Why Anti-Viral Drugs are Hard to Come By

This post isn't specifically about hydroxychloroquine or ivermectin, but the craziness over using them as a treatment for COVID made me think that it might be worth a quick explanation as to why they, or any other known drug, are inherently unlikely to be anti-viral therapies.

Let's start with antibiotics--the medicine that you use to fight a bacterial infection. How do they work? Put simply, they work by screwing up the molecular processes of bacteria. They are small molecules that bind to or alter important bacterial enzymes. It's like throwing a wrench (spanner, for the British) into a machine, or a broom stick into the front wheel of a bike. Except, here we are talking about specific interactions between molecules because they have just the right shape and chemical properties. Antibiotics screw up the chemical processes that bacteria need to live and grow. The reason that antibiotics don't also screw YOU up is because bacterial enzymes are different enough from ours that they can be selectively targeted. You don't have peptidoglycan in your cell membrane, for example, and the ribosomes in your cells are a little different than those in bacteria. Thus, scientists have been able to find small chemicals that, at the right concentration, can kill bacteria and not you [1].  The same applies to parasites. This general concept is called selective toxicity.

So how come there aren't more anti-viral medicines? Why is it that a doctor will diagnose you with a virus and then usually say there's not much you can do but manage the symptoms? The answer is that selective toxicity is much harder to achieve with viruses. That is because viruses mostly commandeer your cellular machinery for their own purpose. They do use some of their own enzymes, but there aren't that many targets to go after. This is further complicated by the fact that there are dozens of viruses that can infect people, each with different enzymes, and even if you could find a small drug molecule to screw up that enzyme, the virus has a decent chance of evolving resistance. Also, you usually don't know that you are infected with a virus until you develop symptoms, and by then an anti-viral probably isn't going to do much for you anyway (unless it is a chronic infection). Simply put, it is hard to screw up a virus without screwing up your own cells too. That's just the science side of it; the economics of drug development are a whole additional dimension to the issue. So for the most part it is up to the immune system to deal with viruses, hence the importance of vaccination.

So the idea that some random drug that is good for something else would also just happen to specifically inhibit some part of the SARS-CoV-2 replication cycle is just inherently unlikely. Not impossible, but really unlikely. And just because something works in cell culture does not mean it will work in you. Cell culture is a starting point, not proof of efficacy!

But maybe we don't need the drug to specifically target the virus. Maybe it can just perturb some cellular process enough that the virus has a hard time reproducing while the immune system ramps up to take care of it. That's a theortical possibility, but if the drug isn't screwing up your cellular processes enough to cause you some really unpleasant side effects, then it probably isn't doing much of anything to stop the virus either.

In summary, unless approved by regulatory authorities, you should be very skeptical of claims that an existing drug also happens to be an anti-viral. The same goes for any kind of dietary supplement or non-FDA approved therapy. Remember, it takes chemcial sharpshooting to kill a virus without killing you. If you take a drug that isn't approved as an anti-viral, you are probably shooting the wrong target.

Notes
1. The drug, of course, has no idea what it is supposed to target. It just follows the laws of physics and chemistry.

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Time to Clean Up Some Vaccine Information Pollution

There is a viral video going around of a pathologist claiming that the COVID vaccines are toxic. It is a compeling talk, but it is garbage...in a sort of glorious way. Time for cleanup.

First, who is this guy? Dr. Ryan Cole is apparently an independent pathologist in Idaho who has previously attracted the attention of FactCheck.org, and has affiliated with a group called America's Frontline Doctors, which is a group of doctors with...let's say a contrarian take on COVID and public health. The video is of a presentation he apparently gave on July 27 to his like-minded colleagues.

Cole's basic claim seems to be that the Spike protein of the virus is responsible for most of the pathology and disease manifestations of COVID. Therefore, we should not be pushing vaccines that use the Spike protein on people, and especially children, since we don't know what the long-term effects will be. (As if we do know the long term effects of COVID infection?) Also, we should be doing more autopsies of people who die after having had the vaccine in order to determine whether there is a causal connection.

