Skip to main content

Advertisement

Springer Nature Link
Log in

Sleep and Long COVID—A Review and Exploration of Sleep Disturbances in Post Acute Sequelae of SARS-COV-2 (PASC) and Therapeutic Possibilities

  • REVIEW
  • Published:
Current Sleep Medicine Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Post Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-COV-2), also known as PASC, and frequently referred to as “long-COVID,” is estimated to afflict over 65 million people worldwide. Sleep disturbances and fatigue are some of the most frequently cited PASC symptoms, and most debilitating. The following text will explore known associations and overlaps between PASC and conditions associated with sleep disturbances, including restless legs syndrome, chronic fatigue syndrome/myalgic encephalitis (CFS/ME), fibromyalgia (FM), and postural orthostatic tachycardia syndrome (POTS). Subsequent discussion will provide a rationale for Sleep Medicine pharmacotherapeutic options for the treatment of sleep disturbances in PASC, with specific reviews of melatonin, prazosin, stimulants (including methylphenidate, dextroamphetamine, lisdexamfetamine, and modafinil), ɣ-aminobutyric acid (GABA)ergic drugs (sodium oxybate and baclofen), and serotonergic drugs (including fluvoxamine, sertraline, and vortioxetine).

Recent Findings

Current studies suggest multifactorial involvement for PASC, with neuroinflammation, hypercoagulability, and latent reactivation of dormant viruses likely playing a role. Symptoms range in severity from mild fatigue to significant debilitation. Sleep disorders and fatigue are prominent symptoms of PASC. Poor sleep quality has been associated with increased severity of psychiatric symptoms, including anxiety, depression, and post-traumatic stress disorder symptoms. Since there is a dearth of treatment options for these patients, it behooves health care providers to find novel remedies to alleviate suffering and health care expenditures for this small but growing segment of the population.

Summary

Fatigue and sleep disturbances have been some of the most cited symptoms for patients with PASC. Significant research has highlighted a high degree of synchrony and/or comorbidity with several other clinical conditions that may share similar pathologies and are associated with disturbed sleep, including sleep deprivation, circadian disturbances, CFS/ME, FM, POTS, and RLS. The sleep medicine community may be able to offer novel options to mitigate the debilitating effects of PASC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
€32.70 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (France)

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References 

  1. Joan B Soriano MA, Carine Alsokhn, Nisreen A Alwan, , Lisa Askie HED, Janet V Diaz, Tarun Dua, Wouter de Groote, Robert Jakob, Marta , Lado JM, Srin Murthy, Jacobus Preller, Pryanka Relan, Nicoline Schiess, Archana , Seahwag. A clinical case definition of post COVID-19 condition by a Delphi consensus, 6 October 2021: World Health Organization 2021.

  2. Post COVID-19 condition (long-COVID). Government of Canada, 2022. at https://www.canada.ca/en/public-health/services/diseases/2019-novel-coronavirus-infection/symptoms/post-covid-19-condition.html#s.)

  3. Long-COVID or Post-COVID conditions. 2022. at https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects/index.html.)

  4. Alkodaymi MS, Omrani OA, Fawzy NA, et al. Prevalence of post-acute COVID-19 syndrome symptoms at different follow-up periods: a systematic review and meta-analysis. Clin Microbiol Infect. 2022;28:657–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Nalbandian A, Sehgal K, Gupta A, et al. Post-acute COVID-19 syndrome. Nat Med. 2021;27:601–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Chen LYC, Biggs CM, Jamal S, Stukas S, Wellington CL, Sekhon MS. Soluble interleukin-6 receptor in the COVID-19 cytokine storm syndrome. Cell Rep Med. 2021;2:100269.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Mizrahi B, Sudry T, Flaks-Manov N, et al. Long-COVID outcomes at one year after mild SARS-CoV-2 infection: nationwide cohort study. BMJ. 2023;380:e072529.

  8. Thaweethai T, Jolley SE, Karlson EW, et al. Development of a definition of postacute sequelae of SARS-CoV-2 infection. JAMA. 2023;329:1934–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Davis HE, McCorkell L, Vogel JM, Topol EJ. Long-COVID: major findings, mechanisms and recommendations. Nat Rev Microbiol 2023:1–14.

  10. Badenoch JB, Rengasamy ER, Watson C, et al. Persistent neuropsychiatric symptoms after COVID-19: a systematic review and meta-analysis. Brain Commun. 2022;4:fcab297.

