Worries about COVID vaccines and infertility are ridiculous

Public Service Announcement: Claims that the COVID vaccine could cause infertility are somewhere between misguided and malicious. There is no more reason to think that COVID vaccines can cause infertility than that they could cause diabetes, or heart attacks, or arthritis, or irritable bowel sydrome, or anything else.

Vaccines are not entirely irrelevant to pregnancy. As a general rule, pregnant women are advised against vaccines that consist of a live attenuated virus or bacteria, out of abundance of caution. The the MMR (measles, mumps, rubella) vaccine stands out as one example. However, women are sometimes vaccinated before they know that they are pregnant and, fortunately, adverse effects on the fetus have not been demonstrated. Thus, the risk to pregnancy seems to be more theoretical than real. (And just for clarity, COVID vaccines do not contain live attenuated virus.)

Pregnancy aside, in the history of vaccination there have been a few vaccines that were pulled from the market due to safety problems. In the 1960s, an RSV vaccine for children was found to actually exacerbate disease [1]. In the late 1990s a vaccine against rotavirus was pulled after it was associated with a small risk of intestinal intussusception (where a segment of the intestine folds back on itself). Other vaccines have special safety considerations. The live polio vaccine, for example, is no longer used in countries with low polio risk because the virus can sometimes revert to virulence due to mutation in its genome [2]. As another example, the smallpox vaccine is still used in certain laboratory situations even though smallpox has been eradicated [3]. However, skin conditions like eczema and psoriasis pose a safety risk for this particular vaccine. The kinds of issues that I have described are well known among vaccine researchers and clinicians.

It is one thing to worry about how a live vaccine might theoretically affect a fetus, which doesn't have a functioning immune system. Similarly, I can understand being cautious when there are no safety data on pregnancy. But I cannot think of any vaccine used in the U.S. or internationally that is even suspected of causing infertility. It just isn't a thing.

There certainly are infectious diseases that can cause infertility, which leads me to a question: Why would you be more worried about a vaccine causing infertility than about the disease itself? It makes no sense. But that's probably because it isn't supposed to make sense; it's just supposed to scare.

Notes:
1. That a vaccine could make a disease worse is counter-intuitive at first glance, but there are exceptions to most rules in biology.
2. The live polio vaccine is superior to the killed vaccine in several respects, which is why it is still used in certain geographies where health infrastructure is poor.
3. It's not because they are doing smallpox research. It's because the virus that was used as the smallpox vaccine--called vaccinia--is a useful laboratory tool. Inadvertant infections can be nasty, so lab workers may be vaccinated as a precaution.

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Vaccination: What If I Already Had COVID?

Current recommendations are that people who had COVID should still get vaccinated. Does it do any good? In looking into this, I found two recently published papers (there may, of course, be others) that address this question with interesting results [1].

First, yes, the first dose of the mRNA vaccines significantly boosted the level of antibodies of people who previously had COVID. But interestingly, the second dose didn't seem to add much additional benefit.

At the same time, systemic reactions (fever, chills, fatigue, et.) to the first dose were more common in people who previously had COVID than in people with no prior exposure. Reactions to the second dose were similar irrespective of exposure history.

Does this mean that if you've already had COVID you can skip the second mRNA dose? Well, on average the data seem to point that way, although there will always be variability in the population. We don't know what the longer-term effects would be, like how long the antibody levels stay elevated. But if you previously had COVID and were miserable from the first mRNA dose, you might talk with your doctor and/or health department to see what they think.

I don't know whether or not recommendations will change based on these data. One problem is that people are often not reliable in recounting their health history. I know people who think they had COVID very early in 2020--so early that it is unlikely to be true. One person was convinced they had it in the fall of 2019! So if health officials said, "If you had COVID you only need one dose," there is a legitimate fear that we would end up with a bunch of half-vaccinated people because they self-diagnosed themselves as having had COVID. So I can't blame health officials if they just stick to two doses to help ensure everyone is fully vaccinated. But if you are really sure that you had COVID, then it might be a conversation worth having with your doctor and/or health department.

Notes:
1. Pre-print versions of these papers came out in February. However, official publication was within the last two weeks, and both can be viewed for free: here and here.

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Vaccine #2 Achieved

This week I received my second dose of the Pfizer COVID vaccine. Hooray! The next day was no big deal for me. I had some minor aching in my back and legs, and of course a sore shoulder, but if I had woken up with amnesia I wouldn't have had any reason to think that day was out of the ordinary (except for the shoulder, which was fine by the second day). Soon I will be considered fully vaccinated (i.e. second dose plus 10-14 days).

