Living Evidence - post acute sequelae of COVID-19 (long COVID)

Living evidence tables provide high level summaries of key studies and evidence on a particular topic, and links to sources. They are reviewed regularly and updated as new evidence and information is published.


Most people with COVID-19 will recover completely within a few weeks. However, some may keep experiencing symptoms for weeks or months after their diagnosis. This is called "long COVID", "post-acute sequelae of SARS-CoV-2" or "post COVID-19 condition".


  • The Australian National Clinical Evidence Taskforce defines long COVID as “signs and symptoms that develop during or after an infection consistent with COVID-19, continue for more than 12 weeks and are not explained by an alternative diagnosis. It usually presents with clusters of symptoms, often overlapping, which can fluctuate and change over time and can affect any system in the body. Post COVID-19 condition may be considered before 12 weeks while the possibility of an alternative underlying disease is also being assessed.”1
  • The World Health Organization has also published specific information on the definition and nature of long COVID in children and adolescents.2


  • The definition of long COVID varies considerably across studies. Researchers have called for consensus in definitions.3, 4
  • Methods of data collection vary. The prevalence of long COVID in self-report longitudinal studies versus evidence of long COVID documented in electronic health records can be substantially different.^5, 6
  • Recent studies have confounds associated with variants, vaccines and reinfection history. When studies pool data across subgroups, it is difficult to tease apart the role of different variables on long COVID.
  • Uncertainty intervals around result estimates are wide in long COVID studies, reflecting as yet limited and heterogeneous data.7

Regular checks are conducted for new content and any updates are highlighted.



Symptoms may:

  • range from mild to severe
  • be singular or multiple
  • be continuous or episodic
  • symptoms can fluctuate or even increase in severity throughout the course of long-COVID.8

More than 200 persistent symptoms of COVID-19 have been reported in the literature.9 Only commonly reported and emerging symptoms have been included here.

  • Respiratory symptoms7
    • shortness of breath or difficulty breathing
    • persistent cough
    • chest pain or discomfort
  • Generalised symptoms7, 10, 11
    • fatigue
    • weakness, effort intolerance, post exertional malaise
    • rash and hair loss
    • general pain
  • Cardiovascular symptoms12, 13
    • chest tightness and pain
    • cardiac symptoms, including chest pain, primary arrhythmia, palpitations, dyspnoea on exertion.
    • Autonomic dysfunction including postural orthostatic tachycardia syndrome
  • Neurological symptoms11, 14
    • cognitive impairment including memory loss, concentration difficulties and brain fog
    • loss of smell or taste
    • headache
  • Gastrointestinal symptoms15, 16
    • irritable bowel syndrome
    • diarrhoea, constipation, abdominal pain, nausea/vomiting and heartburn
  • Musculoskeletal symptoms
    • musculoskeletal pain17
    • muscle weakness18
  • Psychological / psychiatric symptoms19
    • anxiety
    • depression
    • insomnia
    • psychotic disorders
  • Other
    • kidney outcomes20

There are a number of chronic sequelae of severe acute COVID-19 disease that might lead to persistent impairment and may result in chronic disease:

  • pulmonary fibrosis secondary to acute lung injury21
  • myocarditis which may lead to persistent cardiac dysfunction22
  • pulmonary thromboemboli23
  • diabetes24, 25
  • cardiovascular disease12
  • dyslipidaemia26

Symptoms in children and adolescents are typically similar.27, 28


Recent prevalence estimates from larger and more rigorous studies (adults or all ages):

  • Recent Victorian long COVID prevalence estimates for long COVID morbidity among adults with symptomatic infections range from 0.17% to 4.4%. The prevalence is lower among vaccinated adults who were infected with the Omicron variant (0.09% for non-hospitalised and 1.9% for hospitalised adults).29
  • A global systematic analysis included data for 1.2 million individuals from 22 countries who had COVID-19 in 2020 and 2021 presented modelled prevalence estimates as follows:
    • 6.17% of symptomatic COVID-19 patients who survived their acute episode experienced at least one of three long COVID symptom clusters (fatigue, cognitive and respiratory) at three months after symptom onset.
    • Twelve months after symptom onset, this prevalence decreased to 0.9%.7
  • A systematic review noted that studies with the lowest risk of bias and with community-based samples estimated the absolute risk difference between cases and controls to be between 1% to 9% (mean 4.8%).30
  • Large cohort studies of pre-Omicron variants, with PCR-negative control groups report:
    • Israel - Patients with mild initial infections have an increased risk for a small number of health outcomes (6 out of 70 outcomes) at up to one year follow-up compared to the controls with no infection history. At 180-360 days, the risk difference per 10,000 patients for these six outcomes ranged from 8.3 to 50.2.31
    • Scotland - At six and 12 months, one or more symptom was reported by 71.5% and 70.7% respectively of those previously infected, compared with 53.5% and 56.5% of those never infected. Altered taste, smell and confusion improved over time compared to the never infected group.32

Effect of variant

  • Studies suggest lower prevalence of long COVID following infection with Omicron than with Delta, especially among double vaccinated individuals and irrespective of time elapsed between infection and most recent vaccination. 33, 34


  • In children, COVID-19 infection (pre-Omicron) was associated with an increased risk of reporting at least one symptom lasting more than two months than controls (absolute risk difference: 12.8% for 0-3 years; 4.4% for 4-11 years; 4.7% for 12-14 years).35
  • Prevalence of long COVID in children and adolescents is around 3.7%, specifically 1.7% in non-hospitalised children but up to 5.2% in hospitalised children, at three months post infection. At six-month follow-up, the symptom prevalence in adolescents with an infection history is comparable to the symptom prevalence in adolescents without a history of infection.36, 37


