 3: What is the relationship between the facts? 


There is a potential correlation between administration of the vaccine and death in frail elderly patients. That means that it’s possible that these two numbers are going to move together:  if more frail elderly patients are vaccinated, then more of them will die shortly after the vaccination at a rate of about 10 deaths per 10,000 doses administered. It’s also possible that these two numbers have nothing in common, and as more frail elderly patients are vaccinated, more of them do very well. 


There is also concern for causation: in the patients whose deaths have been investigated thus far, it’s possible that vaccine responses may have been a factor in their deaths. That’s certainly a point of concern, and one that I’m going to be following for more information on.. 


Step 4: What other information do I already have that is important to consider? 


Pfizer did present data on safety in patients who were age 80 and up — but as widespread vaccination programs take place, we have rapidly exceeded the number of people enrolled in clinical trials. That means that instead of 73,000 data points (Pfizer enrolled 43,000 people and Moderna enrolled 30,000 people in Phase 3) we have over 12 million in the US alone. 


The more data we have, the smaller our p value gets, and that means that we can be more confident when we say that a particular reaction is (or is not) likely to be related to vaccination.


I take care of frail elderly patients in care homes on a regular basis. I worry about things like fevers, not eating well, vomiting, and diarrhea in those patients. They don’t have a lot of extra reserve — so when they get dehydrated, low on electrolytes, or hypoglycemic (low on blood sugar), that can be a really serious event that they may not be able to recover from. So I can certainly understand from a medical standpoint where enthusiastic vaccine responses (the kind that sent my otherwise-healthy colleagues home from work for a day) might have a devastating effect on someone without that reserve. 


Step 5: What am I going to do with all this information?


I’m not going to let my brain tell me to panic. Panicking does not help me be a better doctor, and it does not help me provide better information to my patients. 


I AM going to flag this topic in my mind as something that I want to continue to learn more about — I expect more data to come out as scientists and doctors across the world continue to observe and report what they are seeing, and I want to know what the data says. Because this is important. 


I AM going to use the information I have to inform my discussions with frail elderly patients and their families. It’s going to be important to talk about the possibility of an enthusiastic vaccine response and what that means, as well as to talk about what their risk of catching COVID-19 is and what that means. I can’t make a decision about vaccination for my patients and their families; my job is to be the best resource that I can be for them, and to help them make the best decision they can for themselves — and that decision may be different from one patient to another. 


Step 6: Keep learning. 


Never stop learning. Never stop asking questions. 

And don’t be afraid to say “I don’t know, but I’ll find out.”





I am a process nerd.

I had a migraine this morning, but I am prepared to blame it on a combination of staying up until 1 AM playing Dungeons and Dragons and waking up to snow all over the ground this morning. From a vaccine standpoint, I have no complaints. 


In case you missed my Wednesday midday post, Indiana has opened their vaccination program to ages 70 and up! The Department of Health was not quite prepared, I think, for the number of registrations they received: my news alert at noon on Thursday reported that more than 250,000 Hoosiers ages 70 and older had already scheduled appointments, and many people are reporting long wait times through the 211 helpline. That’s exciting news but also highlights the immense amount of coordination and infrastructure support that is needed to perform mass vaccination (something your public health departments help to coordinate on an annual basis in flu vaccine season). 

A little talk about vaccine storage 

The CDC has updated their current recommendations for vaccination to include people ages 65 and over as well as those under 65 with high-risk health conditions, but some parts of the country hospitals and health systems are still struggling to get enough supply to vaccinate their workers – while in other systems, calls are going out at the end of the day to avoid wasting already-drawn vaccine doses due to no-shows or appointments being left unscheduled. That’s a problem. 


There are a lot of factors that play into the supply and demand equation here, and supply-chain logistics is not something that I’m prepared to write a blog post at this time (also: that discussion is Fraught with complexity beyond my skill level). I’m also not prepared at this time to engage with the larger discussion of “who should get vaccines first,” because that is also Fraught. But one of the aspects I am prepared to talk about is the delicate timeframe we’re playing with here, and why we can’t just put the syringes back in the refrigerator for tomorrow. 


Remember, both of the current vaccines are mRNA vaccines, and RNA is very fragile. Both Pfizer and Moderna have wrapped that RNA up in lipid nanoparticles (that’s little fat bubbles, for those of you playing the ‘plain English’ game), and in order to keep the whole thing from just falling apart into a tiny greasy mess it has to be kept super cold. 


