The influence of SARS-CoV-2 vaccination time on antibody response in healthcare workers

A recent study posted to the medRxiv* preprint server assesses whether the time of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination impacts the antibody responses. In this study, the researchers from the Harvard Medical School and the University of Oxford observed a significant effect of time of vaccination on the vaccine-induced SARS-CoV-2 immunity, which was estimated by measuring the anti-Spike antibody levels.

Study: Time of day of vaccination affects SARS-CoV-2 antibody responses in an observational study of healthcare workers. Image Credit: Iurii Motov/ Shutterstock


Recently research has highlighted the diurnal nature of innate and adaptive immune responses. Examples show that variations in disease symptoms and severity change according to the time of the day.

The circadian response to inflammation is also reported in the case of Influenza A virus infection of circadian-arrhythmic mice. Specifically, the time of day of Influenza vaccination affects the antibody response; higher titers were observed in the morning. Interestingly, the time of sample collection also had a more significant effect on the antibody responses.

Many have observed the role of circadian signaling in regulating the SARS-CoV-2 host immune response and coronavirus disease 2019 (COVID-19; caused by SARS-CoV-2 infection).

The present team has reported a role for the circadian component BMAL1 in regulating the SARS-CoV-2 replication, possibly influencing the induction of host innate and adaptive responses.

These observations strongly support an association between time and the immune response. Therefore, this study looks at whether the time of SARS-CoV-2 vaccination impacts hosts antibody responses.

About the study

Because healthcare workers were identified as a priority group to receive the SARS-CoV-2 vaccine starting in December 2020, the researchers collected peripheral blood samples from them from December 2020 to Febuary 2021. They tested the samples for anti-Spike and anti-nucleocapsid antibody levels.

Of the total 3425 healthcare workers who gave samples, 2190 people contributed one blood sample, 549 contributed two samples and 45 three or more samples. From these, the researchers excluded the participants who had prior SARS-CoV-2 infection (PCR for viral RNA or anti-nucleocapsid antibody), samples with anti-Spike responses <50 AU, and samples obtained after the second vaccination. There were 67 “non-responders”(values beneath the cut-off (<50) in the anti-Spike assay).

To investigate the effects of time of vaccination on anti-Spike antibody levels, the researchers modeled the variation between participants with fixed factors of time-of-day of vaccination (Time 1, 07:00-10:59; Time 2, 11:00-14:59; Time 3, 15:00-21:59), vaccine type (Pfizer, mRNA bnt162b2 or AstraZeneca, Adenoviral AZD1222), age group (16-29, 30-39, 40-49 or 50-74 years), sex, and the number of days post-vaccination.

They observed significant interactions between days post-vaccination and vaccine type and age. However, this was not associated with the vaccine time. Notably, they reported that data analysis using two-time intervals (before or after 1 pm) presented similar results.

Unlike previous reports, the researchers observed no significant effect of the time of day of sample collection. Therefore, the researchers emphasized the importance of recording the time of vaccination in clinical and research studies. This is also important to consider the time of day factors in future study designs to reduce inter-individual variance and the number of participants needed to obtain statistical significance.

Moreover, they noted that while there were significant differences in the anti-Spike levels detected in participants receiving Pfizer mRNA or AstraZeneca Adenoviral vaccines, both vaccines demonstrated comparable efficacies. This highlights the robust nature of the host antibody response despite the vaccine type.


The primary limitations of the study include; the study does not address longitudinal immune responses and the effect of time-of-day of sample collection; because of no medical history data of the healthcare workers, their health profiles may differ from the general population – except that they had no prior infection with SARS-CoV-2 and were seronegative; and because of limited serological sampling following the second vaccination, it precluded the analysis of time-of-day effects following a two-dose schedule.


The researchers in the present retrospective observational study of healthcare workers showed that the time-of-day of SARS-CoV-2 vaccination affects the antibody response. They recommend additional studies investigating the diurnal nature of innate and adaptive immune responses to the SARS-CoV-2 infection.

*Important notice

medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:

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Gemma Wilson

Gemma is a journalism graduate with keen interest in covering business news – specifically startups. She has as a keen eye for technologies and has predicted quite a few successful startups over the last couple of years.

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