Woman sleeping for immune system.

Circadian Rhythm, Sleep, and Immune Response and the Fight against COVID-19

Written by: Mecene Research Team

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Published

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Time to read 9 min

Note From Dr. Pendleton


This article is my attempt at a simplified summary of a scientific paper I found interesting. I’m passionate about sharing scientific knowledge in a way that’s accessible to everyone. However, it's important to remember that many scientific studies, including this one, may not directly apply to you, let alone all people. For example, some studies are conducted on animals or involve small sample sizes, which limits the generalizability of the results. My goal is to present the information responsibly and in layman’s terms, so please keep in mind that the findings should be interpreted with care.


Medical Disclaimer: This article is for informational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay seeking it because of something you have read on this website. The information in this article is based on a scientific review and should not be used as the sole basis for treatment decisions. Always consult with a healthcare professional before starting any new treatment or therapy.

Overview

The scientific study entitled Circadian Rhythm, Sleep, and Immune Response and the Fight against COVID-19 by Mohammed A. Al-Abri, Saif Al-Yaarubi, and Elias A. Said examines the vital connection between sleep, circadian rhythms, and the immune system in the context of the COVID-19 pandemic. The authors investigate how the body's natural 24-hour cycle, or circadian rhythm, regulates the sleep-wake cycle and affects immune responses by influencing various immune cells and inflammatory molecules. The study highlights that sleep deprivation, common in modern society, can weaken immune defenses by altering the levels of key substances like interleukin-6 (IL-6), making individuals more susceptible to infections such as COVID-19. It also explores the impact of sleep disturbances on different groups, including children, adolescents, healthcare workers, and individuals with conditions like obstructive sleep apnea (OSA), emphasizing the need for good sleep hygiene to maintain a healthy immune system during the pandemic.

How the Circadian Rhythm and Quality Sleep Boost Your Immune System Against COVID-19

Sleep is a crucial part of our daily lives that helps us stay healthy by supporting many body functions, including memory, mood, and the immune system. Our bodies operate on a 24-hour internal clock called the circadian rhythm, which helps control when we sleep and wake up. This rhythm is driven by the brain's suprachiasmatic nucleus in the hypothalamus, which sends signals throughout the body to help it adjust to changes in the environment, like the day and night cycle. At sunset, the signal of dimming light reaches the suprachiasmatic nucleus and produces melatonin, a hormone that helps us fall asleep. The review explains that "melatonin…is secreted into the bloodstream usually two to three hours after sunset to reach every organ in the body."


Sleep is tightly linked to the immune system, which defends the body against infections like COVID-19. "The sleep/wake cycle is one of the most prominent manifestations of the circadian rhythm and communicates tightly with the immune system," which means that when we do not get enough sleep, our body's defenses are weakened. Sleep deprivation, which is very common today, can disrupt immune function, making people more vulnerable to infections and other health issues. The study aims to explore how sleep helps keep the immune system strong, especially during the COVID-19 pandemic. It discusses substances that regulate sleep, like interleukins and interferons, which are molecules involved in the immune response. Also, it looks at how sleep affects different groups of people, including children, healthcare workers, and those with sleep disorders like obstructive sleep apnea (OSA).

Clocks depicting circadian rhythm.

Methodology

The review collects and analyzes findings from many scientific studies to understand the connection between sleep, circadian rhythms, and the immune system. It examines the effects of sleep-regulatory substances, like cytokines (proteins important for cell signaling in the immune system) such as interleukin-1β, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interferon-gamma. These studies help show how these substances change with sleep and how sleep deprivation affects their levels.


Furthermore, this study also looks at how these factors are related to COVID-19 infections. For example, some studies measured cytokine levels and immune cell counts in patients to see how sleep patterns affect their immune responses. Others focused on specific populations, such as children or healthcare workers, to assess how sleep disturbances impact their health during the pandemic.