I've stated his thesis using calmer and more neutral language than Cole, and put this way it seems like a reasonable position. When watching the video, I quickly determined that this was a guy with an axe to grind. There's nothing wrong with being passionate, but the way that he derided the vaccines made it clear that this wasn't just a doctor with some scientific concerns. It was almost like he was trying to come up with his best insult. At one point he said, "these are not vaccines," which is kind of a stupid thing to say because they are, in fact, vaccines. (Maybe he has his own special definition?)

Before I address his claims, I need to do a spoiler alert. Just like knowing how a magic trick is done or how a mystery ends can take away the feeling of wonder, what I am about to explain may deny you the opportunity to feel the same sense of fear and indignation toward the vaccines and medical establishment that you might otherwise feel. So if you want to feel the tension build and wonder how it could possibly be resolved, go watch now and do not read further.

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OK, I'm going to do the big reveal up front, but we'll still go through the journey. Here it is: NONE of the scary pictures of inflammation that Cole shows are from a vaccine. Even worse, some of them are actually from COVID patients. You may find that hard to believe, but stay with me.

Inflammation
If you haven't watched it, much of the talk consists of Cole showing slides of tissues and commenting on the inflammation. You could be excused for thinking that these were from cases that he investigated or experiments that he did. In fact, at the 4:45 mark he says, "We did studies in lab animals." He must have meant the royal 'we' because there's no evidence, that I can find, that he has been involved with any animal studies dealing with COVID. None of the image slides contain references, but thanks to the magic of Google I was able to track them all down. They are all pulled from the scientific/medical literature, or from medical news articles.

I'm going to go through each of them and comment on his claims. Because I am lazy, I don't feel like reproducing all of the images here, so I'll just give a description, where in the talk they can be found, and provide links to the image sources so you can check them out for yourself.

1. (5:20) Endothelial cell mitochondria (black, purple, and rainbow colors) - Claim: The damage is caused by Spike alone from the vaccine, not the virus. Fact: This is wrong. No vaccine was involved. What the researchers did is to make inert viral particles that have the Spike protein and treated endothelial cells (in the lab) with these particles. Yes, they attributed the observed, effects to Spike, but it is a logical leap to say that the vaccine would do the same thing--or be biologically meaningful if it did. In fact, the article suggests that a vaccine would be protective.

2. (6:57) Lung tissue (the image appears to come from news articles, like this one, that describe results that were later published) - Claim: disease is from the vaccine. Fact: Again, no vaccine was involved in the study. The researchers injected part of the Spike protein directly into the trachea of mice. Perhaps it shouldn't be surprising that putting a foreign protein directly into the airway caused inflammation. It's an interesting finding that helps inform us about the disease process, but it's another logical leap to say that the vaccines would cause the same effect. More about this later, but for now the practical takeaway is don't snort Spike powder.

3. (8:16) Brain cells - Claim: inflammation from Spike. Fact: This comes from the autopsy of a man who had the first Pfizer dose but caught COVID 3 weeks later while at the hospital for other health problems. His death was ruled not to be due to COVID infection, since they did not see typical signs of COIVD, but many of the tissues sampled (including brain) had viral RNA and he was well past the point when Spike would have been present from the vaccine. At any rate, it's no surprise that having virus in the brain would lead to inflammation.

4. (8:28) Heart images, myocarditis (scroll down) - Claim: "That's after a shot." Fact: These images are from a public database of radiology images. The case description does not mention COVID or the vaccine. It's true that there are some rare cases of myocarditis associated with mRNA vaccination (but not the Johnson and Johnson vaccine), and it could be that this image is representative of such cases (I'm not qualified to say), but this image is not from someone who had a vaccine. Cole probably pulled it from an online news article that used it as a stock image (like this one) and mistakenly thought it was actually from a vaccine patient.

5. (8:55) Heart tissue - This image does not have anything to do with COVID at all. The top pictures are from an entirely different virus, enterovirus A71.

6. (9:50) Kidney - The rest of the images are shown in rapid succession and can be addressed together since they can all be found in the same article. Fact: All of these images are from people who actually had COVID.
7. (10:05) Liver
8. (10:15) Testes

If you are wondering why Cole would show tissue slides of people who had the disease (or even a different disease) and then claim that this is what the vaccine does, you're asking a good question! I think the most charitable answer I can give is that Cole has taken the data from the mice with Spike injected in their airway and extrapolated to the conclusion that all COVID inflammation comes from Spike and therefore the vaccines (which cause your cells to make Spike protein) cause pathology equivalent to COVID disease. That's quite the extrapolation! And it's plainly false just from a clinical perspective. (Are vaccinated people having to monitor their oxygen levels?) So if you follow Cole's logic, you should avoid the vaccines and instead leave yourself open to becoming infected and getting the types of pathology that he has shown in his slides. (Joke: maybe it's best that Cole's patients are already dead.)

