COVID-19 And Sleep

What is COVID-19?

The coronavirus disease (COVID-19) is a pulmonary infection caused by a virus known as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This disease is spread through aerosol droplets via the air when an infected person breathes, speaks, sneezes or coughs. Although the majority of the people affected by this disease experience mild to moderate respiratory illness, a select few may become severely ill and subsequently require medical attention. Older people and those with underlying medical conditions like cardiovascular disease, diabetes, chronic respiratory disease or cancer are more susceptible to the disease.

Symptoms of COVID-19

The symptoms of COVID-19 typically present after one to fourteen days of contracting the disease. Some of these symptoms include:

  • High temperature or shivering (chills) – where the person feels hot to the touch on their chest or back
  • New, continuous cough – coughing that lasts for more than an hour or 3 or more coughing episodes in 24 hours
  • Loss or change to a sense of smell or taste
  • Shortness of breath
  • Feeling tired or exhausted
  • An aching body
  • A headache
  • A sore throat
  • A blocked or runny nose
  • Loss of appetite
  • Diarrhoea
  • Feeling sick or being sick

Out of those that exhibit symptoms, around 81% develop mild symptoms such as pneumonia, 14% develop severe symptoms such as dyspnoea (shortness of breath), hypoxia (deprivation of oxygen in the body) and 5% develop critical symptoms such as respiratory failure, shock or multiorgan dysfunction.2 However, at least one-third of the people are asymptomatic.2 

Sleep is crucial for recovery from illness

The symptoms of COVID-19 have transcended beyond solely impacting physical health. Many studies have implicated its effect on daily activities and mental health due to either the infection itself or associated quarantines and lockdowns. Additionally, as COVID-19 has progressed, some of the symptoms have persisted even after the infection, also known as long COVID. In fact, as of 2022, at least 17 million people across the 53 member states of the WHO European Region may have experienced long COVID.3 Furthermore, studies have shown that between 21.7-53% of people suffering from long COVID have sleeping disorders or insomnia.4 

The sleep cycle consists of two phases, rapid eye movement (REM) sleep and non-rapid eye movement (NREM) sleep. The NREM sleep is further subdivided into the phases of light (N1), deeper (N2) and deepest sleep (N3). Humans need to have approximately four to six of these cycles per night, with ninety minutes in each cycle.5

Each of these phases plays an important role; therefore, disruptions in the sleep cycle can vastly impact health.

  • REM Sleep: This phase typically lasts 10 minutes, with the final one lasting up to an hour. REM is usually associated with dreaming and is not considered the ‘restful’ stage of sleep. This is because of the high levels of a hormone called acetylcholine, also known as the ‘wakefulness’ hormone. Furthermore, the brain is highly active during REM sleep, and its metabolic activity increases by up to 20% at this point in the night.6
  • Light Sleep (N1): This phase usually lasts around 5 minutes of the cycle. At this point, the muscles start to relax, and the breathing rate is regular, further transitioning the body into a deep sleep.5
  • Deep Sleep (N2): This phase lasts around 25 minutes but gets longer after each cycle. During this cycle, an individual’s heart rate and body temperature drop, and teeth grinding may also occur. The important function of maintaining sleep and memory retention takes place during this stage.7
  • Deepest Sleep (N3): This stage of sleep lasts for about 20 to 40 minutes and gets shorter as each cycle progresses. During this phase, the body repairs itself: tissue, bone and muscle regeneration occurs, and the immune system is strengthened. Studies have shown that if an individual is awoken during this stage, they may have impaired cognitive performance from 30 minutes up to an hour. Furthermore, it can also lead to sleep inertia, causing symptoms such as mental fogginess, grogginess, disorientation and drowsiness.8 

Collaboratively sleep has multifunctional roles that aid in recovery,9 these include:

  • Cognitive, developmental and memory functions
  • Emotional regulation
  • Energy conservation
  • Biosynthesis of hormones and enzymes
  • Removal of toxic substances and metabolic waste from the brain
  • Modulation of the immune response

Immune response and sleep

Infection -> cell damage -> release of cytokines -> sleep promotion

The key players involved in detecting an infection are:

  1. Specialised Cells: Cells in the brain, such as the neurons and glial cells and cells responsible for immunity, communicate via chemical signals such as hormones, neurotransmitters and modulators: cytokines and chemokines. These cells have specific receptors on their body that are able to detect and receive these signals.10
  2. The Blood-Brain Barrier: The blood-brain barrier is a region where blood from the body is circulated through the brain. The chemical signals produced by both the brain and immune cells can move bidirectionally across the barrier.11 
  3. Activation of Immune Cells: Immune cells can detect foreign matter, such as bacteria and viruses. They can also traffic to all sites of the body, including the nerve endings, the meningeal borders and the cerebrospinal fluid.12 Upon detecting foreign matter, the immune cells themselves can migrate across the blood-brain barrier and send distress signals. 
  4. Primary And Secondary Lymphatic Tissues: Primary (thymus and bone marrow) and secondary lymphatic tissues (spleen and lymph nodes) can subsequently sense signals sent by the brain and immune cells and can further receive signals to make more immune cells during an infection.  
  5. The Endocrine System: This system can directly influence the immune system through hormones and neural activation. They can also indirectly influence the immune system by changing blood flow, blood pressure, lymph flow and the supply of substrates (e.g. glucose, fatty acids and oxygen).14

Sleep promotes the initiation of an immune response. During an infection, when the immune cells detect the foreign cells, they generate a long-lasting immunological memory for this cell. Sleep can cause the activation of a pro-inflammatory response by employing hormones such as growth hormone, prolactin release and cortisol (stress hormone) to fight off infections.15 The hormonal changes in turn support the early stages of generating an immune response in the lymph nodes. Furthermore, cytokines that are produced during the activation of the neuronal and inflammation pathways can promote sleep, such as:16

  • Interleukins: 1ɑ, 2, 6, 8,15,18
  • Epidermal growth factor
  • Acidic fibroblast growth factor
  • Erythropoietin
  • Nerve growth factor
  • Brain-derived neurotrophic factor
  • Glia-derived neurotrophic factor
  • Neurotrophins: 3, 4
  • Interferons: ɑ, ɣ
  • Tumour necrosis factor: β
  • Granulocyte-macrophage colony-stimulating factor

Illness can disturb sleep patterns

Many of the symptoms of COVID-19 overlap with long COVID. Specifically, some of the symptoms like breathing difficulties, headaches, depression, anxiety, fatigue and insomnia can all interfere with sleep. Furthermore, the mass inflammation around the body can lead to physical symptoms of pain, high basal temperature and discomfort. Studies have shown that these symptoms persisted more in people with long COVID, as opposed to those who were never infected.17

Conclusion

As previously mentioned, long COVID can drastically change the lifestyles of those affected by it. However, the keynotes to take away are to not rush your recovery and prioritise your sleep. Consider the effects of having a good pre-bedtime routine:

  • Consistent Sleep Routine: Try waking up and sleeping at consistent times every night.
  • Exercising During The Day: Tire yourself out! Try going for a run or getting some exercise; however, make sure that this is done at least 90 minutes to 3 hours before bedtime.
  • Relax Before Bed: Avoid the use of screens (e.g. mobile phones, laptops and TV) and instead try reading a book, meditating, doing yoga stretches or taking a relaxing bath. Try essential oils.
  • An Ambient Bedroom: Make sure your room is dark, and try candles or a dim night light before bed! Make sure your room is quiet and use curtains, an eye mask or earplugs if needed, or try soothing sounds ~ like a fireplace or raindrops.
  • A Comfortable Bed: Make sure your bed is comfortable with good mattresses and pillows, linen and weighted blankets.
  • Seek Professional Help: If you are suffering from symptoms of long COVID, seek professional help to target the symptoms for a better night’s sleep. Ask a pharmacist or a doctor for help with sleep, and they may provide you with tablets or liquids (sometimes called sleeping aids) or advise you on natural alternatives such as valerian, lavender or melatonin, while others may suggest drugs like Nytol, which are antihistamines. They cannot cure insomnia but may help you sleep better for 1 to 2 weeks until a good sleeping pattern is established, and they should not be taken any longer. 