    Article  PubMed  Google Scholar 

  11. Wong TL, Weitzer DJ. Long-COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)-a systemic review and comparison of clinical presentation and symptomatology. Medicina (Kaunas) 2021;57.

  12. Pinzon RT, Wijaya VO, Jody AA, Nunsio PN, Buana RB. Persistent neurological manifestations in long COVID-19 syndrome: a systematic review and meta-analysis. J Infect Public Health. 2022;15:856–69.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Diem L, Fregolente-Gomes L, Warncke JD, et al. Fatigue in post-COVID-19 syndrome: clinical phenomenology, comorbidities and association with initial course of COVID-19. J Cent Nerv Syst Dis. 2022;14:11795735221102728.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Cotler J, Holtzman C, Dudun C, Jason LA. A brief questionnaire to assess post-exertional malaise. Diagnostics (Basel) 2018;8.

  15. Kedor C, Freitag H, Meyer-Arndt L, et al. A prospective observational study of post-COVID-19 chronic fatigue syndrome following the first pandemic wave in Germany and biomarkers associated with symptom severity. Nat Commun. 2022;13:5104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. McNaughton CD, Austin PC, Sivaswamy A, et al. Post-acute health care burden after SARS-CoV-2 infection: a retrospective cohort study. CMAJ. 2022;194:E1368–76.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Crook H, Raza S, Nowell J, Young M, Edison P. Long covid-mechanisms, risk factors, and management. BMJ. 2021;374:n1648.

    Article  PubMed  Google Scholar 

  18. Khazaal S, Harb J, Rima M, et al. The pathophysiology of Long-COVID throughout the renin-angiotensin system. Molecules 2022;27.

  19. Kell DB, Laubscher GJ, Pretorius E. A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications. Biochem J. 2022;479:537–59.

    Article  CAS  PubMed  Google Scholar 

  20. Pretorius E, Venter C, Laubscher GJ, et al. Prevalence of symptoms, comorbidities, fibrin amyloid microclots and platelet pathology in individuals with Long COVID/Post-Acute Sequelae of COVID-19 (PASC). Cardiovasc Diabetol. 2022;21:148.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Buja LM, Wolf DA, Zhao B, et al. The emerging spectrum of cardiopulmonary pathology of the coronavirus disease 2019 (COVID-19): report of 3 autopsies from Houston, Texas, and review of autopsy findings from other United States cities. Cardiovasc Pathol. 2020;48:107233.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Pretorius E, Vlok M, Venter C, et al. Persistent clotting protein pathology in Long COVID/post-acute sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin. Cardiovasc Diabetol. 2021;20:172.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wostyn P. COVID-19 and chronic fatigue syndrome: is the worst yet to come? Med Hypotheses. 2021;146:110469.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Tarasoff-Conway JM, Carare RO, Osorio RS, et al. Clearance systems in the brain-implications for Alzheimer disease. Nat Rev Neurol. 2015;11:457–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Efstathiou V, Stefanou MI, Demetriou M, et al. Long-COVID and neuropsychiatric manifestations (Review). Exp Ther Med. 2022;23:363.

  26. Su Y, Yuan D, Chen DG, et al. Multiple early factors anticipate post-acute COVID-19 sequelae. Cell. 2022;185(881–95):e20.

    Google Scholar 

  27. Subramanian A, Nirantharakumar K, Hughes S, et al. Symptoms and risk factors for long-COVID in non-hospitalized adults. Nat Med. 2022;28:1706–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Mahase E. Covid-19: Vaccinated people are less likely to get Long-COVID, review finds. BMJ. 2022;376:o407.

  29. Antonelli M, Penfold RS, Merino J, et al. Risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app: a prospective, community-based, nested, case-control study. Lancet Infect Dis. 2022;22:43–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Al-Aly Z, Bowe B, Xie Y. Long-COVID after breakthrough SARS-CoV-2 infection. Nat Med. 2022;28:1461–7.

  31. Taquet M, Dercon Q, Harrison PJ. Six-month sequelae of post-vaccination SARS-CoV-2 infection: a retrospective cohort study of 10,024 breakthrough infections. Brain Behav Immun. 2022;103:154–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Sarkanen TO, Alakuijala APE, Dauvilliers YA, Partinen MM. Incidence of narcolepsy after H1N1 influenza and vaccinations: systematic review and meta-analysis. Sleep Med Rev. 2018;38:177–86.