I'll be honest that things weren't as smooth for my wife. She started feeling increasingly ill the next day and developed a fever that got as high as 100.8 degrees F, along with a lot of aching (she said even her toes hurt) and chills. It hit hardest about 24 hrs after the vaccine, but after another 7 hrs the fever broke. On the second day she was feeling better, but still recovering from the soreness. By the third day she was pretty much fine [1].

It's impossible to know, but I can't help but wonder whether our respective responses to the second dose would have any correlation to severity of disease. If so, my wife would have been in pretty bad shape. Or, if it were an inverse correlation, I would have been in bad shape. Fortunately, we'll never know.

Some may think, "Well if I have a chance of getting sick with or without the vaccine, then why get the vaccine?" That's the wrong way to look at it. First of all there is the simple matter of duration. My wife was miserable for 1 day, and then it was over. People who get COVID are miserable for many days. Second, although my wife felt ill as a result of her immune system kicking into gear, there was no underlying disease. There was no virus causing damage to various organs, no loss of smell, no coughing, no extreme fatigue, and no breathlessness from simply going up the stairs. There was also no wondering when (or whether) recovery would come, worrying about whether a trip to the hospital would be needed, worrying about whether anyone else in the family would be next, or worrying about long-term effects. Other than some special cases, there is no rational risk assessment that would suggest that it's better (or neutral) to not get vaccinated.

We can't completely throw caution to the wind yet, since our 13-year-old is still vulnerable. But Pfizer has reported 100% efficacy in his age range, so I think it's probably only a matter of days before it is approved for him. At any rate, our family is close to being immune (our daughter was previously vaccinated due to some lucky circumstances--with no side effects), and I can soon go out to lunch with coworkers without worrying about getting sick myself or bringing the virus home to my family.

So my advice is to get vaccinated, but if you get the Moderna or Pfizer vaccines [2], just assume that you may need a sick day after the second dose. If your experience is more like mine, then great! But if your experience is more like my wife's, then at least you will be prepared.

Notes:
1. My wife had/has a bulging disk in her neck, so if she's not careful with her posture there is a domino cascade of muscle cramping in her upper back and a resulting headache. We think that the hunching and shivering set off that cascade, so technically on the third day she was still recovering from that.
2. I'm not as familiar with the Johnson & Johnson side effects. My wife's social media intelligence is that they are less severe, but last longer.

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Vaccine #1 Achieved

This week I received my first dose of the Pfizer COVID vaccine. Hooray! Right now, cells in my body have taken up the mRNA that was delivered by the vaccine and are producing the Spike protein of the coronavirus. Dendritic cells are starting to notice, and will make their way to lymph nodes to alert B cells and T cells that this foreign protein is in my body. Soon B cells that recognize the Spike protein will start to make antibodies--little proteins that bind onto the Spike protein whenever they come in contact with it.

In three weeks, I will receive my second dose, and the process will repeat except that the B cells that were activated the first time will really kick into high gear. At that point, my assimilation into the Bill Gates--Tony Fauci--George Soros conspiracy will be complete! (Also, I'll be immune to COVID.)

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How the New COVID Vaccines Compare to Other Viral Vaccines

The leading vaccines against SARS-CoV-2 are based on a new technology that delivers mRNA to cells. This novelty, combined with political and social division, has resulted in a fair amount of nonsense commentary about them. The AstraZeneca and Johnson & Johnson vaccines are also somewhat novel. I thought I would quickly put these new technologies into perspective by comparing them to other viral vaccine technologies.

The first thing you need to know is that the principal purpose of a genome is to store the sequence information for all kinds of different proteins. Our genome is made of DNA, but it does not directly make the proteins. Rather, a similar intermediate molecule called messenger RNA (mRNA) is produced from DNA, and it is the mRNA that is directly read by the cell's machinery to make proteins. DNA -> mRNA -> protein. (Additional variation on this scheme can be found among viruses, but RNA -> protein always holds.)

Next, the immune system can be conceptually divided into two arms that work together: innate and adaptive. The innate system responds in ways that are not specific to a pathogen (disease-causing microbe). It's what makes you feel lousy and gives you a fever, and it kicks in quick. The adaptive immune system takes longer to respond, but produces antibodies and other cells that specifically target a pathogen. The value of vaccines comes from their ability to engage the adaptive immune system such that it is ready to go when the actual pathogen shows up. When we talk about being immune to something, we're really talking about the adaptive immune response.

In order to gain immunity, the immune system needs to come in contact with components (usually proteins) of the pathogen. There are several ways of doing this. I've listed the basic strategies for viruses along with some well-known examples in human medicine. Almost all of them are also used in veterinary medicine. There are some further variations to these strategies, but I think this captures the major themes.