Pfizer’s vaccine is the fiddliest: it’s good in an ultracold freezer (-70°C/-94°F) for 6 months, on dry ice (replaced every 5 days) for a month, and in a hospital refrigerator for 5 days. Moderna’s vaccine is much easier to store – it can stay in a regular freezer until its expiration date, instead of Pfizer’s ultracold one, and lasts thawed for 30 days in a hospital refrigerator. For both vaccines, once the vial is punctured and you mix it for administration (at room temperature) it’s good for six hours.  You can’t go backwards – once the seal is broken those doses have six hours to be given or they’re lost as the mRNA degrades. 


That’s a problem, and one there really isn’t a good way to solve other than keeping those “call lists” and reminding people to hang on to their vaccine appointments. These vaccines just aren’t built to sit around, and Pfizer’s candidate especially requires a special ultracold freezer to store it. That’s a huge investment — and when we start talking about hardware requirements to distribute a vaccine, we start talking about disparities of distribution (which is another post in itself).


There’s a new kid strolling casually onto the block, though: Johnson and Johnson (referred to as J&J for the rest of this post) have announced some preliminary results of their phase 1/2a studies just this Wednesday, and they are seeing neutralizing antibodies in 90% of recipients at day 29 after the vaccine, with 100% of recipients showing neutralizing antibodies at day 57 and antibodies lasting to day 71 (that’s the last day they took data before publishing). This one-shot adenoviral vector vaccine is probably going to be stable in a regular freezer (-20°C/-4°F) for 2 years and refrigerated for more than 3 months. 


Let’s break down the science talk on that, shall we? 


I talked in an earlier post about how an mRNA vaccine works (10-second recap: mRNA is a set of instructions for your cells to print their own Wanted posters with the image of a particular part of the coronavirus spike protein), and that’s how both Pfizer and Moderna vaccines work. The J&J candidate is an adenoviral vaccine instead. It’s built on the technology that J&J (operating as Janssen Pharmaceuticals, their R&D arm) used to produce their Ebola vaccine, which has been in development since 2014 and was approved in Europe earlier this year. 


Adenovirus vaccines use an actual virus that has been heavily modified so that it can no longer use humans to make a zillion copies of itself (remind me sometime and I’ll talk about the crazy things that viruses do inside your cells). The adenovirus itself is just a string of DNA wrapped in a package of proteins called a capsid, which is the part the immune system sees. Human immune systems are equipped to produce a robust response to adenoviruses in general. As a viral researcher, that means I can stick some easily-recognized parts of the virus I *actually* want the immune system to destroy into the capsid, and count on your immune system going bananas about it. 


Specifically, the participants in J&J’s trial are showing the development of neutralizing antibodies in every participant within 2 months after a single shot. Neutralizing antibodies are the blockers of your immune system. They grab onto viruses and prevent them from infecting cells in the first place, so this is a genuinely promising result from technology that’s been under development for quite a while and has already been successfully used in another vaccine.  


This data is also just the Phase 1/2a preliminary data, which is a great excuse to talk about how clinical trials work, the importance of blinding, and why things seem to be moving so very swiftly these days!

What’s up with the speed of vaccine trials and the Emergency Use Authorization? Can I really trust this information? Everything is happening so fast! 

The short answer is: we have rearranged the way trials are structured and allowed for a temporary authorization based on the data that’s available at this point; all of this is still being studied so it’s important to participate in post-vaccine monitoring. 




Traditionally, when you have a new therapy (a drug, a vaccine, or some cool intervention) that you think will be effective for treating a disease, you perform human trials (after all the preliminaries) in four phases. Each phase is independently structured, and researchers fully complete one phase before moving on to the next. 


Phase 1: Safety. A small group of volunteers who understand that the thing you are doing to them is hopefully-but-not-definitely safe are given gradually increasing doses of your drug-or-vaccine. Samples are taken to look at blood levels, where appropriate. Participants are closely monitored for toxicity. The goal of Phase 1 trials is to answer the question “What is a safe dose range for this drug?” 


