Abstract
IntroductionCircadian rhythms have critical roles in human health. We quantified the effect of time-of-day of COVID-19 vaccination and other covariates on self-reported side effects post vaccination.MethodsThe dataset was created from MassGeneralBrigham (MGB) electronic health records and REDCap survey that collected self-reported symptoms for 1-3 days after each immunization. Variables are demographics (age, sex, race, and ethnicity), vaccine manufacturer, clock time of vaccine administration/appointment, any COVID-19 diagnosis/positive test prior to vaccination, any history of allergy, and any note of epinephrine self-injection (e.g., EpiPen) medication. Time of day groupings were morning (6 am–10 am), midday (10 am–2 pm), late afternoon (2 pm–6 pm) or evening (6 pm–10 pm). Side effects were classified as Allergic (Rash; Hives; Swollen lips, tongue, eyes, or face; Wheezing) and Non-Allergic (New Headache, New Fatigue, Arthralgias, Myalgias, Fever) symptoms. The study was approved by the MGB IRB.Machine learning (ML) techniques (e.g., extreme gradient boosting) were applied to the variables to predict the occurrence of side effects. Stratified k-fold cross validation was used to validate the performance of the ML models. Shapley Additive Explanation values were computed to explain the contribution of each of the variables to the prediction of the occurrence of side effects.ResultsData were from 54,844 individuals. On day 1 after the first vaccination, (i) females, people who received the Moderna vaccine, and those with any allergy history were more likely to report Allergic side effects; and (ii) females, people who received the Janssen vaccine, those who had prior COVID-19 diagnosis ,and those who received their vaccine in the morning or midday and were more likely to report Non-Allergic symptoms. Older persons had fewer side effects of any type.ConclusionML techniques identified demographic and time-of-day-of-vaccination effects on side effects reported on the first day after the first dose of a COVID-19 vaccination. We will use these techniques to test for changes on days 2 and 3 after the first dose, and the first 3 days after the second dose and for the influence of recent night or shiftwork. Future work should target underlying physiological reasons.Support (If Any)
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