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The Second COVID-19 Shot Is a Rude Reawakening for Immune Cells
Side effects are just a sign that protection is kicking in as it should.
KATHERINE J. WU FEBRUARY 2, 2021
Editor’s Note: The Atlantic is making vital coverage of the coronavirus available to all readers. Find the collection here.
[Excerpts] At about 2 a.m. on Thursday morning, I woke to find my husband shivering beside me. For hours, he had been tossing in bed, exhausted but unable to sleep, nursing chills, a fever, and an agonizingly sore left arm. His teeth chattered. His forehead was freckled with sweat. And as I lay next to him, cinching blanket after blanket around his arms, I felt an immense sense of relief. All this misery was a sign that the immune cells in his body had been riled up by the second shot of a COVID-19 vaccine, and were well on their way to guarding him from future disease.
Side effects are a natural part of the vaccination process, as my colleague Sarah Zhang has written. Not everyone will experience them. But the two COVID-19 vaccines cleared for emergency use in the United States, made by Pfizer/BioNTech and Moderna, already have reputations for raising the hackles of the immune system: In both companies’ clinical trials, at least a third of the volunteers ended up with symptoms such as headaches and fatigue; fevers like my husband’s were less common.
Dose No. 2 is more likely to pack a punch—in large part because the effects of the second shot build iteratively on the first.
When hit with the second injection, the immune system recognizes the onslaught, and starts to take it even more seriously. The body’s encore act, uncomfortable though it might be, is evidence that the immune system is solidifying its defenses against the virus.
When the immune system detects a virus, it will dispatch cells and molecules to memorize its features so it can be fought off more swiftly in the future. Vaccines impart these same lessons without involving the disease-causing pathogen itself—the immunological equivalent of training wheels or water wings.
The Pfizer and Moderna vaccines accomplish that pedagogy via a genetic molecule called mRNA that’s naturally found in human cells. Once delivered into the upper arm, the mRNA instructs the body’s own cells to produce a coronavirus protein called spike—a molecule that elicits powerful, infection-fighting antibody responses in people battling COVID-19.
To ensure safe passage of mRNA into cells, the vaccine makers swathed the molecules in greasy bubbles called lipid nanoparticles. These strange, fatty spheres don’t resemble anything naturally present in the body, and they trip the sensors of a cavalry of fast-acting immune cells, called innate immune cells, that patrol the body for foreign matter. Once they spot the nanoparticles, these cells dispatch molecular alarms called cytokines that recruit other immune cells to the site of injection. Marshaling these reinforcements is important, but the influx of cells and molecules makes the upper arm swollen and sore. The congregating cells spew out more cytokines still, flooding the rest of the body with signals that can seed system-wide symptoms such as fever and fatigue.
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