Sleep, Immune Function, and Vaccination in Military Personnel: Challenges and Future Directions
Sleep deprivation, characterized by insufficient sleep duration, poor sleep quality, and/or disrupted sleep patterns, has detrimental effects on various bodily systems and increases the risk of diseases. The relationship between sleep and health is bidirectional—illness exacerbates sleep deprivation, and sleep deprivation negatively impacts disease treatment outcomes, leading to prolonged recovery periods. According to the 2015 Department of Defense Health Behavior Survey, military personnel are at twice the risk of sleep deprivation compared to their civilian counterparts. Factors affecting military personnel's sleep are complex and widespread, including intense physical and mental training, irregular schedules, and poor sleeping environments.
Regular sleep is crucial for maintaining a well-functioning immune system and enhancing immunity. Lack of sleep amplifies pro-inflammatory signals, increasing the risk of infections. Conversely, infections activate the immune system, altering cytokine levels and thereby affecting sleep. Many immune-regulating molecules, especially those related to inflammation, such as interleukin-1, tumor necrosis factor-alpha, prostaglandins, and growth factors, are also involved in sleep regulation. Furthermore, components of cell membranes, like peptidoglycans and lipopolysaccharides, can activate the immune system, promote inflammatory responses, and impact sleep.
Research on the relationship between sleep and infection in military personnel is limited. A study conducted on British Army recruits found that those who slept less than six hours had a fourfold increased risk of respiratory infections, such as COVID-19, compared to those who slept 7-9 hours, leading to more training days lost. This study focused solely on COVID-19, indicating the need for further research into the roles of sleep, infection, and overall health in military personnel. Recent studies on the general population have shown a correlation between sleep quality and the severity of COVID-19 symptoms.
Sleep and immunity are among the numerous activities regulated by the central biological clock in the hypothalamus. Disrupted circadian rhythms lead to sleep disorders, such as daytime sleepiness and nighttime insomnia, and affect the immune system in multiple ways: (1) The central biological clock controls the diurnal rhythms of immune mediators; (2) Circadian rhythms influence viral susceptibility, with disrupted rhythms leading to rapid viral replication and spread; (3) Bacterial endotoxin and exotoxin responses and pro-inflammatory cytokine reactions are regulated by circadian rhythms, affecting disease onset and progression; (4) Circadian rhythms impact vaccination, influencing antibody response and seroconversion. Thus, sleep, circadian rhythms, and the immune system are interconnected, mutually influencing and modulating each other.
Circadian Disruption, Sleep Deprivation, and Military Vaccination Challenges
Circadian rhythm disruption and sleep deprivation often occur together. For example, before starting basic training, new U.S. military recruits travel across time zones to reach the training camps. Once training begins, they must quickly adjust to an early sleep schedule, disrupting their original rhythms and shortening sleep duration, impacting sleep quality. Some training activities further exacerbate this, such as the Marine Corps' "Crucible," a 54-hour final test during which recruits sleep only eight hours while completing various high-intensity tasks, including nighttime infiltration and marches. Infectious diseases are more prevalent during U.S. basic training compared to civilian peers, with higher respiratory infection rates. Recruits must complete initial vaccinations within the first few days of arrival at the training camps and receive multiple booster shots throughout the training period. The U.S. military has invested heavily in immunization for infectious disease prevention, as illustrated by historical successes like President George Washington's smallpox inoculation program, influenza vaccination during World War II, and the reintroduction of the adenovirus vaccine in 2011. Despite vaccination, disease outbreaks still occur frequently, as evidenced by adenovirus, influenza, and COVID-19 cases post-vaccination in training camps. The Armed Forces Health Surveillance Branch's 2019-2020 mid-season flu vaccine effectiveness report showed only low-to-moderate protection levels for active duty personnel (adjusted effectiveness [95% CI] = 12% [-10-30] for influenza A, 58% [9-80] for H3N2, and 31% for influenza B). These results highlight the need for strategies to enhance post-vaccination antibody levels and ensure clinical efficacy.
Despite significant investments in vaccination, disease surveillance, and treatment, there is a lack of focus on sleep duration and quality post-vaccination for recruits and all military personnel. Research indicates that sleep deprivation might impact immune responses. For example, studies on the general population have shown that a single night of sleep deprivation immediately after hepatitis A vaccination results in antibody levels at 16 weeks post-vaccination being twice as low compared to non-deprived groups, with lower levels of immune-regulating hormones. Additionally, pre-vaccination sleep duration influences antibody response duration, shortening it by 1-4 months. A recent meta-analysis on sleep duration and vaccine response found that short sleep duration negatively affects antibody production (effect size [95% CI] = 0.79 [0.4-1.18]). These studies suggest that sleep plays a critical role in vaccine-induced immune responses, potentially affecting clinical outcomes, necessitating further research on underlying mechanisms and effects, including for newly developed vaccines like those for COVID-19.
Although sleep deprivation is inevitable in some military tasks and training, the impact on vaccine efficacy during basic training and broader military operations remains unassessed. While vaccines can prevent infectious diseases, no studies have evaluated the effect of sleep deprivation on vaccine response in military personnel or examined the impact of vaccination timing on antibody levels and seroconversion. The awareness of military healthcare providers and commanders regarding the interplay between sleep, vaccination, and immunity is unclear. Lastly, sleep improvement strategies and countermeasures for sleep deprivation need further research and implementation to enhance pre- and post-vaccination sleep quality.
The COVID-19 pandemic and the urgent need for vaccinations have once again highlighted the ongoing threat of infectious diseases to military personnel's health, safety, and readiness. Vaccines remain a crucial tool against these diseases. Therefore, studying the relationship between sleep deprivation and the immune system in military personnel, including antibody production and vaccine efficacy, is of significant importance. The high costs associated with military healthcare, lost man-days, operational impact, and safety incidents due to illness underline the importance of such research. Findings could support future training, vaccination programs, and comprehensive health maintenance for military personnel.
Recommended Future Research Directions:
- Assessing sleep patterns of military personnel before and after vaccination.
- Evaluating immune responses and vaccine efficacy based on pre- and post-vaccination sleep patterns.
- Determining optimal vaccination times influenced by circadian rhythms.
- Testing the effectiveness of sleep improvement strategies to enhance pre- and post-vaccination sleep quality (e.g., maintaining consistent sleep schedules, napping, reducing environmental disturbances).
- Investigating the potential influence of chronotype on sleep, vaccination timing, and immune response.
- Assessing the impact of sleep and circadian rhythm disruptions (e.g., shift work or cross-time zone operations) on post-vaccination immune responses and vaccine efficacy.
- Studying the effects of simultaneous multiple vaccine administrations on immune responses (common in basic training) and the influence of sleep.
- Surveying military commanders' awareness of the relationships between sleep, vaccination, and the immune system.
- Analyzing military healthcare providers' knowledge of the importance of sleep for the immune system and vaccination.
- Evaluating the impact of sleep improvement education and policy implementation before and after vaccination.
Such research could provide valuable insights and evidence to support the comprehensive health maintenance of military personnel, ultimately enhancing their readiness and operational effectiveness.