The global outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has presented numerous challenges to the medical community.

Cano CA, Viereck M, Javaheri S (2024) COVID-19 Associated New Onset Insomnia: A Case Series. JSM Clin Case Rep 12(1): 1235.

The primary manifestations of COVID-19 include respiratory symptoms, but growing evidence suggests impacts on other organ systems, including the central nervous system (CNS) [1]. Sleep disturbances have been increasingly recognized as a sequela of COVID-19 [1]. Insomnia is a sleep disorder characterized by persistent difficulty in falling asleep, staying asleep, or achieving restorative sleep, leading to daytime fatigue, impaired functioning, and reduced quality of life. We present a case series of 4 patients who experienced the onset of insomnia, for the first time, during or shortly after contracting COVD-19.

Ethical Considerations

Permission was obtained from all patients to describe clinical presentations in this report. As such, approval from an Institutional Review Board was not required but this report was written in accordance with ethical principles as mandated by the Declaration of Helsinki.

Patient 1, a 37-year-old woman with no chronic medical conditions, experienced sleep initiation and maintenance insomnia within 2 weeks of recovering from a mild case of COVID-19. She reported episodes of being unable to sleep for 2 to 3 nights per week, and benefited significantly from a combination of hydroxyzine and cognitive behavioral therapy for insomnia (CBT-I). Patient 1 had insomnia for about 6 months before being able to discontinue hydroxyzine and return to her habitual sleep pattern.

Patient 2, a 30-year-old woman with anxiety and migraines, began to experience insomnia during a mild case of COVID-19, initially struggling with sleep maintenance with a reported 3-hour arousal most nights. Within months of her initial infection, she had a second mild case and progressed to having both initiation and maintenance insomnia. Gabapentin improved sleep initiation, but not sleep maintenance. Patient 2 found zolpidem of significant benefit for sleep initiation and maintenance, but switched to mirtazapine due to concern about the risk for possible dependency. Mirtazapine was also beneficial and was used nightly for approximately 30 days: however, she discontinued its use due to concerns about potential weight gain. She realized after discontinuation of mirtazapine that her insomnia had resolved. She also had insomnia for about 6 months before she was able return to her habitual sleep pattern.

Patient 3, a 55-year-old man with ischemic cardiomyopathy with a reduced left ventricular ejection fraction of 15%, atrial flutter, and hypertension, developed sleep initiation and maintenance insomnia shortly after a mild case of COVID-19. Trazodone was of benefit for sleep initiation, but not sleep maintenance. Patient 3 had a history of snoring and excessive daytime sleepiness, but his wife and himself believed that these symptoms became worse after infection. Polysomnography (PSG) revealed mild obstructive sleep apnea (OSA) with apnea hypopnea index (AHI) of 10.4 per hour and an oxygen saturation nadir of 86%. Sleep maintenance improved with positive airway pressure (PAP)-therapy. Patient 3 continued to utilize PAPtherapy and after about 9 months he was able to discontinue trazadone and return to his habitual sleep pattern.

Patient 4, a 76-year-old-old man with hypertension, hyperlipidemia, type 2 diabetes mellitus, and chronic kidney disease, experienced a severe case of COVID-19 that necessitated hospitalization due to confusion and pneumonia. Shortly after infection, he started to experience significant difficulty with initiation and maintenance of sleep and reported routinely only getting 4 hours of fragmented sleep per night. Sleep initiation and maintenance improved significantly with trazodone. He had a history of snoring and excessive daytime sleepiness that, like the previous patient, became worse after infection. PSG revealed severe OSA with an AHI of 59.2 per hour and an oxygen saturation nadir of 84%. Patient 4 opted to treat his OSA with PAP-therapy and he initially had good compliance, but decided to discontinue use after a few months because he did not find it of any benefit. He was last seen about 2 years after infection and reported that he had discontinued trazadone and largely returned to his habitual sleep pattern.

The 4 patients presented did not have a history of insomnia, but developed insomnia for the first time with or shortly after having COVID-19. In the 6-months after COVID-19, the incidence rate of a first-time insomnia diagnosis in survivors, based on review of medical records, was found to overall be 2.53% [1]. COVID-19 severity showed a positive association with first-time insomnia diagnosis incidence rates [1]. Specifically, the rates were 2.23% for un-hospitalized patients, 3.14% for hospitalized patients, and 4.24% for intensive care unit patients [1]. We do not know the natural history of COVID-19-related insomnia, but Whitaker et al.’s study suggested “sleeping difficulty” was one the most persistent non-respiratory symptoms [2]. In our case series, all four patients resumed their habitual sleep pattern without need for pharmacotherapy within a year.

