Time of day for COVID-19 vaccine shot may affect immune response, study suggests

Can the time of day you get your COVID-19 vaccine affect how many antibodies you'll make?

A new study suggests that it can.

Researchers found higher antibody levels in health care workers who received their vaccines in the afternoon, and they suggest that response to the vaccine may be affected by circadian rhythms.

"Our observational study provides proof of concept that time of day affects immune response to [COVID-19] vaccination, findings that may be relevant for optimizing the vaccine's efficacy," said co-senior study author Dr. Elizabeth Klerman.

She's a research investigator in the Division of Neurophysiology's Unit at Massachusetts General Hospital.

Klerman emphasized that getting vaccinated, regardless of the time of day, is the most critical step in preventing COVID-19 infection.

Her team evaluated antibody levels among nearly 2,800 health care workers in Britain, whose blood samples were collected at the time of vaccination as part of the British infection prevention program.

The researchers created a model to investigate the effect on antibody levels based on time of day of vaccination, vaccine type -- Pfizer or AstraZeneca -- age, sex and the number of days post-vaccination.

They found that antibody responses were higher in general for everyone who was vaccinated later in the day. Other groups that had higher antibody responses were those who received the Pfizer vaccine, women and younger people.

While symptoms of some diseases and the effect of medications can also vary by time of day, this research contrasts with earlier studies in elderly men who had higher numbers of anti-influenza titers after getting flu shots in the morning.

"The [COVID-19] vaccine and the influenza vaccine have different mechanisms of action from each other, and antibody response may vary greatly depending on whether the immune system recognizes the pathogen from earlier infections, such as influenza, or whether it is confronted by a novel virus," Klerman said in a hospital news release.

A limitation of the study was the lack of data on participants' medical and medication history, their and shift-work patterns, which can also influence vaccine responses.

"We need to replicate our findings and develop a better understanding of the underlying physiology of [COVID-19] and the body's response to vaccination[s] before we can recommend that people who want an extra boost from the vaccine, such as older individuals or those who are immunocompromised, schedule their vaccine for the afternoon," Klerman said.

"This research is the first step in demonstrating the importance of time-of-day response to [COVID-19] vaccine," Klerman said.

Klerman and her colleagues are now analyzing data on vaccine side effects from people who got their shots at Mass General Brigham facilities.

She also hopes to have the opportunity to reanalyze data from randomized, controlled trials of the COVID-19 vaccine, to determine whether the time of day participants received the vaccine affected its efficacy.

"If antibody levels are higher when people receive the vaccine in the afternoon, we may see that side effects are also greater," Klerman suggested.

The findings were published this month in the Journal of Biological Rhythms.

More information

The U.S. Centers for Disease Control and Prevention has more on COVID-19 vaccines.