Phase 2: Efficacy. A larger group of volunteers are divided into a “control” and several “interventional” arms. The control volunteers are given a placebo (in medication trials, this is a sugar pill; in vaccine trials it can be a saline solution), while the interventional volunteers are given  possibly-but-not-definitely effective doses. The goal of Phase 2 trials is to answer two questions: “How much drug should be given?” (Phase 2a) and “Does this drug work at all?” (Phase 2b).


This is where J&J have currently stopped. They’ve released the results of phase 1 (safe dose range) for and 2a (effective dose) for all trial participants, but they are still doing some data analysis in their 65+ participants. That’s expected at the end of January. The conclusions drawn from the data we have available from the trial at this point are: 

  1. This vaccine appears to be safe  
  2. The dose used appears to be effective at inducing an immune response. 

We are pretty sure that – given the antibodies being measured – the vaccine will be effective, but we can’t say that for sure because that data hasn’t been released. That’s the Phase 2b question.


One of the ways vaccine manufacturers have saved time is by combining phases 1 and 2 or phases 2 and 3, depending on the information that’s already available.  That means they’re running multiple studies simultaneously based on “best guess” numbers (J&J is actually still collecting data on whether a 2 dose series will be better than a 1 dose protocol, for example). That saves time. 


Once Phase 2a and 2b are completed, trials move into Phase 3, which is the large clinical trial phase. In medication trials, the experimental medication is compared to existing therapies; in the coronavirus vaccine trials the experimental vaccine is compared to a saline injection (because there is no existing therapy). Again, the experimenters and the participants are “blinded” — who gets the treatment and who gets the placebo is kept secret — because this phase is designed to answer the question “What can we expect in the real world?”


This is the part where the statisticians get involved, because things happen in the placebo arm of a trial too. People in both arms of a phase 3 clinical trial are still people, and they are still going about their daily lives, with a range of experiences that affect their health and well-being. In a well-designed trial, your statistician has suggested enrollment numbers that should help your trial take all of these things into consideration. Your statistician has also helped you set an interim analysis point (more on this in a minute).  


People who are enrolled in a clinical trial are being monitored for any and every side effect they choose to report. They are also being monitored for evidence of the *endpoints* of the trial (in the coronavirus vaccine trials, this has generally been “did you get symptomatic COVID-19?”) Those reports are then handed to statisticians, whose job is to break down the reports and answer two questions: “Did this event happen *a meaningful number of times* more often in the intervention arm than the placebo arm?” and “Did this intervention accomplish the goal *in a meaningful way*?”


We have computers to help with those analyses, thankfully. Even more thankfully, we have statisticians who are trained to select the right analysis for the problem, because even though math itself is pretty cut and dried, choosing the math you do can make a dramatic difference in the appearance of the final results. 


Phase 3 clinical trials traditionally last for quite a long time! Because of this, researchers can set an interim analysis point in their trials: This is a point where they can step back, take a look at the data, and decide if the information they have is *overwhelmingly* in favor of the intervention they’re testing. In that case, they may decide to stop the trial early (so everyone can get the benefit of the intervention) and continue analyzing data in Phase 4 (the part where we continue to collect data after a drug or intervention is released to the market). 


That’s what happened with the Pfizer and Moderna trials, and what J&J hopes will happen in their trial: the interim analysis showed an overwhelming benefit in favor of vaccination (with regard to symptomatic coronavirus infection) and so the decision to move for Emergency Use Authorization was made. It means that we don’t have as much data as we normally do from a clinical trial, though, so it’s a decision that should not be made lightly. It’s also a decision that ideally is made based on pre-established criteria (remember when I said it was super important that the trial protocols were made public in advance?) so that the decision is not influenced by the hopes of the researchers.


We all have skin in the game when we do something; one of the hardest things to do is to admit that the medication you have worked so hard to develop does not do the thing you wanted it to do — or that it has side effects that are unacceptable and so won’t ever be useful. It’s important for scientists (who are regular people, after all) to build safeguards into their trials to help prevent this bias from slipping in and affecting their decision-making. 


It’s also important to have someone else review the data – preferably someone who is invested in the field and so is familiar with the general shape of the terms you’re going to be throwing around (nothing gets in the way of critically analyzing a paper by having to go look up what “in S-specific CD4+ Th1 and Th2 cells and in CD8+ T cells” means) – to look for issues with the study design, the statistical analysis, and the conclusions that you’ve drawn. It turns out that double-checking your work is super important! 


