番茄社区

With so much chatter about hefty side effects -- headache, chills, fatigue, body aches -- after the second dose of the Moderna and Pfizer COVID-19 vaccines, the sizeable proportion of people who don't get sidelined by the shots have been wondering if they're still fully protected against the disease.

The short answer from immunologists and infectious disease specialists is, "yes, absolutely."

In phase III trials, the most common side effect after the was fatigue (reported by 60% of those ages 16 to 55), and about 80% of had some type of effect, including fever, fatigue, or muscle pain after dose two -- leaving a substantial number of people without any side effects at all.

Yet the approximate 95% efficacy for both vaccines applied to all participants, regardless of their reaction or lack thereof, said Paul Offit, MD, of Children's Hospital of Philadelphia.

"By definition, there have to be many people who don't have any side effects, and they will still be protected," Offit told 番茄社区.

Offit also pointed out that for both vaccines, "about 25% of those who had placebo had fatigue, so the [vaccine] figure is probably falsely high."

Several immunologists and infectious disease experts interviewed by 番茄社区 said there are no data that a reaction correlates with protection.

"People who don't have a sore arm shouldn't assume they're not protected, and those who do have a sore arm shouldn't assume they're more protected than others," said Robert Schooley, MD, of the University of California San Diego.

"Each of us has a different set of HLA and other immunogenetic mediators that respond to different antigens to different degrees," Schooley noted. "One person may have a vigorous response to a hepatitis B vaccine, while another may not. One person may react strongly to certain adjuvants while others may not."

He added that while there's "more and more science in vaccinology than in the past," clinicians are not yet at the point "where we can do whole-genome sequencing on someone and say, 'you're likely to respond better than someone else.'"

Stanley Weiss, MD, of Rutgers New Jersey Medical School, said it's known from past experience with other vaccines that "people who had no apparent significant reaction still develop very good protection against those agents. We expect that to be the same case here."

However, all of those contacted by 番茄社区 were cautious about protection among immunocompromised and immunosuppressed patients.

"People who are on biologic modifiers like rituximab may not make as vigorous of a neutralizing antibody response even with both vaccine doses," Schooley noted. "That won't correlate with how sore or tired they were."

Those patients need to talk with their doctors about continuing to take precautions even after vaccination, Schooley said. He noted that he measured antibody titers for one of his immunocompromised patients after her vaccine, finding a "minimal" response.

"I told her I'm glad she was vaccinated because she likely has some T-cell response and T cells are very important in being able to clear the virus," Schooley said.

He warned that this doesn't mean that the immunocompromised shouldn't be vaccinated: "It's just a caution that protection levels may not be as high as people who are immunocompetent. But they are very likely to be better protected."

This population needs further study as to whether alternative strategies should be preferred, such as using one vaccine instead of another, using a different dosing interval, or using one brand for the first shot and boosting with a different brand for the second.

He also cautioned that immunocompetent people shouldn't be measuring their antibody levels after vaccination. First, "the presence of antibodies doesn't tell you for certain that someone isn't able to be infected," he said.

Also, not all commercial antibody tests measure those targeting the SARS-CoV-2 spike protein, which is the principal antigen generated by the mRNA and adenovirus-vector vaccines. Clinicians who do move ahead with titering should be sure to choose an assay that looks for antibodies to the spike protein.

Weiss said he's generally satisfied with the efficacy of the vaccines, but a better understanding of the differences in response among different people could help open doors for future vaccine development.

"While 95% efficacy is very high, it's an interesting scientific question as to why that other 5% did not get adequate protection. We just don't have data yet to answer that question," he said.

"I think further investigation of the 5% who were not protected would be worthwhile," Weiss added. "Now with millions of people vaccinated, the sample size could be adequate to explore that type of issue."

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