    Article  PubMed  Google Scholar 

  33. Mahamid A, Bornstein RJ, Amir H. Pfizer/BioNTech SARS-CoV-2 vaccine as a potential trigger for the development of narcolepsy: a case report. J Clin Sleep Med. 2022;18:2503–6.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Wu M, Li SX, Xue P, Zhou J, Tang X. COVID-19 vaccine could trigger the relapse of secondary hypersomnia. Nat Sci Sleep. 2021;13:2267–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Moura AEF, Oliveira DN, Torres DM, et al. Central hypersomnia and chronic insomnia: expanding the spectrum of sleep disorders in long-COVID syndrome - a prospective cohort study. BMC Neurol. 2022;22:417.

  36. Evans RA, McAuley H, Harrison EM, et al. Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study. Lancet Respir Med. 2021;9:1275–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Merikanto I, Dauvilliers Y, Chung F, et al. Sleep symptoms are essential features of Long-COVID - comparing healthy controls with COVID-19 cases of different severity in the international COVID sleep study (ICOSS-II). J Sleep Res 2022:e13754.

  38. Nowakowski S, Kokonda M, Sultana R, et al. Association between sleep quality and mental health among patients at a Post-COVID-19 recovery clinic. Brain Sci 2022;12.

  39. Davis HE, Assaf GS, McCorkell L, et al. Characterizing long-COVID in an international cohort: 7 months of symptoms and their impact. EClinicalMedicine. 2021;38:101019.

  40. Scarpelli S, De Santis A, Alfonsi V, et al. The role of sleep and dreams in long-COVID. J Sleep Res 2022:e13789.

  41. Wild CJ, Nichols ES, Battista ME, Stojanoski B, Owen AM. Dissociable effects of self-reported daily sleep duration on high-level cognitive abilities. Sleep 2018;41.

  42. Wild CJ, Norton L, Menon DK, Ripsman DA, Swartz RH, Owen AM. Disentangling the cognitive, physical, and mental health sequelae of COVID-19. Cell Rep Med. 2022;3:100750.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Haack M, Sanchez E, Mullington JM. Elevated inflammatory markers in response to prolonged sleep restriction are associated with increased pain experience in healthy volunteers. Sleep. 2007;30:1145–52.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Tate W, Walker M, Sweetman E, et al. Molecular Mechanisms of neuroinflammation in ME/CFS and Long-COVID to sustain disease and promote relapses. Front Neurol. 2022;13:877772.

  45. Nunes JM, Kruger A, Proal A, Kell DB, Pretorius E. The occurrence of hyperactivated platelets and fibrinaloid microclots in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Pharmaceuticals (Basel) 2022;15.

  46. Bragee B, Michos A, Drum B, Fahlgren M, Szulkin R, Bertilson BC. Signs of intracranial hypertension, hypermobility, and craniocervical obstructions in patients with myalgic encephalomyelitis/chronic fatigue syndrome. Front Neurol. 2020;11:828.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Higgins JNP, Pickard JD, Lever AML. Chronic fatigue syndrome and idiopathic intracranial hypertension: different manifestations of the same disorder of intracranial pressure? Med Hypotheses. 2017;105:6–9.

    Article  PubMed  Google Scholar 

  48. Silva MTT, Lima MA, Torezani G, et al. Isolated intracranial hypertension associated with COVID-19. Cephalalgia. 2020;40:1452–8.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Wolfe F, Clauw DJ, Fitzcharles MA, et al. 2016 Revisions to the 2010/2011 fibromyalgia diagnostic criteria. Semin Arthritis Rheum. 2016;46:319–29.

    Article  PubMed  Google Scholar 

  50. Ursini F, Ciaffi J, Mancarella L, et al. Fibromyalgia: a new facet of the post-COVID-19 syndrome spectrum? Results from a web-based survey. RMD Open 2021;7.

  51. Siracusa R, Paola RD, Cuzzocrea S, Impellizzeri D. Fibromyalgia: pathogenesis, mechanisms, diagnosis and treatment options update. Int J Mol Sci 2021;22.

  52. Ciccone DS, Natelson BH. Comorbid illness in women with chronic fatigue syndrome: a test of the single syndrome hypothesis. Psychosom Med. 2003;65:268–75.

