Insomnia and poor sleep quality are common symptoms associated with SARS-CoV-2 infection. The prevalence of sleep disturbances in people with acute COVID-19 infection is substantial, with some studies reporting rates as high as 75% in hospitalized patients. This difficulty in sleeping, sometimes referred to as “COVID insomnia,” is not simply a result of discomfort or stress. Instead, it involves a complex interplay of direct viral activity and the body’s intense biological response to the pathogen.
How Inflammatory Cytokines Disrupt Sleep Cycles
The primary driver of sleep disruption during an acute infection is the body’s systemic inflammatory response. When the immune system detects the virus, it releases signaling molecules called pro-inflammatory cytokines, such as Interleukin-6 (IL-6) and Tumor Necrosis Factor-alpha (TNF-alpha). These molecules are part of a coordinated defense mechanism intended to promote “sickness behavior,” which includes symptoms like fever, lethargy, and a strong urge to rest.
These signaling molecules can cross the blood-brain barrier or signal receptors on its surface. Once in the brain, cytokines directly interfere with the hypothalamus, a region that regulates the sleep-wake cycle and circadian rhythm. Elevated levels of these inflammatory agents effectively hijack the brain’s sleep machinery, often resulting in a feeling of being exhausted but unable to achieve restorative sleep.
High cytokine concentrations alter normal sleep architecture, specifically reducing the time spent in deep, slow-wave sleep. This fragmented, non-restorative pattern explains the persistent fatigue and daytime sleepiness experienced by many infected individuals. The severity of the sleep problems often correlates with the overall inflammatory load, indicating a clear chemical link between the intensity of the immune response and the quality of sleep.
Direct Viral Effects on the Central Nervous System
Beyond circulating inflammatory chemicals, the SARS-CoV-2 virus may directly affect the brain structures that govern sleep. The virus exhibits neurotropism, meaning it has an affinity for nervous system tissue, and is theorized to enter the central nervous system (CNS) through pathways like the olfactory bulb or the vagus nerve. It uses the Angiotensin-converting enzyme 2 (ACE-2) receptor for entry, which is present on certain cells within the brain.
The presence of the virus or the localized immune reaction it triggers leads to neuroinflammation within the brain. This inflammation can damage or disrupt neurons in areas that regulate specific sleep stages. Key areas like the brainstem and the locus coeruleus, which are involved in the regulation of REM (Rapid Eye Movement) and non-REM sleep, are particularly susceptible to this localized disruption.
Damage to these neuronal populations can cause long-term alterations in sleep patterns, contributing to chronic issues like persistent insomnia or even narcolepsy-like syndromes seen in some recovering patients. This structural or localized functional impact is distinct from the general chemical signaling of systemic inflammation.
Respiratory Symptoms and Sleep Fragmentation
Physical symptoms related to the respiratory system are a mechanical cause of poor sleep during COVID-19 infection. Persistent coughing, a hallmark of the disease, physically jolts the patient awake, leading to frequent and disruptive arousals. Severe nasal congestion also forces a shift to mouth breathing, which degrades sleep quality and can exacerbate dryness and discomfort.
A more serious physiological mechanism is intermittent hypoxia, the repeated drops in blood oxygen levels that occur with compromised lung function. Hypoxia triggers the brain’s arousal system as a survival mechanism. This immediate response prevents the body from entering the deeper, more vulnerable stages of sleep.
The brain interprets a drop in oxygen as a physical threat, forcing a momentary wake-up to reset breathing, which fragments the sleep cycle. Even if the person does not fully wake up, these micro-arousals prevent the sustained deep sleep necessary for physical and mental restoration.
Hormonal Dysregulation of the Sleep-Wake Cycle
The stress of an acute COVID-19 infection, coupled with systemic inflammation, results in dysregulation of the hormones that maintain the 24-hour sleep-wake cycle. The body’s stress response system, known as the Hypothalamic-Pituitary-Adrenal (HPA) axis, becomes overactive. This heightened activity leads to the excessive release of cortisol, the primary stress hormone.
Cortisol levels naturally peak in the morning and dip at night to allow for sleep onset. During an infection, HPA axis dysfunction elevates nighttime cortisol, which directly interferes with the natural dip required for falling and staying asleep. This hormonal imbalance contributes to the feeling of being “wired but tired,” where the body is exhausted but physiologically alert.
Conversely, the infection and resulting inflammation can suppress the production or signaling of melatonin, the hormone that promotes sleep. Melatonin is essential for initiating sleep and regulating circadian timing. The inflammatory environment can inhibit the pineal gland’s ability to produce sufficient melatonin, or it can interfere with how the brain responds to the hormone, thus throwing the body’s internal clock out of sync.