New York: Why the Second COVID Shot Makes You Miserable

When the actress Sarah Wynter got her first dose of the Pfizer COVID-19 vaccine, she didn’t experience any side effects apart from a little soreness in her arm. Dose two was a different story. About 12 hours after she received it, as she was about to go to bed, “it hit me like a freight train,” she says. “I just started feeling very achy, very tired and heavy.”

She woke up the next morning experiencing what felt like the worst hangover of her life. After some Tylenol and coffee, she felt almost better by late morning and was well enough to host a small birthday party for her 10-year-old twins. Then, at bedtime, it was round two, this time including violent chills. A night’s rest helped, but the following day she still felt under the weather.

Wynter’s experiences may not have been exactly typical, but they weren’t unusual, either: The second dose of Moderna and Pfizer vaccines really do pack a wallop. A study by the Centers for Disease Control and Prevention found that while 30 percent of recipients experienced fatigue and a quarter suffered headaches after the first dose, those figures climbed to 54 percent and 46 percent, respectively, after the second dose. The number experiencing chills or fever climbed from 9 percent to 30 percent.

These unpleasant effects are a result of the way the immune system works. When a pathogen like COVID attacks, it destroys cells and triggers a first-wave response, so-called innate immunity, which results in inflammation and activates a horde of white blood cells. It also triggers a second system, so-called acquired immunity. A small number of white blood cells identify unfamiliar proteins associated with the threat, and over the course of the next ten days or so, these cells multiply so they’ll be ready if it ever returns.

A vaccine tries to forewarn the acquired immune system by presenting it with pieces of the pathogen that it can later recognize. But if it does that outside of the context of an innate immune response, the acquired immune system won’t be triggered to react. To fix that problem, vaccines contain substances called adjuvants that biochemically sound the innate-immunity alarm. When you get your first vaccination jab, it’s the adjuvants that tell your body it’s under attack. When you get your second jab, both adjuvants and the pieces of pathogen sound the alarm. “The immune system is already primed and ready to have a bigger response,” says Rachel Roper, a professor of microbiology at East Carolina University.

It takes time for acquired immunity to swing into action, which is why Wynter didn’t start to feel sick until the evening of her shot. After about 24 to 36 hours, her body gradually absorbed the adjuvants and the viral proteins, and the immune system responded by going back to its resting state.

People over 55 are less likely to report being steamrolled by either the first or the second dose because their immune systems have faded with time and are less able to mount a vigorous defense. “The adaptive response decreases as you age,” says Matthew Woodruff, an immunologist at Pace University. “That’s why it’s always more difficult to get a good vaccine response in aging populations.” Seasonal flu shots, which provoke a fairly weak innate immune response and so generally don’t kick anyone’s ass, can trigger such a weak response in older patients that they are sometimes made in special elderly-friendly formulations, which include extra adjuvants. If a young person were to take that version, it would more likely flatten them.

The fact that Pfizer and Moderna vaccines hit some recipients so hard is also due in part to the fact that they were created in record time, in response to a disease that was poorly understood and spreading quickly. “When the scientists originally designed the vaccine trial, they wanted maximum efficacy,” Roper explains. With the focus on saving lives, side effects were a secondary concern. “A much lower dose for the booster may be just as effective with fewer side effects,” she says, “but we don’t have data to prove that.”

(In the race to get their vaccines to market, Moderna and Pfizer were lucky to avoid the rare but more dangerous side effects that have struck some recipients of the AstraZeneca and Johnson & Johnson vaccines. On Tuesday, the CDC and FDA recommended that use of the latter be suspendedpending further investigation after six women suffered a severe type of blood clot and one died.)

For her part, Wynter worries that telling others about her symptoms might discourage others from getting their second shot because “they’re scared of feeling crappy for a couple of days.”

Woodruff sees it as a matter of maintaining public trust. “We in the scientific community and the medical community can’t shy away from talking about this stuff,” he says. “The truth is bigger than any individual vaccine. We have to be open and honest and realistic and talk about the shortcomings and provide a larger context. I think that’s our job.”

The good news is that so far, missing second doses doesn’t seem to be a widespread problem. A March study found that of 12.5 million Americans who had received a first dose, only 3 percent had failed to get the second dose within a permissible time frame. No evidence has emerged since that this number has increased, even as awareness of second-shot side effects has presumably become more widespread. While reluctance to get the vaccine at all is a major concern — and may only ramp up after the Johnson & Johnson snafu — it seems that those who do want to be inoculated are very likely to follow through all the way.

This article was originally published in New York magazine on April 16, 2021.

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