    Article  PubMed  Google Scholar 

  53. Natelson BH, Vu D, Coplan JD, et al. Elevations of ventricular lactate levels occur in both chronic fatigue syndrome and fibromyalgia. Fatigue. 2017;5:15–20.

    PubMed  PubMed Central  Google Scholar 

  54. Choy EH. The role of sleep in pain and fibromyalgia. Nat Rev Rheumatol. 2015;11:513–20.

    Article  PubMed  Google Scholar 

  55. Spaeth M, Rizzi M, Sarzi-Puttini P. Fibromyalgia and sleep. Best Pract Res Clin Rheumatol. 2011;25:227–39.

    Article  PubMed  Google Scholar 

  56. Maksoud R, Eaton-Fitch N, Matula M, Cabanas H, Staines D, Marshall-Gradisnik S. Systematic Review of sleep characteristics in myalgic encephalomyelitis/chronic fatigue syndrome. Healthcare (Basel) 2021;9.

  57. Vijayan S, Klerman EB, Adler GK, Kopell NJ. Thalamic mechanisms underlying alpha-delta sleep with implications for fibromyalgia. J Neurophysiol. 2015;114:1923–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Van Hoof E, De Becker P, Lapp C, Cluydts R, De Meirleir K. Defining the occurrence and influence of alpha-delta sleep in chronic fatigue syndrome. Am J Med Sci. 2007;333:78–84.

    Article  PubMed  Google Scholar 

  59. Moldofsky H, Inhaber NH, Guinta DR, Alvarez-Horine SB. Effects of sodium oxybate on sleep physiology and sleep/wake-related symptoms in patients with fibromyalgia syndrome: a double-blind, randomized, placebo-controlled study. J Rheumatol. 2010;37:2156–66.

    Article  CAS  PubMed  Google Scholar 

  60. Mahowald ML, Mahowald MW. Nighttime sleep and daytime functioning (sleepiness and fatigue) in less well-defined chronic rheumatic diseases with particular reference to the “alpha-delta NREM sleep anomaly.” Sleep Med. 2000;1:195–207.

    Article  CAS  PubMed  Google Scholar 

  61. Stone KC, Taylor DJ, McCrae CS, Kalsekar A, Lichstein KL. Nonrestorative sleep. Sleep Med Rev. 2008;12:275–88.

    Article  PubMed  Google Scholar 

  62. Diaz-Piedra C, Di Stasi LL, Baldwin CM, Buela-Casal G, Catena A. Sleep disturbances of adult women suffering from fibromyalgia: a systematic review of observational studies. Sleep Med Rev. 2015;21:86–99.

    Article  PubMed  Google Scholar 

  63. Goyal A, Saxena K, Kar A, et al. Sleep EEG signatures in COVID-19 survivors. Sleep Vigil. 2021;5:281–8.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Korszun A. Sleep and circadian rhythm disorders in fibromyalgia. Curr Rheumatol Rep. 2000;2:124–30.

    Article  CAS  PubMed  Google Scholar 

  65. Pedersen M, Ekstedt M, Smastuen MC, et al. Sleep-wake rhythm disturbances and perceived sleep in adolescent chronic fatigue syndrome. J Sleep Res. 2017;26:595–601.

    Article  PubMed  Google Scholar 

  66. McCarthy MJ. Circadian rhythm disruption in myalgic encephalomyelitis/chronic fatigue syndrome: implications for the post-acute sequelae of COVID-19. Brain Behav Immun Health. 2022;20:100412.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Merikanto I, Kortesoja L, Benedict C, et al. Evening-types show highest increase of sleep and mental health problems during the COVID-19 pandemic-multinational study on 19 267 adults. Sleep 2022;45.

  68. Plekhanova T, Rowlands AV, Evans RA, et al. Device-assessed sleep and physical activity in individuals recovering from a hospital admission for COVID-19: a multicentre study. Int J Behav Nutr Phys Act. 2022;19:94.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Merikanto I, Dauvilliers Y, Chung F, et al. Disturbances in sleep, circadian rhythms and daytime functioning in relation to coronavirus infection and Long-COVID - A multinational ICOSS study. J Sleep Res. 2022;31:e13542.

    Article  PubMed  Google Scholar 

  70. Larsen NW, Stiles LE, Shaik R, et al. Characterization of autonomic symptom burden in long-COVID: A global survey of 2,314 adults. Front Neurol. 2022;13:1012668.