The process of double-checking scientific work is called peer review. In general, the medical journals that doctors rely on for their scientific information are referred to as peer-reviewed publications, meaning that any paper submitted to that journal goes through a peer review process before it can be published. It adds a layer of extra trust to the results of the paper — but it is not foolproof, and journals have been known to retract papers if it turns out the information they contain is inaccurate or misrepresented.


The Emergency Use Authorization (EUA) is another peer-review tool that allows the rapid-but-provisional approval of a drug, device, or intervention. Normally, the FDA review process takes about 10 months, as the agency reviews all of the available information and independently evaluates the benefit the new drug will bring to medicine, as well as the risks it may pose. Under the EUA process (as we’ve seen) that 10 month timeline can be shortened to “days-to-weeks”. A product that is being submitted for EUA is generally something that is urgently needed and has relatively strong information supporting its safety and effectiveness. 


Because EUA approvals are based on a rapid review of early data, the manufacturers are required to provide ongoing updates regarding their continued study of the intervention. In the case of the coronavirus vaccines, the FDA has required a minimum of 2 months of data on safety following the final dose in the vaccine series, which is a much shorter followup interval than we normally see in a vaccine trial, and continued updates on their trial data over the next several years.


An EUA is a temporary authorization only; ultimately the vaccines that we are seeing will need to undergo a full review and obtain FDA approval, but their manufacturers will need to produce long-term data in order to obtain that approval. In the case of the coronavirus vaccines, the FDA has required a minimum of 2 months of data on safety following the final dose in the vaccine series, which is a much shorter followup interval than we normally see in a vaccine trial, and even the best physicists have not yet figured out how to manipulate time to get two years’ worth of safety data into two months. 


Are you still with me? We’re into the home stretch. 


Normally, once an intervention has completed 3 phases of trials and undergone full FDA approval, the drug companies begin manufacturing plans. In this case, manufacturers began ramping up to full-scale production of their vaccines in July, at the beginning of Phase 3 testing. That allowed Pfizer and Moderna to have doses of their vaccines ready to roll the day they were approved — but put them at significant financial risk if the trials were not successful. 


So a lot of moving parts have been collapsed, abbreviated, combined, and restructured to allow this ultra-rapid timeline to proceed. When this happens, it requires everyone involved to be extra diligent about what they’re doing, how they’re analyzing it, and how they interpret the conclusions. 


In the case of the coronavirus vaccine, the data we have appears solid, the endpoints and interim analyses were determined in advance, and the conclusions are supported by the data. That’s good.  But the information we have right now is NOT final, and that is important to remember. The vaccine manufacturers have not closed their trials — they will be continuing to monitor trial participants for the next 2 years — and it’s important for people who are being vaccinated to participate in reporting their own experiences with the vaccine. 


The more data we collect, the more we know. And the better our answers will be. 






Babies are some of my favorite patients

My arm only hurts if I push right where I got my jab (what a delightful term). I made it through a topsy-turvy clinic schedule without excessive fatigue, and I currently have nothing to complain about to the nice folks at V-safe who sent me my daily reminder text to find out how I was doing. 


I also do not have any new super powers, unless you count filling the dishwasher without being asked to (I am a terrible housemate).

Can I (should I) get the coronavirus vaccine while pregnant or breastfeeding?


Short answer: It depends. 


Long answer: 

Let’s talk a little bit about how mRNA vaccines work so that we’re all on the same page with regard the science of vaccines, because I think that helps answer the question. There are, after all, some vaccines that you are NOT currently recommended to get while pregnant (MMR, Varicella, Live influenza, Zostavax; HPV, Meningococcal B) so the question with a new vaccine is certainly relevant.


Vaccines work by introducing your body to an antigen (A recognizable part of the thing we are protecting against) in some sort of low threat way. Bodies are excellent at recognizing things that do not belong — and not only do they seek and destroy, but they create specific antigen binding molecules called antibodies, as well as engaging your T and B the memory cells to remember, locate, and inactivate that particular antigen should ever be encountered again. There are no three strikes rules in your immune system.


