ABSTRACT
Introduction: Circadian 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. Methods: The 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 am10 am), midday (10 am2 pm), late afternoon (2 pm6 pm) or evening (6 pm10 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. Results: Data 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. Conclusion: ML techniques identified demographic and time-ofday- 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.
ABSTRACT
Extrapulmonary symptoms such as cutaneous manifestations are increasingly being reported in coronavirus disease 2019 (COVID-19) infection. The rashes of COVID-19 are usually livedo and purpuric and have been classified into six main patterns. This is the first case reported in Malaysia of ecchymosis associated with COVID-19 occurring on a patient without prior history of coagulopathy. The report of this rare clinical association could have a potential pathophysiological implication and contributes to the current data of the cutaneous manifestations of COVID-19. Further knowledge regarding these cutaneous lesions could help in the diagnosis of COVID-19 related complications and earlier management.