If the first shot provided the body’s defenses with the scent of a key protein from the SARS-CoV-2 virus, then the immune system was ready to pounce when it saw that spike protein again with shot #2. It was all in the name of building up a lasting and robust blockade in the body, but it did mean some people had quite a hangover after the second dose.

“The immune system goes, ‘I know what this is,’ and attacks it more vigorously,” said Kawsar Talaat, a Johns Hopkins infectious disease physician and vaccine researcher.

Talaat said that it’s possible that, because the immune system is already primed to recognize and target the spike protein, some people could experience something similar after a third dose.

But Slifka offered another hypothesis, one where perhaps the third shot won’t be as bad, or won’t affect as many people. In the United States, second doses were given three to four weeks after the first dose, so the immune system was still in a heightened state from that first shot. Maybe, Slifka said, if people aren’t getting boosters until at least eight months later, their immune systems will have calmed, and the third shot won’t come with quite the kick the second shot did.