  71. van Campen C, Rowe PC, Verheugt FWA, Visser FC. Numeric rating scales show prolonged post-exertional symptoms after orthostatic testing of adults with myalgic encephalomyelitis/chronic fatigue syndrome. Front Med (Lausanne). 2020;7:602894.

    Article  PubMed  Google Scholar 

  72. van Campen C, Visser FC. Orthostatic intolerance in Long-Haul COVID after SARS-CoV-2: a case-control comparison with post-EBV and Insidious-onset myalgic encephalomyelitis/chronic fatigue syndrome patients. Healthcare (Basel) 2022;10.

  73. Morrow AK, Malone LA, Kokorelis C, et al. Long-Term COVID 19 sequelae in adolescents: the overlap with orthostatic intolerance and ME/CFS. Curr Pediatr Rep. 2022;10:31–44.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Dani M, Dirksen A, Taraborrelli P, et al. Autonomic dysfunction in ‘Long-COVID’: rationale, physiology and management strategies. Clin Med (Lond). 2021;21:e63–7.

  75. Vernino S, Bourne KM, Stiles LE, et al. Postural orthostatic tachycardia syndrome (POTS): state of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting - Part 1. Auton Neurosci. 2021;235:102828.

    Article  PubMed  PubMed Central  Google Scholar 

  76. van Campen C, Verheugt FWA, Rowe PC, Visser FC. Cerebral blood flow is reduced in ME/CFS during head-up tilt testing even in the absence of hypotension or tachycardia: a quantitative, controlled study using Doppler echography. Clin Neurophysiol Pract. 2020;5:50–8.

    Article  PubMed  Google Scholar 

  77. Li H, Yu X, Liles C, et al. Autoimmune basis for postural tachycardia syndrome. J Am Heart Assoc. 2014;3:e000755.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Allen RP, Picchietti DL, Garcia-Borreguero D, et al. Restless legs syndrome/Willis-Ekbom disease diagnostic criteria: updated International Restless Legs Syndrome Study Group (IRLSSG) consensus criteria–history, rationale, description, and significance. Sleep Med. 2014;15:860–73.

    Article  PubMed  Google Scholar 

  79. Weinstock LB, Brook JB, Walters AS, Goris A, Afrin LB, Molderings GJ. Restless legs syndrome is associated with long-COVID in women. J Clin Sleep Med. 2022;18:1413–8.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Fine JS, Ambrose AF, Didehbani N, et al. Multi-disciplinary collaborative consensus guidance statement on the assessment and treatment of cognitive symptoms in patients with post-acute sequelae of SARS-CoV-2 infection (PASC). PM R. 2022;14:96–111.

    Article  PubMed  Google Scholar 

  81. Cheng AL, Anderson J, Didehbani N, et al. Multi-disciplinary collaborative consensus guidance statement on the assessment and treatment of mental health symptoms in patients with post-acute sequelae of SARS-CoV-2 infection (PASC). PM R. 2023;15:1588–604.

    Article  PubMed  Google Scholar 

  82. Herrera JE, Niehaus WN, Whiteson J, et al. Multidisciplinary collaborative consensus guidance statement on the assessment and treatment of fatigue in postacute sequelae of SARS-CoV-2 infection (PASC) patients. PM R. 2021;13:1027–43.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Artigas L, Coma M, Matos-Filipe P, et al. In-silico drug repurposing study predicts the combination of pirfenidone and melatonin as a promising candidate therapy to reduce SARS-CoV-2 infection progression and respiratory distress caused by cytokine storm. PLoS ONE. 2020;15:e0240149.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Peng Z, Zhang W, Qiao J, He B. Melatonin attenuates airway inflammation via SIRT1 dependent inhibition of NLRP3 inflammasome and IL-1beta in rats with COPD. Int Immunopharmacol. 2018;62:23–8.

    Article  CAS  PubMed  Google Scholar 

  85. Cecon E, Fernandois D, Renault N, et al. Melatonin drugs inhibit SARS-CoV-2 entry into the brain and virus-induced damage of cerebral small vessels. Cell Mol Life Sci. 2022;79:361.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Romero A, Ramos E, Lopez-Munoz F, Gil-Martin E, Escames G, Reiter RJ. Coronavirus disease 2019 (COVID-19) and Its neuroinvasive capacity: is it time for melatonin? Cell Mol Neurobiol. 2022;42:489–500.

