Six weeks after a mild case of COVID-19 early in the pandemic, Erika Thornes started waking up every night between 2 and 3 a.m. Unable to fall back asleep, she would listen to podcasts, read, and scroll through Twitter before finally dozing off by 4 or 5 a.m. That was more than two years ago and Thornes, a mother to three teenagers in San Diego, still struggles to sleep through the night every now and then.
A similar thing happened to her husband during a recent COVID infection. He was suddenly waking up at 3 a.m. every night. His sleep improved when he stopped testing positive, but the symptom was extreme while it lasted. “He was quite shocked,” she says. “He knew I was waking up, but I don’t think he quite understood the severity of ‘awake.’”
Nightmares. Days without sleep. Waking in a panic in the middle of the night. Sleeping for 18 hours a day. As COVID-19 has swept through the global population, so too have reports of sleep disruptions both during an infection and in the weeks and months beyond.
The links between COVID and sleep are still under investigation, but studies show that bacterial and viral infections, in general, interfere with sleep through physical and psychological mechanisms. Recognizing the potential for the virus to upset sleep, experts say, can help people get the care they need.
How sleep and the immune system affect each other
Sleep is intricately entwined with the immune system, a link both well-known and still mysterious. Getting enough rest can help prevent infections, according to evidence and observations going back thousands of years. But infections can also disrupt sleep in complicated ways.
Studies in animals show that viruses and bacteria alter both the amount of time spent sleeping and the kind of sleep, says John Axelsson, director of the Sleep Laboratory at Stockholm University’s Stress Research Institute in Sweden. When researchers inject rabbits or rodents with moderate doses of bacteria or viruses, the animals sleep more. They get more non-rapid eye movement sleep, a deep restful state thought to be important for recovery; and they spend less time in dream-filled REM sleep.
Cytokines, a category of molecules that can stimulate or slow down inflammation, appear to play a major role in these patterns, Axelsson says. When healthy animals are sleep deprived, levels of some pro-inflammatory cytokines in the brain rise, causing the animals to sleep more than usual. When scientists block these cytokines, animals don’t sleep more—even when they are sleep deprived.
It’s harder to do the same kind of research in people, and results are mixed about how sleep changes during illnesses. But studies suggest that, at least to some extent, inflammatory molecules affect sleep in ways comparable to other animals. In studies from the 1990s and early 2000s, researcher Thomas Pollmächer and colleagues injected people with bits of bacterial cell walls, called endotoxins, and found that mild activation of the immune system increased the drive for sleep and enhanced non-REM sleep.
But once the immune system revved up with increased cytokine levels and symptoms of illness, people experienced more disrupted sleep, not typically seen in animals. “The inflammatory system increases the drive for sleeping," Axelsson says. “But at the same time, it then disrupts your sleep if you get a fever.”
To see how respiratory infections affect human sleep, Axelsson and colleagues recruited 100 healthy adults to keep a detailed sleep diary after experiencing the first symptoms of a respiratory infection while wearing a sleep-tracking device on their wrists. Of the 100 volunteers, 28 people got sick. Overall, those people spent longer in bed and slept more after their symptoms began, the researchers reported in 2019.
But this wasn’t a restful sleep. Infected people had difficulty falling asleep, woke up more, and had a more restless sleep especially when they were most symptomatic. As symptoms eased, sleep improved. Anecdotally, that’s the same pattern reported by many people with COVID—a lot of sleep initially followed by insomnia or other disruptions while sickest. The physiological drive to sleep more while getting sick might be adaptive—helping the body fight off the invader, Axelsson says.
Why sleep problems continue after COVID infection
For many people, sleep troubles don’t end on Day 10 or when a person tests negative. To gauge how often sleep troubles persist, researchers surveyed more than 650 long COVID patients who visited the Cleveland Clinic’s reCOVer Clinic between February 2021 and April 2022. Up to six months after an infection, 41 percent reported sleep disturbances; an additional 7 percent reported disturbances that were severe. Black patients, 12 percent of study participants, were three times more likely to report sleep problems compared with other groups—echoing disparities seen throughout the pandemic, says Cinthia Peña Orbea, a sleep specialist and lead author of the study, which was published in June.
Elsewhere, there have been reports of post-COVID narcolepsy, excessive sleeping, and physically enacting dreams with movements like kicking and talking instead of lying still with typical sleep-induced paralysis, says Monika Haack, a psychoneuroimmunologist at Harvard Medical School in Boston, who co-authored a 2019 review of the links between sleep and disease.
Peña Orbea’s study suggests that long COVID falls in line with other chronic illnesses for causing sleep issues. About 60 percent of people with HIV and more than 50 percent of people with hepatitis C experience poor sleep as do people with ME/CFS, also called chronic fatigue syndrome. People with inflammatory bowel disease, rheumatoid arthritis, and other inflammation-related diseases—all immune disorders—often suffer from lack of sleep.
Haack is investigating the details of how sleep disruption interacts with the immune system. In a study soon to be published, she and colleagues found that disturbing sleep in 24 healthy people led to the production of more molecules that prolonged inflammation and notably, a suppression of molecules that normally stop that inflammation. Even after three full nights of recovery sleep, inflammation persists, emphasizing the need to preserve good sleep in the first place.
Together, evidence illustrates that sleeplessness can cause or exacerbate many symptoms associated with both acute COVID and long COVID, including depression, fatigue, and brain fog. Those symptoms in turn can make it hard to sleep. “It's always bi-directional,” Haack says. Insomnia, sleep apnea, and other disruptions, she says, “all can lower sleep quality, depth, continuity, or regularity, and dampen the immune supporting functions that come with normal sleep.”
Developing drugs for COVID-related sleep disorders?
Ultimately, scientists might be able to develop medications that affect levels of cytokines to improve sleep, says James Krueger, an expert on the biochemistry of sleep at Washington State University in Spokane. But it’s a challenging task because the relationship between cytokines and sleep are extraordinarily complex. Some pro-inflammatory cytokines enhance sleep at low concentrations but at higher concentrations, they lead to wakefulness and fragmented sleep. There are also anti-inflammatory cytokines that mostly inhibit sleep at low concentrations.
Hundreds of proteins interact to regulate the immune system and other processes, Krueger says. COVID and other infections tweak those interactions. Targeting those molecules remains a work in progress. "For complex behaviors and brain processes such as sleep, some new drugs have been developed over the past few years,” he says. “Time will tell if they are better than prior drugs.”
How to improve sleep after COVID
Helping people get better rest during and after COVID infections begins with acknowledging the importance of sleep, Haack says. That can include avoiding medications that disturb sleep, such as opioids, and reducing light, noise, and repeated wakeups for people who are hospitalized.
Establishing regular sleep routines with consistent bedtimes and wakeup times are often a part of insomnia care, Axelsson says. It can also help for people to restrict time in bed to increase sleep efficiency and avoid excessive time spent lying awake.
Haack recommends mindfulness apps to reduce stress and anxiety. For her long COVID patients, Peña Orbea has seen cognitive behavioral therapy led to improvements. “With insomnia, the brain is in a hyper-arousal state,” she says. “We try to reset that arousal state of mind.”
Physical activity and fresh air can help a subset of people who may have stopped going out because of their illness, Axelsson says. But for many with long COVID, exercise can cause serious setbacks, underscoring the need for individualized medical care if sleep problems persist post-COVID.
“Sleep disruption can be quite normal during the acute COVID infection, due to sleep-disrupting symptoms such as pain, coughing, stuffy nose,” Haack says. “If sleep disturbances continue to stay beyond the acute symptomatic phase or start to develop as a new symptom, that is the time to seek help.”