1. Infect someone with a weakened virus that does not cause disease. The virus commandeers the cells to produce viral proteins (via viral mRNAs). This is the oldest and classic strategy. (Examples: smallpox, measles, mumps, rubella, yellow fever, and oral polio.)

2. Inject a virulent virus that has been inactivated such that it cannot replicate. This is also a relatively old method. (Example: injected polio, hepatitis A)

3. Inject purified viral proteins. (Example: hepatitis B)

4. Inject virus-like particles (VLPs). These are essentially virus particles that do not have any genome, and thus no ability to replicate or produce more viral protein. (Example: HPV)

5. Use a different non-pathogenic virus as a Trojan horse to make proteins of the virus of interest. (Examples: the AstraZeneca and Johnson & Johnson COVID-19 vaccines are, I believe, the first approved human vaccines of this type. However, this strategy is used in a number of veterinary vaccines.)

6. Inject DNA that codes for viral proteins. DNA -> mRNA -> protein. (Doesn't seem to work well in humans, so it is not used in human vaccines. But there are a few examples in veterinary use.)

7. Inject mRNA that codes for viral proteins. This is the newest technology, first used by Moderna and Pfizer/BioNTech. The challenge of this method has been to deliver RNA to cells, since RNA is easily degraded. The technology advancement has been figuring out how to encapsulate the RNA in lipid nanoparticles such that the RNA is protected until it is delivered inside the cell.

In each of these cases, the adaptive immune system is exposed to viral proteins--proteins that were either produced by the body's cells, or were produced by cell culture prior to injection. mRNA vaccines are the cleanest vaccines in the sense that they don't involve any extraneous viral proteins or genetic material. They really get to the heart of the process: mRNA -> protein, and it's exciting to envision how they might be applied to other diseases.

Each method has pros and cons, and has to be matched to the biology of the virus and the resulting immune response. For example, in some cases antibodies directed against a single protein are sufficient to give you immunity. In other cases it's not that simple, so you wouldn't use a strategy that only delivers a single protein. But in every case, it really boils down to exposing the immune system to the right viral proteins in the right way.

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Four Years Ago: What I Got Right and Wrong About Trump

Four years ago today, on the first day of the new Trump administration, Sean Spicer called a press conference to tell lies about the size of the inauguration crowd. Here is what I then wrote:

What to Expect: A constant stream of this kind of thing, and four years of attacks on media, science, and any other sources and institutions that don't go along with his narrative of greatness, or that attempt to hold him accountable. You can especially expect him to project on others his own liabilities....

Here is my warning and plea: Do not give your mind over to his efforts to delegitimize truth. You can like his policies. You can think he's better than Hillary or Obama. Whatever. But make him earn your trust! Don't take anything his administration says at face value. [I'm grabbing you by the lapels]...don't let him (and his acolytes) control your perception of truth. You will regret it.

I think the only thing I got wrong is that not enough people regret it.

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I Was Told That Trump is Like Captain Moroni, Doesn't Seek Power

This is just a reminder that, days before the election, Sen. Mike Lee (R-UT) compared Donald Trump to Captain Moroni, asserting that he doesn't seek for power.

 “To my Mormon friends, my Latter-day Saint friends, think of him as Captain Moroni,” Lee said pointing to Trump. “He seeks not power, but to pull it down. He seeks not the praise of the world or the fake news, but he seeks the well-being and the peace of the American people.”

I expect to remind you again in two years.

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How to Tell that Someone is Full of Crap: A Short Guide

A non-exhaustive list of signs to watch for:

• When they say one thing in public, and another in court
  
• When they say that they are not obligated to tell the truth when they are not under oath
• When they insist on things that are denied by the 'hard news' side of their same network or newspaper
• When they make claims contradicted by their own official report
• When evidence and data take a back seat to feelings and anecdotes
  
• When they, as non-professionals, attack widely-held professional opinion--especially when it includes demonization of the professionals themselves
  
• When they widely proclaim that they are being oppressed and silenced (assuming they live in a free society)
  
• When there are no hard, disappointing truths; only corruption and conspiracy
• When they avoid introspection, never admit to being wrong about anything of substance, or fail to give any principled reasons for changing their mind
• When they say that evidence will be forthcoming--especially when they keep saying it
  
• When their primary concern is "controlling the narrative" or winning the debate
• When they invoke patriotism and religion to help sell their crap
  
• When they have a history of being full of crap
  
• When they are incentivized to be full of crap
• When they deny that crap is, in fact, crap

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