Miscellaneous
The images are really the main story, but there are a variety of other claims and issues that need to be addressed.

First, let's go back to the mice that had Spike protein (actually only part of the Spike protein, S1) injected in their airway. Consulting the paper, the scientists gave the mice 400 micrograms of Spike per kg of the mouse weight. Cole mentioned a Harvard study that measured the circulation of Spike in the blood of people given the Moderna mRNA vaccine. Spike (S1) was only detectable for 9 days or so after the first shot, and virtually not at all after the second shot (consistent with the rise of antibodies). At the peak of S1 circulation, the average amount was 68 picograms/mL. Let's do some math. The Internet tells me that an average adult human has about 5 liters of blood. Let's make it 6 L, which is equal to 6,000 mL. 6,000 mL x 68 pg/mL = 408,000 pg = 0.408 micrograms total. Let's assume a weight of 90 kg (~198 lbs). Divide 0.408 micrograms by 90 kg = 0.0045 micrograms/kg. Do I need to continue in order to make the point that the mouse study used WAY more S1 protein than was found in the blood of vaccinated people?

(7:43) Spike crosses blood brain barrier (BBB). The slide accompanying this claim contains the only references provided in the whole presentation. Note that the slide title, "Spike as Toxin" comes from Cole, not the referenced articles (here and here). Poking around the literature, the focus seems to be on the ability of the virus to invade the central nervous system. I am unable to find any literature that addresses the BBB in the context of vaccination. However, I think you would be hard pressed to show that neurological outcomes of vaccinates are worse than COVID patients, and that's putting it lightly. Perhaps there's a kernal of truth here that could improve the next generation of COVID vaccines, in terms of tolerability or side effects. But that's just me trying to be charitable.

(10:30) Pfizer biodistribution study submitted to Japanese regulators shows accumulation in ovaries of rats, with a 16% decrease in fertility. Fact: First, the study shows that the percent of nanoparticle lipid that goes to the ovary is less than 0.1% of the dose, compared to the injection site (roughly 25%) or liver (~15%). As for the decrease in fertility, I was unable to find a source for this claim in the limited searching I did. But I DID find a recently published study from Pfizer showing that female rats given four doses of vaccine were not different in any way from non-vaccinated rats in terms of fertility, including estrous cycle.

(15:00) Cole makes a variety of claims about immune dysregulation leading to reactivation of other viruses and increase in cancer. These claims are purely anecdotal so they are difficult to address. He mentions a study from Germany and the Netherlands, but that's not much to go on. I suspect that, like his other examples, he is extrapolating data from COVID patients and inappropriately applying it to vaccinated people.

Finally, the CDC asked me to hide this from you, but I'm going to let you in on the secret if you promise not to tell. You can find information on COVID vaccine adverse events here and here, among other places.

Conclusion
I have shown that Dr. Cole's claims about vaccines are not connected to any of the images that he showed in his presentation, and that others of his claims are either false or missing important context. It is plainly dishonest to use images of tissues damaged by the virus in order to argue that the current vaccines are dangerous. I think it is reprehensible, and even unethical, that he would claim that vaccines are ruining the hearts of children, while showing a picture of a heart that was damaged for unrelated reasons. Never does he say that these are just examples of the kind of thing he is worried about. And it is worth stating again: following Cole's argument to its logical conclusion leads to the idea that people are better off facing the virus than being vaccinated. On a population level that is clearly false.

Buried in his screed are some questions and issues that perhaps have scientific merit, but he has overshadowed and distorted them with his sensationalism and misdirection. At a certain point we leave the domain of scientific debate and enter information pollution.

Now that you've taken all of this in, go back and watch the video again and see if it still has the same punch. Hopefully, my cleanup has been worthwhile.

P.S. I've tried to make sure my ducks are all in a row in this, but please bring any errors to my attention.

