Six times over the course of a year, some select COVID-19 vaccine recipients at the University of Pennsylvania are rolling up their sleeves for a different kind of needle: one that draws blood.
At each session, 10 vials of scarlet fluid are collected, bar-coded, and archived in laboratory freezers. Some will be tested for various kinds of antibodies, the Y-shaped proteins that the immune system makes in response to a vaccine or to a live infection. Others will be tested for antiviral defenders called T-cells, which are marked with fluorescent "tags" and counted at high speed with a laser.
The goal: to determine how well the COVID-19 vaccines work in the real world.
The answer to this complex question has been on the minds of scientists ever since November, when the first large-scale studies suggested the vaccines could prevent up to 95% of illness.
But those promising results came from rigorous clinical trials, in which participants who met specific criteria were assigned at random to receive either the vaccine or a placebo, allowing their outcomes to be compared. All sorts of people were excluded: pregnant women, people who had previously been infected with COVID-19, and patients with certain cancers, HIV, or severe allergies.
The Penn study, led by E. John Wherry, is among many now underway to answer a variety of open questions. Can some vaccinated people become infected but have no symptoms, thereby potentially transmitting the virus without realizing it? How well do the vaccines work in people with various medical conditions? Is a previous COVID-19 infection equal in protection to a first dose of vaccine?
And for all vaccine recipients, how long does the protection last?
None of the uncertainties is reason to hesitate in getting the vaccines, which are safe and remain our best hope of curbing the pandemic. But the answers will be complicated by the emergence of new coronavirus variants, which could reduce the vaccines' effectiveness, and by the fact that the real world is inevitably messier than a clinical trial.
Said Wherry, an immunologist at Penn's Perelman School of Medicine:
"These are all things keeping all of us up at night."