    Article  CAS  PubMed  Google Scholar 

  87. Cardinali DP, Brown GM, Pandi-perumal SR. Possible application of melatonin in Long-COVID. Biomolecules. 2022;12:1646.

  88. Green EA, Black BK, Biaggioni I, et al. Melatonin reduces tachycardia in postural tachycardia syndrome: a randomized, crossover trial. Cardiovasc Ther. 2014;32:105–12.

    Article  CAS  PubMed  Google Scholar 

  89. Hemati K, Amini Kadijani A, Sayehmiri F, et al. Melatonin in the treatment of fibromyalgia symptoms: a systematic review. Complement Ther Clin Pract. 2020;38:101072.

    Article  PubMed  Google Scholar 

  90. Morris G, Puri BK, Walker AJ, et al. Myalgic encephalomyelitis/chronic fatigue syndrome: From pathophysiological insights to novel therapeutic opportunities. Pharmacol Res. 2019;148:104450.

    Article  CAS  PubMed  Google Scholar 

  91. Valiensi SM, Folgueira A, Vera VA, Gonzalez Cardozo A, Cardinali DP, Rugiero M. [Pre-pandemic melatonin treatment for sleep disorders and COVID-19 infection. A retrospective cross-sectional study]. Vertex 2022;XXXIII:13–24.

  92. Morgenthaler TI, Auerbach S, Casey KR, et al. Position paper for the treatment of nightmare disorder in adults: an American Academy of Sleep Medicine Position Paper. J Clin Sleep Med. 2018;14:1041–55.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Zhang Y, Ren R, Sanford LD, et al. The effects of prazosin on sleep disturbances in post-traumatic stress disorder: a systematic review and meta-analysis. Sleep Med. 2020;67:225–31.

    Article  PubMed  Google Scholar 

  94. Staedtke V, Bai RY, Kim K, et al. Disruption of a self-amplifying catecholamine loop reduces cytokine release syndrome. Nature. 2018;564:273–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Konig MF, Powell M, Staedtke V, et al. Preventing cytokine storm syndrome in COVID-19 using alpha-1 adrenergic receptor antagonists. J Clin Invest. 2020;130:3345–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Thorpy MJ, Bogan RK. Update on the pharmacologic management of narcolepsy: mechanisms of action and clinical implications. Sleep Med. 2020;68:97–109.

    Article  PubMed  Google Scholar 

  97. Faraone SV. The pharmacology of amphetamine and methylphenidate: relevance to the neurobiology of attention-deficit/hyperactivity disorder and other psychiatric comorbidities. Neurosci Biobehav Rev. 2018;87:255–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Rowe PC, Underhill RA, Friedman KJ, et al. Myalgic encephalomyelitis/chronic fatigue syndrome diagnosis and management in young people: a primer. Front Pediatr. 2017;5:121.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Randall DC, Cafferty FH, Shneerson JM, Smith IE, Llewelyn MB, File SE. Chronic treatment with modafinil may not be beneficial in patients with chronic fatigue syndrome. J Psychopharmacol. 2005;19:647–60.

    Article  CAS  PubMed  Google Scholar 

  100. Wells R, Elliott AD, Mahajan R, et al. Efficacy of therapies for postural tachycardia syndrome: a systematic review and meta-analysis. Mayo Clin Proc. 2018;93:1043–53.

    Article  PubMed  Google Scholar 

  101. Kallweit U, Bassetti CL. Pharmacological management of narcolepsy with and without cataplexy. Expert Opin Pharmacother. 2017;18:809–17.

    Article  CAS  PubMed  Google Scholar 

  102. Scharf MB, Baumann M, Berkowitz DV. The effects of sodium oxybate on clinical symptoms and sleep patterns in patients with fibromyalgia. J Rheumatol. 2003;30:1070–4.

    CAS  PubMed  Google Scholar 

  103. Russell JI, Holman AJ, Swick TJ, et al. Sodium oxybate reduces pain, fatigue, and sleep disturbance and improves functionality in fibromyalgia: results from a 14-week, randomized, double-blind, placebo-controlled study. Pain. 2011;152:1007–17.

    Article  CAS  PubMed  Google Scholar 

  104. Russell IJ, Perkins AT, Michalek JE, Oxybate SXBFSSG. Sodium oxybate relieves pain and improves function in fibromyalgia syndrome: a randomized, double-blind, placebo-controlled, multicenter clinical trial. Arthritis Rheum. 2009;60:299–309.

