Identifying Modifiable Predictors of COVID-19 Vaccine Side Effects: A Machine Learning Approach.

Side effects of COVID-19 or other vaccinations may affect an individual's safety, ability to work or care for self or others, and/or willingness to be vaccinated. Identifying modifiable factors that influence these side effects may increase the number of people vaccinated. In this observational study, data were from individuals who received an mRNA COVID-19 vaccine between December 2020 and April 2021 and responded to at least one post-vaccination symptoms survey that was sent daily for three days after each vaccination. We excluded those with a COVID-19 diagnosis or positive SARS-CoV2 test within one week after their vaccination because of the overlap of symptoms. We used machine learning techniques to analyze the data after the first vaccination. Data from 50,484 individuals (73% female, 18 to 95 years old) were included in the primary analysis. Demographics, history of an epinephrine autoinjector prescription, allergy history category (e.g., food, vaccine, medication, insect sting, seasonal), prior COVID-19 diagnosis or positive test, and vaccine manufacturer were identified as factors associated with allergic and non-allergic side effects; vaccination time 6:00-10:59 was associated with more non-allergic side effects. Randomized controlled trials should be conducted to quantify the relative effect of modifiable factors, such as time of vaccination.

Time-of-Day Variation in SARS-CoV-2 RNA Levels during the Second Wave of COVID-19.

Circadian rhythms influence and coordinate an organism's response to its environment and to invading pathogens. We studied the diurnal variation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in nasal/throat swabs collected in late 2020 to spring 2021 in a population immunologically naïve to SARS-CoV-2 and prior to widespread vaccination. SARS-CoV-2 diagnostic PCR data from 1698 participants showed a significantly higher viral load in samples obtained in the afternoon, in males, and in hospitalised patients when linear mixed modelling was applied. This study illustrates the importance of recording sample collection times when measuring viral replication parameters in clinical and research studies.

The CLASS Study (Circadian Light in Adolescence, Sleep and School): protocol for a prospective, longitudinal cohort to assess sleep, light, circadian timing and academic performance in adolescence.

BACKGROUND: During adolescence, sleep and circadian timing shift later, contributing to restricted sleep duration and irregular sleep-wake patterns. The association of these developmental changes in sleep and circadian timing with cognitive functioning, and consequently academic outcomes, has not been examined prospectively. The role of ambient light exposure in these developmental changes is also not well understood. Here, we describe the protocol for the Circadian Light in Adolescence, Sleep and School (CLASS) Study that will use a longitudinal design to examine the associations of sleep-wake timing, circadian timing and light exposure with academic performance and sleepiness during a critical stage of development. We also describe protocol adaptations to enable remote data collection when required during the COVID-19 pandemic. METHODS: Approximately 220 healthy adolescents aged 12-13 years (school Year 7) will be recruited from the general community in Melbourne, Australia. Participants will be monitored at five 6 monthly time points over 2 years. Sleep and light exposure will be assessed for 2 weeks during the school term, every 6 months, along with self-report questionnaires of daytime sleepiness. Circadian phase will be measured via dim light melatonin onset once each year. Academic performance will be measured via national standardised testing (National Assessment Program-Literacy and Numeracy) and the Wechsler Individual Achievement Test-Australian and New Zealand Standardised Third Edition in school Years 7 and 9. Secondary outcomes, including symptoms of depression, anxiety and sleep disorders, will be measured via questionnaires. DISCUSSION: The CLASS Study will enable a comprehensive longitudinal assessment of changes in sleep-wake timing, circadian phase, light exposure and academic performance across a key developmental stage in adolescence. Findings may inform policies and intervention strategies for secondary school-aged adolescents. ETHICS AND DISSEMINATION: Ethical approval was obtained by the Monash University Human Research Ethics Committee and the Victorian Department of Education. Dissemination plans include scientific publications, scientific conferences, via stakeholders including schools and media. STUDY DATES: Recruitment occurred between October 2019 and September 2021, data collection from 2019 to 2023.

Time of Day of Vaccination Affects SARS-CoV-2 Antibody Responses in an Observational Study of Health Care Workers.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global crisis with unprecedented challenges for public health. Vaccinations against SARS-CoV-2 have slowed the incidence of new infections and reduced disease severity. As the time of day of vaccination has been reported to influence host immune responses to multiple pathogens, we quantified the influence of SARS-CoV-2 vaccination time, vaccine type, participant age, sex, and days post-vaccination on anti-Spike antibody responses in health care workers. The magnitude of the anti-Spike antibody response is associated with the time of day of vaccination, vaccine type, participant age, sex, and days post-vaccination. These results may be relevant for optimising SARS-CoV-2 vaccine efficacy.

In-person vs home schooling during the COVID-19 pandemic: Differences in sleep, circadian timing, and mood in early adolescence.

During the COVID-19 pandemic, schools around the world rapidly transitioned from in-person to remote learning, providing an opportunity to examine the impact of in-person vs remote learning on sleep, circadian timing, and mood. We assessed sleep-wake timing using wrist actigraphy and sleep diaries over 1-2 weeks during in-person learning (n = 28) and remote learning (n = 58, where n = 27 were repeat assessments) in adolescents (age M ± SD = 12.79 ± 0.42 years). Circadian timing was measured under a single condition in each individual using salivary melatonin (Dim Light Melatonin Onset; DLMO). Online surveys assessed mood (PROMIS Pediatric Anxiety and Depressive Symptoms) and sleepiness (Epworth Sleepiness Scale - Child and Adolescent) in each condition. During remote (vs in-person) learning: (i) on school days, students went to sleep 26 minutes later and woke 49 minutes later, resulting in 22 minutes longer sleep duration (all P < .0001); (ii) DLMO time did not differ significantly between conditions, although participants woke at a later circadian phase (43 minutes, P = .03) during remote learning; and (iii) participants reported significantly lower sleepiness (P = .048) and lower anxiety symptoms (P = .006). Depressive symptoms did not differ between conditions. Changes in mood symptoms were not mediated by sleep. Although remote learning continued to have fixed school start times, removing morning commutes likely enabled adolescents to sleep longer, wake later, and to wake at a later circadian phase. These results indicate that remote learning, or later school start times, may extend sleep and improve some subjective symptoms in adolescents.

Resolving delayed sleep-wake phase disorder with a pandemic: two case reports.

Two patients with delayed sleep-wake phase disorder (DSWPD) demonstrated improvement in sleep quality and duration, reduction in symptoms, and elimination of the need for hypnotic or stimulant medications after changing their sleep schedules in response to the coronavirus disease 2019 (COVID-19) pandemic lockdown work schedule changes. These cases highlight the impact of work schedules on patient health and raise questions about approaches to workplace schedule requirements postpandemic. CITATION: Epstein LJ, Cai A, Klerman EB, Czeisler CA. Resolving delayed sleep-wake phase disorder with a pandemic: two case reports. J Clin Sleep Med. 2022;18(1):315-318.