The mechanisms by which COVID-19 may lead to insomnia are likely numerous. Direct invasion of the CNS by SARS-CoV-2 has been observed, with evidence of viral RNA presence in the cerebrospinal fluid (CSF) samples of infected individuals [3]. COVID-19 patients with neurologic symptoms have been found to have anti neural autoantibodies in their CSF [4]. The virus’s neuroinvasive or autoimmune-promoting potential could disrupt normal brain functioning, including sleep regulation. Furthermore, the systemic inflammatory response triggered by infection may contribute to sleep disturbances, as inflammation has been associated with alterations in sleep architecture and in sleep fragmentation [5]. Finally, psychological factors such as anxiety, depression, and stress, which are commonly experienced during the course of infection can significantly impact sleep quality and contribute to the development of insomnia [6].

There are no specific guidelines for the management COVID19-related insomnia, but, in our experience conventional insomnia management techniques are effective. CBT-I may be a valuable intervention and did benefit one of our patients. CBT-I focuses on identifying and modifying negative thoughts and behaviors associated with sleep difficulties, providing patients with effective tools to improve their sleep hygiene and promote healthier sleep patterns. However, as already noted habitual sleep pattern returned to normal within a year in our panel, and so short courses of sleep-promoting medications could also be appropriately considered. However, it is crucial to carefully weigh the potential risks and benefits of medication use, considering individual patient factors and potential drug interactions. Given that insomnia symptoms appeared to resolve under a year in our patient panel if medications are started it is important to reassess whether chronic use is necessary at various time points. Furthermore, identifying and addressing underlying sleep disorders, such as OSA and restless legs syndrome, will likely also be of benefit in managing COVID-19-related insomnia and sleep health in general.

Moving forward, COVID-19 remains a significant medical concern; but, thankfully, the incidence of patients seeking care in our sleep clinic due to new-onset insomnia during or shortly after infection has become less common and may be because recent data has shown that the risk of insomnia as a COVID-related outcome was more common with the Delta variants and less common with the more recent Omicron variants [7]. Immunization against COVID-19 may also play a role in the reduced incidence of newonset insomnia with COVID infection. Nonetheless, it is important to consider and treat insomnia among patients with COVID and/or long COVID, particularly given that insomnia symptoms may persist well beyond resolution of respiratory symptoms. Overall, however, chronic insomnia predating development of COVID continues to have a major health impact on our patient population, but new onset insomnia does not appear to be a component of long COVID in our clinic population.

1. Taquet M, Geddes JR, Husain M, Luciano S, Harrison PJ. 6-month neurological and psychiatric outcomes in 236 379 survivors of COVID-19: a retrospective cohort study using electronic health records. Lancet Psychiatry. 2021; 8: 416-427.

2. Whitaker M, Elliott J, Chadeau-Hyam M, Riley S, Darzi A, Cooke G, et al. Persistent COVID-19 symptoms in a community study of 606,434 people in England. Nat Commun. 2022; 13: 1957.

3. Bougakov D, Podell K, Goldberg E. Multiple Neuroinvasive Pathways in COVID-19. Mol Neurobiol. 2021; 58: 564-575.

4. Song E, Bartley CM, Chow RD, Ngo TT, Jiang R, Zamecnik CR, et al. Divergent and self-reactive immune responses in the CNS of COVID-19 patients with neurological symptoms. Cell Rep Med. 2021; 2: 100288.

5. Irwin MR. Why sleep is important for health: a psychoneuroimmunology perspective. Annu Rev Psychol. 2015; 66: 143-72.

6. Casagrande M, Favieri F, Tambelli R, Forte G. The enemy who sealed the world: effects quarantine due to the COVID-19 on sleep quality, anxiety, and psychological distress in the Italian population. Sleep Med. 2020; 75: 12-20.

7. Taquet M, Sillett R, Zhu L, Mendel J, Camplisson I, Dercon Q, et al. Neurological and psychiatric risk trajectories after SARS-CoV-2 infection: an analysis of 2-year retrospective cohort studies including 1?284?437 patients. Lancet Psychiatry. 2022; 9: 815-827