One of the first widespread vaccines in the Western world was the smallpox vaccine. The process of smallpox vaccination (ask anyone who was a vaccinated child prior to 1972 about their scar) involves scratching a hole in the skin and introducing a close cousin to smallpox called cowpox into the hole. Cowpox is much less deadly than smallpox, and vaccinating with cowpox dramatically reduced the attack rate of smallpox, which is a disease that now has the dubious distinction of existing only in the laboratory. 


We still use live virus in some vaccines today. The MMR, Varicella, live inactivated influenza, and Zostavax (old shingles) vaccines use a live inactivated virus – real viruses that have been in some way altered to make them slow and sluggish; easy prey for a nimble immune system. However, as any pregnant person can tell you, pregnancy makes everything in the body go haywire – including the immune system. So we don’t give live virus vaccines to pregnant people (or people with heavily suppressed immune systems) because of the risk that the virus could pose to parent or baby if it proved to be too quick on its feet. 


The majority of vaccines today don’t use whole live virus, inactivated or not, because we’ve learned a lot of more predictable ways to present antigens to our cells. I’ll save the lecture on vaccine subtypes, but mRNA vaccines are a whole new way of presenting antigens from a public health standpoint. 


And that’s a big part of the anxiety around these vaccines, right? This is all new technology, after all. 

Except that it isn’t. In the oncology research labs, where some really amazing scientists keep trying to find better ways to treat cancer, mRNA vaccine technology has been under development for more than a decade. It’s not, actually, all that new. It’s just never been used for -this- type of vaccine before.


Your cells contain vast lengths of DNA – the instructions for making the proteins that make you –  folded up into those infamous double helices and stashed in the nucleus in tightly knotted chromosomes. In order to make a protein, a lot of complicated biology happens to make a copy of the relevant section of DNA, using a strip of bases known as mRNA. That’s short for messenger RNA, which is exactly what it does: mRNA takes the instructions from the DNA and carries them into the ribosomes, where it’s used as the blueprint for assembling amino acids into a protein. 


Enter the mRNA vaccine. When you are injected with an mRNA coronavirus vaccine, your body is handed a whole bunch of little instruction manuals for making an easily recognizable part of the coronavirus spike protein. Because RNA looks like RNA no matter where it came from, your cells pick it up and hand it over to the ribosomes. The ribosomes do their thing, and voila! Your cells have made a viral antigen. It’s recognizable by your body as Definitely Not Me, and so your immune system gets to work recognizing, remembering, and neutralizing. There’s no actual coronavirus involved in the administration, and nobody has to get scratched with a stick and rubbed with cowpox. 


Still with me? That was a lot of immunology. 


Back to our pregnant-and-nursing people who are still waiting for me to explain what all of this has to do with them, then, and I’ll explain. 


There are two types of vaccines that we don’t recommend giving during pregnancy: live inactivated ones (because your immune system is being deliberately suppressed by your body in order to avoid letting it notice that you’re growing a person who is about half Definitely Not You, and so we don’t trust it to catch the live virus in a safe and efficient manner), and vaccines for which we don’t have enough safety data to make a call yet, but where delaying vaccination for nine to ten months is unlikely to pose a significant risk to the pregnant person. 


And that’s where it depends. 


You see, yellow fever is a highly contagious infectious disease in some parts of the world — and the only vaccine we have is a live inactivated one. But because the risk of dying from yellow fever is so high, the yellow fever vaccine is still recommended in pregnancy if you can’t avoid going to an area where you are at high risk of catching it. 


We don’t have enough data on either of the coronavirus vaccines in pregnancy (see yesterday’s post on the power of numbers) to make a clear statement about safety. The science says that there is nothing in the way the coronavirus vaccine works that would pose a threat to a developing infant (it’s just a set of instructions, after all) — but I don’t have an absolute answer to give you here. 


If you are pregnant and you get COVID-19, you are more likely than a nonpregnant person who’s otherwise just like you to have severe COVID-19 disease (including ICU admission and death). You are also at increased risk of preterm labor and delivery, and of having a cesarean section at that delivery. Those are notable concerns!


Being vaccinated in late pregnancy may allow your body to pass antibodies across the placenta to protect your baby, as well. That’s why we give pregnant people a Tdap vaccine at 28 weeks – to help protect babies from whooping cough through what we call passive immunity. The body is designed to pass antibodies through the placenta to a growing baby, in order to help protect that baby against things that its immune system is likely to encounter. Developing passive immunity through vaccinating pregnant people has not been tested with coronavirus vaccines, but it’s likely that it will happen to some degree. 