Main Findings

Circadian Rhythms and Immunity

The circadian rhythm plays a critical role in regulating the immune system. Different types of immune cells, like leukocytes (white blood cells), show daily patterns in their activity. "Leukocytes, such as naive CD4 T cells, monocytes, and neutrophils have nighttime maximum rhythms," meaning their levels peak at night. This timing is controlled by hormones like cortisol, which helps move these cells to the bone marrow. In contrast, "cytotoxic NK cells have daytime maximum rhythms," with their levels peaking during the day, regulated by epinephrine, which helps release these cells into the bloodstream.


The review states, "Pro-inflammatory cytokines such as interleukin (IL)-1β, tumor necrosis factor alpha (TNF-α), interferon gamma, and IL-6 are generally thought to be somnogenic with increased levels during the rest phase," indicating that these molecules promote sleep and reach their highest levels when the body is at rest. In contrast, "anti-inflammatory cytokines, e.g., IL-10 and IL-4, have a negative effect on sleep and are high after waking."

Sleep Deprivation and Immune Response

When people do not get enough sleep, their immune systems become less effective. The research paper highlights that "short sleep duration might depress cellular and humoral immunity," meaning both the immediate and longer-term defenses of the body are weakened. For example, reduced sleep can lower the levels of CD4 T-cells, which are essential for fighting viruses. It can also increase inflammatory substances like IL-6, which can worsen infections.


"Sleep deprivation is associated with an increased level of inflammatory cytokines including IL-6 and a decrease in CD4 T lymphocyte levels," which means that lack of sleep can make it easier for viruses like SARS-CoV-2, which causes COVID-19, to infect the body. This might also lead to more severe symptoms. Studies show that people who do not get enough sleep for several days have lower levels of immune cells and "decreased phagocytosis and NADPH oxidase activity in neutrophils," reducing their ability to fight infections.

Woman sick due to lack of sleep.

COVID-19 and Sleep Interactions

The review shows that poor sleep or sleep deprivation can lead to higher levels of cytokines like IL-6, which are already elevated in people with COVID-19. This can increase the severity of symptoms and the need for intensive care. "Interestingly, a study found that poor sleep quality in hospitalized COVID-19 patients with lymphopenia was associated with a lower absolute lymphocyte count, reduced recovery rate, and an increased requirement for intensive care unit (ICU) care."


This suggests that sleep disturbances could make COVID-19 worse. Treatments that target cytokines, such as IL-6 inhibitors like tocilizumab, have been found to help reduce severe symptoms related to sleep disturbances. The review also discusses how "IL-6 might affect the brain and sleep by an indirect mechanism," as high levels of IL-6 can alter the balance of different types of T cells, which could impact sleep.

Population-Specific Impacts

Children and Adolescents

The COVID-19 pandemic has significantly disrupted sleep patterns in children and teenagers, with many experiencing difficulty falling or staying asleep. "For children aged 4–12 years the main issue was initiating and/or maintaining sleep, and for the 0–3 years group increased nocturnal awakenings." These sleep problems can affect their immune function and general health. Sleep disturbances might have long-term consequences, although "it is still unknown if the adverse changes to sleep patterns and bedtime routines seen during the lockdown will have any long-term consequences for children's sleep and daytime functioning."

Healthcare Workers

Healthcare workers, especially front-line workers, have been under immense stress during the pandemic. Many have experienced disrupted sleep due to long shifts and night duties. "Individuals working night shifts were 1.81 times more likely to sleep less than six hours per day than those who were not working night shifts." This lack of sleep can weaken their immune systems, increase their risk of infection, and contribute to mental health issues like anxiety and depression.

People with Obstructive Sleep Apnea (OSA)

OSA, a condition where a person's breathing repeatedly stops and starts during sleep, is common, affecting about "2–4% of the world population." People with OSA are at greater risk for severe COVID-19 outcomes, such as ICU admission and mechanical ventilation, because "OSAS may cause ventilatory compromise, which would impair ventilation in patients with COVID-19 disease." This is due to reduced oxygen levels during sleep, which can further worsen the condition of COVID-19 patients.

