In a recent study published on the preprint server medRxiv*, researchers investigated whether the time of day that patients with coronavirus 2019 (COVID-19) receive their vaccinations against coronavirus 2 (SARS-CoV-2) from severe acute respiratory syndrome influences the effectiveness of the vaccine. (IT COMES).
Study: BIOLOGICAL RHYTHMS IN THE EFFECTIVENESS OF THE COVID-19 VACCINE. Image credit: BaLL LunLa/Shutterstock
background
Circadian rhythms are oscillations in biological function that occur regularly and allow the alignment of an organism’s physiological clock with the day and night cycle. Rhythms originate from molecular clocks that regulate gene expression and thus organize cell-based functions into daily cycles. Studies have reported that rhythms affect immunological pathways; however, the impact of circadian rhythms on the outcomes of SARS-CoV-2 vaccinations has not been well characterized.
About the study
In the present population-level study, the researchers examined the associations between the timing of SARS-CoV-2 vaccination and VE in terms of innovative infections (ITVs).
The study included 1,515,754 persons aged ≥12 years with ≥1 time-stamped vaccination and no history of SARS-CoV-2 infections before completing two-dose primary vaccinations. The team retrospectively analyzed EMRs (electronic medical records) from the MHS (Maccabi Health Services) database covering the period from December 19, 2020, to April 25, 2022, including two peaks of ‘SARS-CoV-2 infection observed during the domain of SARS-CoV-2 Delta and Omicron Variants of concern (COV).
Individuals with documented SARS-CoV-2 infections before the date of vaccination and those with missing vaccination time stamps were excluded from the analysis. The primary and secondary study outcomes were novel SARS-CoV-2 infections (ITVs), confirmed by antigen testing or PCR (polymerase chain reaction) analysis, and emergency department visits related to SARS-CoV-2 infection, respectively. .
The team mainly compared people who exclusively received their COVID-19 vaccinations in the morning (between 8:00 a.m. and 11:59 p.m.), in the afternoon (12:00 p.m. and 3:59 p.m.) or in the evening ( between 16:00 and 19:00). :59 pm). Multivariate Cox regression model was used for analysis with data adjustments for comorbidities, sex and age, and hazard ratios (HR) and numbers needed to treat (NNT) were calculated ).
results
Almost all (99%) study participants received BNT162b2 COVID-19 messenger ribonucleic acid (mRNA) vaccinations, and the rest were vaccinated with mRNA-1273 vaccines. Most individuals were vaccinated within a 12-hour period between 8 am and 8 pm. Among those vaccinated, 313,844 individuals, 292,278 individuals, and 236,348 individuals received D1 and D2 exclusively in the morning, afternoon, and evening, respectively.
The team excluded 11%, 10% and 12% and 9% of individuals for the first dose (D1), second dose (D2) and third dose (D3) and fourth dose ( D4), respectively, due to the lack of vaccination. time stamps Among MHS members, 81 percent, six percent, six percent, and six percent were Jews, Orthodox Jews, Arabs, and residents of the former Soviet Union, respectively.
Those vaccinated in the morning and in the evening had an equivalent number of SARS-CoV-2 tests. The number of ITV was different for different times of vaccination, with the highest numbers correlated with night vaccinations and the lowest numbers with vaccinations between LM (last hours of the morning) and EA (first hours of the afternoon). Timing of vaccination remained significant after adjusting for patient sex, comorbidities and age (afternoon versus evening HR 0.9).
Consistent results were obtained for primary (D1 and D2) and booster (D3 and D4) vaccines. A sinusoidal association was observed between the timing of vaccination against SARS-CoV-2 and the risks of ITV, in accordance with a circadian rhythm in VE, with durations between nine hours and 15 hours, depending on the vaccination dose.
The maximum estimated values of changes in HR PTS (peak to trough) for BTI were 0.1, 0.1 and 0.3 for combined D1 and D2, D3 and D4, respectively, making NNT values ranging from 19 to 55 at the end of the study period provided that patients with COVID-19 were transferred from vaccination time slots giving the lowest benefit to the most beneficial.
The timing of SARS-CoV-2 vaccination altered the risks of ITV by between nine and 25%, depending on the number of vaccination doses received and the age of the participants. The immunological benefits of receiving vaccinations during the day were pronounced among individuals younger than 30 years and those older than 60 years. In contrast to the BTI results, ED visits associated with SARS-CoV-2 infection were found to be correlated with study participants’ comorbidities and age, but not with time of vaccination
For primary vaccinations (D1 and D2) and initial booster vaccination (D3), older age correlates with peak HR changes in later daytime hours, likely reflecting changes in biological rhythm and immunological experiences by age For older individuals, circadian rhythms resembled those of D4. Lower ITVs among older people could be because older people adhere to precautionary measures and non-pharmacological interventions (NPIs), such as social distancing and mask use against COVID-19, more than young people, leading to less exposure to SARS-CoV-2.
conclusion
In summary, based on the study findings, vaccinations against SARS-CoV-2 between the hours of LM and EA were significantly associated with less BTI than other vaccination times. The timing of SARS-CoV-2 vaccination altered the risk of VTI between 8.6% and 25%, depending on the age of the patients and the number of vaccination doses received. The results highlighted that vaccinating the elderly and children during the hours of LM or EA could confer the maximum vaccine-induced immune benefits.
*Important news
medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered conclusive, guide clinical practice/health-related behavior, or be treated as established information.