Antibody levels are higher when people receive the COVID-19 vaccine in the afternoon as compared to the morning, according to an observational study.
The research, published in the Journal of Biological Rhythms, demonstrates that our internal 24-hour circadian clock regulates many aspects of physiology, including the response to infectious disease and vaccination.
"Our observational study provides proof of concept that time of day affects immune response to SARS-CoV-2 vaccination, findings that may be relevant for optimising the vaccine's efficacy," said study co-senior author Elizabeth Klerman from Massachusetts General Hospital (MGH), US.
The researchers noted that symptoms of some diseases and the action of numerous medications vary by time of day.
For example, people with lung diseases frequently have greater symptom severity and altered respiratory function at certain times of the day, they said.
A study of elderly men who received influenza vaccination showed that they had higher antibody titers when they received the vaccine in the morning compared with the afternoon, according to the researchers.
"Trials have shown that administering some chemotherapy agents at a specific time of day will effectively target cancer cells but limit toxicity to other cells," said Klerman.
The study authors and other researchers have proposed a role for circadian signalling in regulating SARS-CoV-2 immune responses and COVID-19 severity.
The latest study evaluated antibody levels after SARS-CoV-2 vaccination among 2,190 healthcare workers in the UK.
Blood samples were collected from asymptomatic hospital workers at the time of vaccination.
The researchers created a model to investigate the effect on antibody levels based on time of day of vaccination, vaccine type, 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.
The antibody responses were also higher in those who received the Pfizer mRNA vaccine, in women, and in younger people, in addition to the effect of time of day of vaccination, the researchers said.
The study contrasts with earlier studies in elderly men that reported higher anti-influenza titers in the morning.
"The SARS-CoV-2 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 recognises the pathogen from earlier infections, such as influenza, or whether it is confronted by a novel virus," said Klerman.
A limitation of the study was the lack of data on participants' medical and medication history, their sleep and shift-work patterns, which can also influence vaccine responses, the researchers said.
"We need to replicate our findings and develop a better understanding of the underlying physiology of SARS-CoV-2 and the body's response to vaccination before we can recommend that people who want an extra boost from the vaccine schedule their vaccine for the afternoon," said Klerman.
"This research is the first step in demonstrating the importance of time-of-day response to SARS-CoV-2 vaccine," she said, adding that getting vaccinated, regardless of the time of day, is the most critical step in preventing COVID-19 infection.
The study also highlights the importance of recording the time of vaccination or any intervention in clinical and research studies.
"If preliminary data show a difference in efficacy and adverse effects from a drug or vaccine based on time of day, it would behoove drug companies to administer the drug at the optimal time, which would reduce the number of participants needed to get a statistically significant difference between drug and placebo," Klerman added.