If you are pregnant and eligible for the vaccine, you should talk to your doctor about being vaccinated so that you can make the best decision based on the data available. If your risk of exposure to COVID-19 is high, then you and your doctor may decide that getting vaccinated is the safest course. If your risk of exposure is low, then maybe you will make a different decision. 


What if I want to get pregnant soon?


There’s no reason that we know of to avoid being vaccinated if you’re planning to get pregnant. We aren’t aware of any effects on fertility related to the vaccine — and the spike protein is pretty unique. Remember, we are teaching your body to recognize a single part of the coronavirus itself – so if there were concerns about fertility related to coronavirus immunity, we would be quite likely to see them in people who had recovered from COVID-19. 


What about breastfeeding babies?


mRNA is very fragile. It’s designed to run a set of instructions from one part of a cell to another and then be recycled. Remember all those amazing ultra-cold freezers that the Pfizer vaccine required? That’s because mRNA breaks down very quickly at room temperatures. The vaccine itself is unlikely to make it to your baby through breast milk — but if some of it did survive that long, then being doused in hydrochloric acid in the baby’s stomach will finish it off. 


What we know is that antibodies are expressed in breast milk and are another source of protection from infection for a growing baby. Being vaccinated while breastfeeding is likely to provide some passive immunity for your baby, and is unlikely to cause any harm to them. However, some people are very sensitive to illness, and because they may feel poorly for a day or so (I hope everyone’s vaccine experience is as flawless as mine!), that may affect their ability to breastfeed (it’s still safe, but nursing a baby when you feel like dirt is No Fun) or to maintain milk supply (stay hydrated!!!) through those days. It may take extra effort to make sure breastfeeding the baby continues without interruption.


There are trials being started now (in animals) looking at reproductive safety specifically, so if more data emerges, I will try to update!





a vaccination clinic directional sign

A little break

It was Christmas, and I had a birthday, and then we had a new year’s holiday and I had a couple of days out of the office. I still don’t have any superpowers, but I did get to spend time binge watching The Muppet Show with my kids, so I am counting Parenting as another one of my everyday superpowers that I continue to manifest. 


Without intending to, that was a whole two weeks where I didn’t update and – as I mentioned – I received my second vaccine yesterday. I will strive to be a little more consistent in the next week or two. 


We’ve seen some news reports lately about severe reactions to coronavirus vaccines. In addition to the reporting system we have always used for severe vaccine reactions, the CDC has rolled out a smartphone-based monitoring system called V-Safe specifically for tracking the health of people who’ve received the coronavirus vaccine. 


A recent review of the adverse event reports for a 10 day period in December showed 1.9 million doses delivered (exciting!) and a little under 4,400 reports of “adverse events” (things we’re concerned about).  About 175 of those events were of concern as possibly being severe allergic reactions, and about 21 of those  events appeared to be true anaphylaxis (a life-threatening allergic reaction that overwhelms your body). That works out to about 11 cases of anaphylaxis per million doses – definitely more than the flu shot (1.35 per million), which is why our current practice is to give the vaccine in a clinic that is equipped to identify and treat anaphylaxis. 


At regular intervals, V-safe texts me a little survey to find out how I’m feeling, if I have developed any new concerns, or if I have gotten pregnant in the interim (nope). It also sent me a reminder to get my second dose. If you’re getting vaccinated (or have been already) and are not signed up, I’d encourage you to get registered! 


I will tell you the same thing I told V-safe: I feel good, but my arm hurt a little earlier today. It started about 18 hours out but at this point in the evening I really am not having any symptoms at all. I will also tell you that I have colleagues who have complained of fever, headache, and generalized yuckiness as far as 2 days out from their second dose, so I’ll continue to watch. 


(To give another perspective on risk — although you can’t make a direct comparison — today’s numbers in Indiana show 558,560 individual Hoosiers have tested positive for coronavirus and 8,595 Hoosiers have died of COVID. That is about 15,000 deaths per million cases.)