Implications

The findings highlight the importance of maintaining healthy sleep habits, especially during the COVID-19 pandemic. Good sleep helps the body's immune system function properly. It may reduce the risk of severe illness by lowering inflammatory cytokine levels like IL-6 and maintaining the levels of vital immune cells like CD4 T-cells. The review suggests that improving sleep quality through good sleep hygiene practices and addressing sleep disorders like OSA could help people recover better from COVID-19.


For children and adolescents, maintaining consistent sleep schedules and avoiding excessive screen time is essential to protecting their immune health. Healthcare workers could benefit from support systems to help manage sleep disruptions and reduce burnout. The review also suggests that understanding the role of sleep-related substances like melatonin and optimizing medication schedules according to circadian rhythms might improve patient outcomes.

People wearing face masks.

The Vital Role of Sleep in Strengthening Immunity Against COVID-19

Sleep and the immune system are deeply connected, and getting enough quality sleep is crucial for maintaining a strong immune defense against illnesses like COVID-19. The review shows that sleep deprivation and disturbances can increase the risk of severe disease by raising inflammatory markers like IL-6 and reducing immune cell counts.


Ensuring proper sleep hygiene, understanding how substances like melatonin affect the immune system, and addressing sleep disorders like OSA could help improve health outcomes for those affected by COVID-19. More research is needed to explore how these findings can be applied to different groups, such as children, healthcare workers, and those with specific sleep disorders, to help reduce the impact of the virus and improve overall well-being.

Meet the Author

Dr. James Pendleton

Dr. James Pendleton is a primary care physician specializing in a naturopathic approach to family medicine. He has nurtured a family practice in Seattle, directed a VIP medical center in Abu Dhabi, published several books and scientific articles, and designed innovative nutritional supplements for manufacturers worldwide.

REFERENCES

  1. Al-Abri, M. A., Al-Yaarubi, S., & Said, E. A. (2023). Circadian Rhythm, Sleep, and Immune Response and the Fight against COVID-19. Oman medical journal, 38(2), e477. https://doi.org/10.5001/omj.2023.38
  2. Garbarino, S., Lanteri, P., Bragazzi, N. L., Magnavita, N., & Scoditti, E. (2021). Role of sleep deprivation in immune-related disease risk and outcomes. Communications biology, 4(1), 1304. https://doi.org/10.1038/s42003-021-02825-4
  3. Reddy, S., Reddy, V., & Sharma, S. (2023). Physiology, Circadian Rhythm. In StatPearls. StatPearls Publishing. Retrieved from https://pubmed.ncbi.nlm.nih.gov/30137792/
  4. Said, E. A., Al-Abri, M. A., Al-Saidi, I., Al-Balushi, M. S., Al-Busaidi, J. Z., Al-Reesi, I., Koh, C. Y., Idris, M. A., Al-Jabri, A. A., & Habbal, O. (2019). Sleep deprivation alters neutrophil functions and levels of Th1-related chemokines and CD4+ T cells in the blood. Sleep & breathing = Schlaf & Atmung, 23(4), 1331–1339. https://doi.org/10.1007/s11325-019-01851-1
  5. Spicuzza, L., Caruso, D., & Di Maria, G. (2015). Obstructive sleep apnoea syndrome and its management. Therapeutic advances in chronic disease, 6(5), 273–285. https://doi.org/10.1177/2040622315590318
  6. Wang, M., Wei, J., Yang, X., Ni, P., Wang, Y., Zhao, L., Deng, W., Guo, W., Wang, Q., Li, T., & Ma, X. (2019). The level of IL-6 was associated with sleep disturbances in patients with major depressive disorder. Neuropsychiatric disease and treatment, 15, 1695–1700. https://doi.org/10.2147/NDT.S202329