References

  1. ‘Coronavirus (COVID-19) Symptoms in Adults’. Nhs.Uk, 2 June 2020, https://www.nhs.uk/conditions/coronavirus-covid-19/symptoms/main-symptoms/.
  2. Oran, Daniel P., and Eric J. Topol. ‘The Proportion of SARS-CoV-2 Infections That Are Asymptomatic: A Systematic Review’. Annals of Internal Medicine, vol. 174, no. 5, May 2021, pp. 655–62. DOI.org (Crossref), https://doi.org/10.7326/M20-6976.
  3. At Least 17 Million People in the WHO European Region Experienced Long COVID in the First Two Years of the Pandemic; Millions May Have to Live with It for Years to Come. https://www.who.int/europe/news/item/13-09-2022-at-least-17-million-people-in-the-who-european-region-experienced-long-covid-in-the-first-two-years-of-the-pandemic--millions-may-have-to-live-with-it-for-years-to-come. Accessed 7 Oct. 2022.
  4. Cabrera Martimbianco, Ana Luiza, et al. ‘Frequency, Signs and Symptoms, and Criteria Adopted for Long COVID‐19: A Systematic Review’. International Journal of Clinical Practice, vol. 75, no. 10, Oct. 2021. DOI.org (Crossref), https://doi.org/10.1111/ijcp.14357.
  5. Patel, Aakash K., et al. ‘Physiology, Sleep Stages’. StatPearls, StatPearls Publishing, 2022. PubMed, http://www.ncbi.nlm.nih.gov/books/NBK526132/.
  6. Peever, John, and Patrick M. Fuller. ‘The Biology of REM Sleep’. Current Biology: CB, vol. 27, no. 22, Nov. 2017, pp. R1237–48. PubMed, https://doi.org/10.1016/j.cub.2017.10.026.
  7. Gandhi, Mustafa H., and Prabhu D. Emmady. ‘Physiology, K Complex’. StatPearls, StatPearls Publishing, 2022. PubMed, http://www.ncbi.nlm.nih.gov/books/NBK557469/.
  8. Hilditch, Cassie J., and Andrew W. McHill. ‘Sleep Inertia: Current Insights’. Nature and Science of Sleep, vol. 11, 2019, pp. 155–65. PubMed, https://doi.org/10.2147/NSS.S188911.
  9. Zielinski, Mark R., et al. ‘Functions and Mechanisms of Sleep’. AIMS Neuroscience, vol. 3, no. 1, 2016, pp. 67–104. PubMed Central, https://doi.org/10.3934/Neuroscience.2016.1.67.
  10. Besedovsky, H. O., and A. del Rey. “Immune-Neuro-Endocrine Interactions: Facts and Hypotheses.” Endocrine Reviews, vol. 17, no. 1, Feb. 1996, pp. 64–102. PubMed, https://doi.org/10.1210/edrv-17-1-64.
  11. Capuron, Lucile, and Andrew H. Miller. “Immune System to Brain Signalling: Neuropsychopharmacological Implications.” Pharmacology & Therapeutics, vol. 130, no. 2, May 2011, pp. 226–38. PubMed, https://doi.org/10.1016/j.pharmthera.2011.01.014.
  12. Ron-Harel, Noga, et al. “Brain Homeostasis Is Maintained by ‘Danger’ Signals Stimulating a Supportive Immune Response within the Brain’s Borders.” Brain, Behaviour, and Immunity, vol. 25, no. 5, July 2011, pp. 1036–43. PubMed, https://doi.org/10.1016/j.bbi.2010.12.011.
  13. Nance, Dwight M., and Virginia M. Sanders. “Autonomic Innervation and Regulation of the Immune System (1987-2007).” Brain, Behaviour, and Immunity, vol. 21, no. 6, Aug. 2007, pp. 736–45. PubMed, https://doi.org/10.1016/j.bbi.2007.03.008.
  14. Straub, R. H., et al. “Energy Regulation and Neuroendocrine-Immune Control in Chronic Inflammatory Diseases.” Journal of Internal Medicine, vol. 267, no. 6, June 2010, pp. 543–60. PubMed, https://doi.org/10.1111/j.1365-2796.2010.02218.x.
  15. BrainImmune - Trends In Neuroendocrine Immunology. https://brainimmune.com/. Accessed 12 Oct. 2022.
  16. Krueger, James M. ‘The Role of Cytokines in Sleep Regulation’. Current Pharmaceutical Design, vol. 14, no. 32, 2008, pp. 3408–16. PubMed Central, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2692603/.
  17. Orrù, Graziella, et al. ‘Long-COVID Syndrome? A Study on the Persistence of Neurological, Psychological and Physiological Symptoms’. Healthcare, vol. 9, no. 5, May 2021, p. 575. DOI.org (Crossref), https://doi.org/10.3390/healthcare9050575.

Jade Roberts

Master of Research - (MRes), Biomedical Sciences, Imperial College London
Jade is currently a PhD student at the University of Reading. Her research focuses on how cells can mechanically and electrically interact in response to mechanical movements. Her specialties are cardiovascular biology, electrophysiology, and biomedical engineering.

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