    Article  CAS  PubMed  Google Scholar 

  105. Spitzer AR, Broadman M. Treatment of the narcoleptiform sleep disorder in chronic fatigue syndrome and fibromyalgia with sodium oxybate. Pain Pract. 2010;10:54–9.

    Article  PubMed  Google Scholar 

  106. Abad VC, Guilleminault C. New developments in the management of narcolepsy. Nat Sci Sleep. 2017;9:39–57.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Abad VC. An evaluation of sodium oxybate as a treatment option for narcolepsy. Expert Opin Pharmacother. 2019;20:1189–99.

    Article  CAS  PubMed  Google Scholar 

  108. Mamelak M. Sleep, narcolepsy, and sodium oxybate. Curr Neuropharmacol. 2022;20:272–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Swick TJ. Sodium oxybate: a potential new pharmacological option for the treatment of fibromyalgia syndrome. Ther Adv Musculoskelet Dis. 2011;3:167–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Moldofsky H, Scarisbrick P, England R, Smythe H. Musculosketal symptoms and non-REM sleep disturbance in patients with “fibrositis syndrome” and healthy subjects. Psychosom Med. 1975;37:341–51.

    Article  CAS  PubMed  Google Scholar 

  111. Roehrs T, Hyde M, Blaisdell B, Greenwald M, Roth T. Sleep loss and REM sleep loss are hyperalgesic. Sleep. 2006;29:145–51.

    Article  PubMed  Google Scholar 

  112. Morse AM, Kelly-Pieper K, Kothare SV. Management of excessive daytime sleepiness in narcolepsy with baclofen. Pediatr Neurol. 2019;93:39–42.

    Article  PubMed  Google Scholar 

  113. Ma Y, Li S, Yang H, et al. Effect of psychotropics on the risk of COVID-19 in middle-aged and older adults. Eur Neuropsychopharmacol. 2022;66:67–77.

    Article  PubMed  PubMed Central  Google Scholar 

  114. Lee CH, Giuliani F. The role of inflammation in depression and fatigue. Front Immunol. 2019;10:1696.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Kohler CA, Freitas TH, Stubbs B, et al. Peripheral alterations in cytokine and chemokine levels after antidepressant drug treatment for major depressive disorder: systematic review and meta-analysis. Mol Neurobiol. 2018;55:4195–206.

    CAS  PubMed  Google Scholar 

  116. Xiao X, Wang C, Chang D, et al. Identification of potent and safe antiviral therapeutic candidates against SARS-CoV-2. Front Immunol. 2020;11:586572.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Lenze EJ, Mattar C, Zorumski CF, et al. Fluvoxamine vs placebo and clinical deterioration in outpatients with symptomatic COVID-19: a randomized clinical trial. JAMA. 2020;324:2292–300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Wong AC, Devason AS, Umana IC, et al. Serotonin reduction in post-acute sequelae of viral infection. Cell. 2023;186(4851–67):e20.

    Google Scholar 

  119. Ceban F, Leber A, Jawad MY, et al. Registered clinical trials investigating treatment of long-COVID: a scoping review and recommendations for research. Infect Dis (Lond). 2022;54:467–77.

Download references

Author information

Authors and Affiliations

  1. Sleep Research Unit, Department of Psychiatry, Institute for Mental Health Research, University of Ottawa, Ottawa, ON, Canada

    Elliott K Lee

  2. Mayo Center for Sleep Medicine, Department of Psychiatry & Psychology, Mayo Clinic College of Medicine, Rochester, MN, USA

    R. Robert Auger

Authors
  1. Elliott K Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Robert Auger
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

EKL wrote the main manuscript and table. RRA contributed to the editing and analysis of literature. All authors reviewed the manuscript.

Corresponding author

Correspondence to Elliott K Lee.

Ethics declarations

Competing interests

The authors declare no competing interests.

Conflict of Interest

The authors declare no competing interest.

Human and Animal Rights and Informed Consent

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, E.K., Auger, R.R. Sleep and Long COVID—A Review and Exploration of Sleep Disturbances in Post Acute Sequelae of SARS-COV-2 (PASC) and Therapeutic Possibilities. Curr Sleep Medicine Rep 10, 169–180 (2024). https://doi.org/10.1007/s40675-024-00299-4

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40675-024-00299-4

Keywords

Search

Navigation