Shannon Romano, a molecular biologist, came down with COVID late last March, about a week after she and her colleagues shut down their lab at Mount Sinai Hospital. A debilitating headache came first, followed by a fever that kept rising, and then excruciating body aches. “I couldn’t sleep. I couldn’t move,” she said. “Every one of my joints just hurt inside.”
It was not an experience she wanted to repeat — ever. So when she became eligible for the COVID-19 vaccine recently, she got the shot.
Two days after her injection, she developed symptoms that felt very familiar. “The way my head hurt and the way my body ached was the same headache and body ache I had when I had COVID,” she said. She recovered quickly, but her body’s intense response to the jab caught her by surprise.
A new study may explain why Romano and many others who have had COVID report these unexpectedly intense reactions to the first shot of a vaccine. In a study posted online Monday, researchers found that people who had previously been infected with the virus reported fatigue, headache, chills, fever, and muscle and joint pain after the first shot more frequently than those who had never been infected. COVID survivors also had far higher antibody levels after both the first and second doses of the vaccine.
Based on these results, the researchers say, people who have had COVID-19 may need only one shot.
“I think one vaccination should be sufficient,” said Florian Krammer, a virus expert at the Icahn School of Medicine at Mount Sinai and an author of the study. “This would also spare individuals from unnecessary pain when getting the second dose and it would free up additional vaccine doses.”
While some scientists agree with his logic, others are more cautious. E. John Wherry, director of the University of Pennsylvania’s Institute for Immunology, said that before pushing for a change in policy, he would like to see data showing that those antibodies were able to stop the virus from replicating. “Just because an antibody binds to a part of the virus does not mean it’s going to protect you from being infected,” he said.
It might also be difficult to identify which people have previously been infected, he said. “Documenting that becomes a really potentially messy public health issue,” he said.
Side effects after vaccination are expected. They show that the immune system is mounting a response and will be better prepared to fight off an infection if the body comes into contact with the virus. The Pfizer and Moderna vaccines are particularly good at evoking a strong response. Most participants in the companies’ trials reported pain at the injection site, and more than half reported fatigue and headaches.
The clinical trials of the authorized vaccines from Pfizer and Moderna, which included more than 30,000 participants each, suggest that most people experience the worst side effects after the second jab. And in the Moderna study, people who had previously been infected actually had fewer side effects than those who hadn’t.
But anecdotally, researchers are hearing from a growing number of people like Romano who felt ill after one shot. “They describe these symptoms much more vigorously,” Wherry said.
That matches what Krammer and his colleagues found in their new study, which has not yet been published in a scientific journal. The researchers assessed symptoms after vaccination in 231 people, of whom 83 had previously been infected, and 148 had not. Both groups widely reported experiencing pain at the injection site after the first dose. But those who had been infected before more often reported fatigue, headache and chills.
The team also looked at how the immune system responded to the vaccine in 109 people — 68 of whom had not previously been infected and 41 who had — and found a more robust antibody response in the latter group. The numbers, however, are small, and so the study’s conclusions will need more research, experts said.
It is not necessarily surprising that previously infected individuals might experience more intense reactions. Both shots contain bits of genetic material that spur the body to manufacture spike proteins, the knobby protrusions on the coronavirus’s surface. People who have already been infected with the virus have immune cells that are primed to recognize these proteins. So when the proteins show up after vaccination, some of those immune cells go on the attack, causing people to feel sick.
Dr. Susan Malinowski, an ophthalmologist in Michigan who had COVID-19 in March, certainly felt like her body was under attack after she received the Moderna vaccine. She got the first shot before lunch on New Year’s Eve. By dinner, she was starting to feel ill. She spent the next two days miserable in bed.
“I had fevers. I had chills. I had night sweats. I had pain everywhere in my body,” she said. “I was actually more ill after the vaccine than I was with COVID.”
Questions about more severe vaccine reactions in people who have already had COVID came up at a Jan. 27 meeting of an expert committee that advises the Centers for Disease Control and Prevention.
Dr. Pablo J. Sánchez, a committee member from the Research Institute at Nationwide Children’s Hospital in Columbus, Ohio, noted that he has heard from people who had a response to the vaccine that was worse than their previous experience with COVID-19. He suggested that a question about prior infection be added to the information that the CDC requests from vaccine recipients. “It’s not asked,” Sánchez said. “I do think that is really important.”
Dr. Tom Shimabukuro of the CDC, who presented safety data to the committee, said that the agency was investigating the issue. “There’s limited data on that right now but we are looking at ways to which we can get better information,” he said.
People who have had COVID seem to be “reacting to the first dose as if it was a second dose,” said Akiko Iwasaki, an immunologist at the Yale School of Medicine. So one dose is probably “more than enough,” she said.
A study published recently reported that surviving a natural infection provided 83% protection from getting infected again over the course of five months. “Giving two doses on top of that appears to be maybe overkill,” she added.(
Shane Crotty, an immunologist at the La Jolla Institute for Immunology, pointed out that a more intense vaccine response typically means better protection. If someone had a big response to the first dose, “I would expect that skipping that second dose would be wise and also that the second dose probably is unnecessary,” he said.
But other immunologists suggest everyone stick to two doses. “I’m a big proponent of the right dosing and right schedule, because that’s how the studies were performed,” said Maria Elena Bottazzi, an immunologist at Baylor College of Medicine in Houston.
And getting two shots doesn’t seem to pose any danger to those who have had COVID.
Still, Malinowski, the ophthalmologist, wishes there were fewer questions and more answers. If vaccine side effects really are more intense in people who have already been infected, health officials could give people a heads up, she said.
“It would be nice to know that, ‘Hey, you might not be able to get out of bed for two days,’” Malinowski said. She has decided not to return for a second dose.
Romano of Mount Sinai Hospital is due for her second shot this month and isn’t sure what she will do. “My friends who are immunologists, we’ve all sort of been discussing this among ourselves,” she said. “Chances are I’ll probably get it. But I want to think about it a little bit more before I do.”