Science continues to move at a rapid rate, and recommendations continue to be updated as we are looking at balancing availability of vaccines with people who need to receive it, as well as looking at the reports of people who have received the vaccine. Since I last posted, the recommendations regarding people who have already had coronavirus have evolved.  CDC’s current recommendation is that if you have had coronavirus within the last 90 days you may choose to wait to receive your vaccine. If you received monoclonal antibodies or convalescent plasma (you should know who you are but if your sick days are hazy your doctor will know) then you definitely should wait 90 days (and discuss with your doctor the best timing for being vaccinated).  


We are seeing at least anecdotally some degree of more robust vaccine reactions in people who have already had COVID (in plain English:  If you already had coronavirus, your body is already somewhat primed to recognize and respond to the vaccine, and so it may be more likely that you are going to have a day or two where you feel yucky). It makes sense, if you already have protective antibodies, that you can choose to wait a few months — your immunity is not likely to fade that fast. 


However, if you received monoclonal antibodies (that’s an outpatient infusion that ends in MAB), what we are giving you in that infusion is literally a cocktail of antibodies. These are designed to augment your body’s response, targeting and inactivating the virus and limiting its ability to continue to spread through your body.  There’s a similar idea behind convalescent plasma (that’s an inpatient infusion given in some centers to specific patients), except instead of laboratory-grown antibodies, the plasma is extracted from people who have already recovered from COVID-19. 


Bodies are not so smart sometimes: your body assumes those antibodies are home-grown – and so, when you receive your vaccine, you may not make quite as many antibodies of your own if you have a whole bunch of artificial ones floating around already.  That’s why we recommend you wait. 


I had a little list of questions and thoughts to cover before I took an accidental vacation. I suspect they’re still relevant. 

If I have asthma or epilepsy, should I take any precautions regarding this vaccine?


As far as we know, the coronavirus vaccine does not show any increased risks for people who have asthma or epilepsy. However, it’s important to remember that these diseases, like many diseases, have a wide spectrum of severity. We know that some people who have epilepsy show an increased risk of seizures if they have a fever, are under physical or emotional stress, or when they are even mildly ill, and so if you are one of those people you should definitely talk to your doctor about their recommendations. Similarly, if your asthma tends to flare up when you are under stress or not feeling well, you should check in with your doctor.

What if you were tested for antibodies after your COVID-19 illness and were negative? 

Short answer: OK to be vaccinated, although you could certainly consider waiting for 90 days after your recovery.


Long answer: 

There’s more to immunity than antibodies. Your immune system also has “memory cells” whose job it is to be ready to recognize a specific antigen (remember, an antigen is anything your immune system recognizes as “not me”) and produce antibodies rapidly.  We don’t completely understand how B and T memory cells are formed and do their jobs, and we don’t have easy tests to measure the efficacy of those cells, but we know that they can last for decades. That’s where the real staying power of vaccines comes in: they activate the memory cells of the body. In fact, there’s some evidence that your memory T cells are activated proportionately to your vaccine response, so those of you who get a hefty reaction to the coronavirus vaccine can take comfort in knowing you’re building immune memory for decades to come. 


Should COVID long-haulers have any special considerations?


At this point in the pandemic, we recognize what’s called “long haul COVID” as symptoms that develop during or after COVID-19 infection, continue for ≥12 weeks, and cannot be explained by an alternate diagnosis. 


Let’s break that down, shall we? It is at this point considered the normal clinical course of COVID-19 to have symptoms for up to 3 months following your diagnosis. Studies suggest at least 1 in 10 (and up to ¾ or more) of symptomatic people will have some lingering symptoms for 6 weeks to 3 months after COVID, and while fatigue is the most common complaint, we are also seeing significant numbers of patients experiencing shortness of breath, chest pain, cough, memory problems, concentration issues, anxiety, depression, and PTSD. My clinical experience — what I’m hearing and seeing in my own patients — tells me this is right on the money.  COVID is no joke. 


Long haul COVID patients are experiencing some portion of these symptoms for more than 3 months. As doctors, we are in the business of helping people, but we have very few effective treatments for these symptoms, and so treatment mostly consists of trying to find something that’s measurably wrong (lung damage, heart muscle damage, blood clots, things like that) so we can target therapy. 


The good news is that none of this seems to impact your ability to get the coronavirus vaccine. Your immune system may have been complicit in the processes that got you there (we don’t completely understand why people are affected so differently, but immune system responses likely play a part), but it’s unlikely to turn traitor with regard to the vaccine. 


Now I think I’m caught up with questions.