With the COVID-19 vaccines finally getting into people’s arms, you might’ve heard that your second dose might feel a little rougher than the first. And it’s true. Participants in clinical trials, plus the recently vaccinated public, saw more frequent and more intense side effects on their second jab than their first. This is actually a sign that the vaccines are working properly. So while you should prepare to feel crummy for a couple days, it’s a good thing overall! And it might hint at the possibility of more good news: that people who’ve recovered from COVID-19 could only need one shot.
The key thing to understand is that these reactions to vaccines, things like fever, chills, and other side-effects, aren’t really from the vaccine itself. They’re natural byproducts of your immune system learning to fight the germ the vaccine is teaching it to spot. And that response is stronger after the second shot because the first shot did what it was supposed to do! To understand what I mean, let’s have a quick refresher on how vaccines work. In general, vaccines teach your immune system to spot a pathogen by giving it some harmless version or just part of it to study. That way, if ever encounters a real deal, it’ll know how to fight it. We call this adaptive immunity — but it doesn’t happen immediately. It takes weeks to fully develop the strong, targeted response that vaccines are aiming for. So the first time a vaccine introduces your immune system to a new pathogen, any discomfort you feel is something else: your innate immunity kicking in. This is a generalized first line of defense that attacks anything the body perceives as a threat. And it can definitely have some uncomfortable side effects.
For instance, within a few hours, you can have local reactions, which are things like pain and redness at the injection site or tenderness in the armpit of the arm that received the injection. You can also have systemic reactions that point to a more widespread activation of your immune system. These are symptoms like fatigue, headache, and all-over muscle pain. But often, these side-effects are minor, or maybe not noticeable at all. What matters is what’s happening in the background. While your innate immunity is doing its thing, the immune cells that do the heavy lifting in adaptive immunity are studying the foreign material and building up targeted weapons like antibodies. That way, by the time you get your second dose of the vaccine, your adaptive immunity has the tools it needs to fight the invader. And it does. That, too, can set off local and systemic reactions.
So following your second shot, you get both innate and adaptive immunity acting at once! This is why the side effects are often more severe. This strong, dual immune reaction also ensures your body takes the threat seriously and ramps up its defenses against it even more. So as much as we dislike the potential side effects, the result is lasting protection from the virus. Now, some people get the short end of the stick here. Thanks to their unique experiences and genetic makeup, they really feel it when their immune system gets riled up, while others don’t. And we don’t totally know why. But, if you’re going to feel crummy, the odds are higher it’ll happen in dose number two. And that’s not news—that’s exactly what was seen in the clinical trials for these vaccines.
For example, across all age groups in the Moderna trial, more participants reported some kind of local or systemic reaction on their second dose of the vaccine. And something similar was seen with the BioNTech vaccine, now being distributed by Pfizer. While pain at the injection site was more common after the first dose, the researchers noted more redness and swelling after the second dose, as well as more body-wide reactions like fatigue, fever, and muscle pain. Thankfully, in trials, these effects almost always went away after two or three days. There’s also nothing really special about the side effects occurring now. You’re hearing about them because lots of people are getting vaccinated all at once, and this is a really big deal, and everyone is talking about it.
But these side effects are on par with what’s seen following other multi-dose vaccines given to adults. Take Shingrix, for example, a shingles vaccine you might get if you’re over 50 years old. Most people get a sore arm, while some feel fatigued, have headaches, or muscle pain that lasts a couple of days. That said, some people who’ve already had COVID-19 are reporting something different: they seem to be having those stronger, “second-dose” side effects after dose one. That may be because the disease itself can act kind of like a first vaccine dose, in that it teaches the immune system to spot the virus. So, the first dose of the vaccine may be having similar effects to everyone else’s booster.
What’s nifty about that is that it could mean they only need one dose. To be clear, the vast majority of the clinical trials for these vaccines have only used a two-dose vaccination strategy. So no one has tested this one-vaccine hypothesis! But two recent preprint articles concluded that we might be able to reallocate the limited doses of the mRNA vaccines being distributed by Pfizer and Moderna without compromising safety. One found that people who had recovered from COVID-19 developed at least ten times as many antibodies after one dose of an mRNA vaccine as previously healthy people who got two. And the other found that healthcare workers who had previously had COVID-19 had antibody levels on par with folks who got two doses of the mRNA vaccines but had never been infected. That might mean that previously infected individuals might only need one shot to protect them long-term! And if that’s the case, we may be able to give that second vaccine dose to someone else, and hopefully, get people vaccinated even faster.
Now, each of these studies only had a few hundred participants, and neither has been peer-reviewed, so we can’t start making sweeping statements yet. And there are no changes in policy or anything. So, in the meantime, keep doing what your medical professionals tell you to do! Still, if you have had COVID-19, be warned your first vaccine shot could be the rough one. And for everyone else, it might be helpful to set your expectations ahead of time. Yes, there’s a good chance you’ll feel bad after your second dose in particular, and need to take a day or two to rest and recuperate. But it’ll be worth it, because these expected temporary side effects are way less intense and debilitating than getting a bad case of COVID-19, and we all just want to get through this pandemic so we can relax a little bit.