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The COVID Lab Leak Hypothesis

Humans abhore uncertaintly like nature abhores a vaccum. The exact origin of the SARS-CoV-2 virus that is responsible for the COVID pandemic is still a bit of a mystery, which leaves the issue open for lots of storytelling. And what makes for a better story: that the virus arose naturally, or that it was released from (and maybe engineered by) a Chinese lab? If I were making a movie, I know which plot I would use. However, my position is like that of a lot of scientists: that a lab leak is possible, but that a natural origin is more likely. It is nevertheless amusing how adamant some people are that the virus could not have just come from nature. The issue is a complicated one, but I think this article from FactCheck.org is a nice summary: The Facts – and Gaps – on the Origin of the Coronavirus

I just want to make a few additional comments. Some have asserted that the furin cleavage site in the Spike protein is evidence that the virus was engineered. More specifically, they point out that two arginine amino acids in a row are coded by the DNA sequence CGG. The FactCheck article addresses the CGG part (and if you want to dig in further, check out this archived Twitter thread), but I want to make something more explicit.

If you look at the figure of the furin cleavage site, you will see the DNA sequence of this region along with the amino acid translation. The insertion into the SARS-CoV-2 sequence is in red and underlined. Notice that the novel sequence appears to split apart the original serine codon, moving the A (green and italicized) to the end [1]. There doesn't seem to be any logical reason for this from a genetic engineering point of view. If you wanted to insert a DNA sequence to create those PRRA amino acids, you would most likely do it in a way that didn't disturb the surrounding codons, such as what I've shown on the bottom [2]. I'm not saying that this PROVES anything one way or another. I'm simply saying that this is a weird way to genetically engineer a furin site into the protein, and in my mind it cuts against the idea.

One further point not addressed in the article is the argument that the CGG-CGG sequence results in a restriction enzyme site (FauI) that could be useful in laboratory genetic manipulations. Since each arginine could be coded by any of 6 DNA codons, that means that there are 36 possible DNA sequences to code for RR. Isn't it suspicous that this one codes for the FauI site?

I took a look at all 36 possible combinations. To begin with, there are 2/36 ways to get a FauI site. So now we're down to 1/18 vs 1/36. But more importantly, I found that an additional 15 possible codon combinations resulted in the presence of a restriction enzyme site that was as good (or better) as FauI for the presumed laboratory manipulations [3]. In other words, that FauI site isn't so special after all because if all codon combinations were equally likely, it is roughly a flip of a coin as to whether a potentially useful restriction site would be created in the RR of the furin cleavage site. And that's not taking into account additional possibilites that could be created by different codons for the flanking P and A amino acids.

So for now I end where I started. I think it is most likely that SARS-CoV-2 was transmitted to humans in a natural chain of events, but a lab leak is theoretically possible and difficult to disprove. We may never know with absolute certainty.

Notes:
1. I say 'appears' because it might not be that straightforward. The A at the end of the new sequence isn't necessarily from the original serine.
2. To be clear, I'm not saying that you would expect that exact DNA or amino acid sequence if the furin site was a product of human engineering. I'm saying that it would be spliced in differently.
3. Since FauI is a 5-cutter (i.e. recognizes a sequence of 5 nucleotides), I only considered enzymes with a recognition site of at least 5 nucleotides.

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How To Get the Church's Stock Returns

And now for something different: Today my attention was drawn to news articles highlighting the Church's U.S. stock holdings (via Ensign Peak Advisors) [1]. To my eye, the articles have a bit of a sensational air to them, intended to impress (and perhaps anger [2]) people who don't pay attention to the stock market and/or have limited financial literacy. So I thought some added context was warranted [3]. Let's take a look.

Ensign bought GameStop in Q4 of 2020, turning $870,000 into about $8.7 million, a 900% gain. Wow, what a profit!

What is $8.7 million in proportion to the size of the portfolio? Answer: 0.019%. On a normal trading day the portfolio fluctuates that much, or more, almost with every heart beat. That's like writing a news story that someone made $20 off of penny stocks as part of their $100K next egg. Also note that it's still an unrealized gain. If GameStop went belly-up tomorrow, the Church would lose all $8.7M...and the portfolio wouldn't even notice. By the way, what is GameStop's weight in the Russell 3000 index? Answer: 0.02%.

Ensign increased its Tesla stake by 39% after growing it 3,500% last year. Wow, the Church really believes in Tesla!

Again, what proportion of the portfolio is that? Answer: 0.93%. Let's compare that to Tesla's weight in the S&P 500: 1.28%. How about in the Russell 3000: 1.07%. So the Church's "agressive" purchase of Tesla brings it to a portfolio weight that is...less than in two of the major U.S. stock indicies. Still impressed?

During a pandemic year the Church's portfolio gained 16.5%, and in the first quarter of this year it has already gained 5.5% Wow, Ensign must employ some real financial whizzes. If only I could get in on the action!

Let's compare the annual and quater-by-quarter performance of Ensign to the S&P 500.

It looks to me like the Church has built a diversified portfolio that more-or-less tracks the S&P 500 [4]. The good news for you is that you don't need the whizzes at Ensign after all [5]. You can easily and cheaply invest your money in the S&P 500 or Russell 3000 using one of a number of ETFs or mutal funds.

Notes:
1. Ensign has been reporting its U.S. stock holdings quarterly to the SEC for just over a year. I assume that Ensign also holds international stocks that are not included in these reports.
2. Some people have strong opinions about how the Church manages its money. I consider it none of my business.
3. All of the analysis, and any errors therein, are mine.
4. We don't know what kind of moves Ensign makes during each quarter, so their actual returns may be more or less than it appears.
5. As a general statement, you shouldn't be trying to match the Church's investments anyway. It is a large institution with long-term goals that will make it's risk profile different than yours. In fact, it's entirely possible that the Church's overall asset allocation is too conservative for what you need.

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U.S. Excess Mortality was Not Higher in 2017

Yesterday over at Millenial Star, Geoff B. asserted that, according to a recent study, the U.S. had higher excess deaths in 2017 than in 2020. He then went on to bemoan government efforts to stop the spread of COVID and asserted that all of the worry was just media and political hype, since 2020 was less deadly than a normal year. Why, he asks, did we fall for the propaganda?

The claim that the U.S. had higher excess death in 2017 seemed unbelievable to me, but at first glance that's what the paper seemed to say. Looking closer, however, it appeared that Geoff--or whoever brought it to his attention--misunderstood the point of the study. Comments at MS are moderated and unfortunately it appears that, rather than argue the merits, my comment was rejected for unknown reasons. Luckily I saved a copy, which I have reproduced below in its entirety. Fewer people will see my explanation here, but I still think it's worth posting.

I don’t think the authors are saying what you think they are saying.

What you think they are saying: U.S. excess deaths in 2017 were greater than deaths from COVID in 2020, therefore 2020 was no big deal in comparison to 2017.

What I think they are saying: Using Europe as a mortality reference, since 2000 the U.S. has a trend of increasing excess deaths, to the point that in 2017 the U.S. lost an excess of people (vs Europe) comparable to COVID in 2020. In other words, mortality in the U.S. sucks compared to Europe. The fact that much of that excess mortality occurs in younger people, resulting in higher years of life lost (YLL) compared to the 2020 pandemic simply highlights the tragic nature of the status quo.

I offer three items in support of my view:
1. The method section states: “We estimate the number of US deaths that would not have occurred at age x, year t if the United States had the set of age-specific death rates of the European standard…”
2. A university press release that quotes the authors.
3. This CDC dashboard (scroll to the bottom) where the effect of COVID compared to other years (including 2017) is visually obvious. If you play with the options, you can find that the total U.S. predicted excess deaths (in comparison with itself, not Europe) for 2020 is 570,621 – 696,637.

So to to re-state, what we consider to be a normal number of deaths is actually an excess of deaths when compared to Europe, and the magnitude of that difference is comparable to 2020 U.S. COVID deaths.

Below is a picture from the CDC dashboard I mentioned. It shows U.S. weekly deaths beginning in 2017, with COVID deaths in blue and non-COVID deaths in green. The orange line indicates the threshold for excess deaths. Bear in mind that the highest point of the peak on the right marks the beginning of 2021, so the nunmbers for 2020 don't tell the whole COVID story. Moreover, based on provisional data, there were 3.36 million total deaths in 2020 compared to 2.81 million in 2017, with COVID as the third leading cause of death.

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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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