There is a higher chance of recovery during the first year following acute infection.38

A global systematic analysis identified that:

  • Median duration of long COVID in community infections was 4.0 months.
  • Median duration of long COVID in hospitalised cases was 9.0 months.
  • In individuals with long COVID, 15.1% of patients continued to experience symptoms 12 months after acute infection.7

Protective and risk factors

Protective factors:

  • vaccination39-41
  • young age42
  • antivirals43-45
  • treatment with monoclonal antibodies46
  • sleep quality pre-infection47

Risk factors for long COVID are likely multifactorial and interrelated and include: older age, being female, higher weight, co-morbidities (including anxiety, depression, asthma, chronic kidney disease, chronic obstructive pulmonary disease, diabetes, immunosuppression, and ischaemic heart disease), previous hospitalisation with COVID-19.48, 49

Reinfection has been associated with an increased risk of death, hospitalisation, and sequelae in multiple organ systems, compared to no reinfection, especially in patients older than 55.50 However, the risk of new-onset long Covid after a second SARS-CoV-2 infection is lower than that after a first infection for those ≥16 years.^51

Mechanisms / Aetiology

Little is known about the underlying cause of long COVID, as per most post-acute infection syndromes.52

Two overarching mechanisms have been proposed to explain the underlying pathophysiology of long COVID: organ damage from the initial acute infection phase, and long-term inflammatory mechanisms.53-55

Differential diagnosis and assessment

In clinical settings, there are no definitive test for long COVID, and diagnosis is based on differential diagnosis.56, 57

Guidance on assessment for long COVID has been published by the

  • Australian National COVID-19 Clinical Evidence Taskforce1
  • National Institute for Health and Care Excellence (NICE) 56

Guidelines advocate for a holistic, person-centred approach to diagnosis.58


Management of long COVID is evolving and is based on the management of symptoms. The evidence-base for managing long COVID is low quality, with very few randomised control trials published yet.59

Guidance or recommendations on management for long COVID have been published by the:

  • Australian National COVID-19 Clinical Evidence Taskforce1
  • National Institute for Health and Care Excellence (NICE)56

The mainstay of management is supportive, holistic care, symptom control, and detection of treatable complications.60

  • Self-management strategies are promoted61
  • Multidisciplinary care is promoted62
  • Symptom management is provided in primary care or referral to specialised care as required.63
  • A graded and individualised approach to exercise may be required, especially if post-exertional malaise is present.1

Pharmaceutical Treatments

As yet most pharmaceutical treatments are experimental. In a single-centre, double-blind, randomised controlled phase 2a pilot study, patients with long COVID were treated with 4 weeks of AXA1125, an orally administered endogenous metabolic modulator. Treated patients reported significant improvement in fatigue-based symptoms compared to controls.64


  1. National Clinical Evidence Taskforce COVID-19 (NCET). Australian guidelines for the clinical care of people with COVID-19: Care after COVID-19. Australia: NCET; 2023 [cited 29 Jun 2023]. Available from:
  2. World Health Organization (WHO). A clinical case definition for post COVID-19 condition in children and adolescents by expert consensus, 16 February 2023. Geneva: WHO; 2023 [cited 29 Jun 2023]. Available from:
  3. Munblit D, O'Hara ME, Akrami A, et al. Long COVID: aiming for a consensus. The Lancet Respiratory Medicine. 2022;10(7):632-4. DOI: 10.1016/S2213-2600(22)00135-7
  4. Haslam A, Olivier T, Prasad V. The definition of long COVID used in interventional studies. Eur J Clin Invest. 2023 Aug;53(8):e13989. DOI: 10.1111/eci.13989
  5. Fung KW, Baye F, Baik SH, et al. Long COVID in Elderly Patients: An Epidemiologic Exploration Using a Medicare Cohort. medRxiv. 2023:2023.02.09.23285742. DOI: 10.1101/2023.02.09.23285742
  6. Knuppel A, Boyd A, Macleod J, et al. The long COVID evidence gap: comparing self-reporting and clinical coding of long COVID using longitudinal study data linked to healthcare records. medRxiv. 2023:2023.02.10.23285717. DOI: 10.1101/2023.02.10.23285717
  7. Global Burden of Disease Long COVID Collaborators. Estimated Global Proportions of Individuals With Persistent Fatigue, Cognitive, and Respiratory Symptom Clusters Following Symptomatic COVID-19 in 2020 and 2021. JAMA. 2022;328(16):1604-15. DOI: 10.1001/jama.2022.18931
  8. Fjelltveit EB, Blomberg B, Kuwelker K, et al. Symptom Burden and Immune Dynamics 6 to 18 Months Following Mild Severe Acute Respiratory Syndrome Coronavirus 2 Infection (SARS-CoV-2): A Case-control Study. Clinical Infectious Diseases. 2022;76(3):e60-e70. DOI: 10.1093/cid/ciac655
  9. World Health Organization (WHO). Post COVID-19 condition (Long COVID). Geneva: WHO; 2022 [Available from:
  10. 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 May;28(5):657-66. DOI: 10.1016/j.cmi.2022.01.014
  11. Natarajan A, Shetty A, Delanerolle G, et al. A systematic review and meta-analysis of long COVID symptoms. Systematic Reviews. 2023 2023/05/27;12(1):88. DOI: 10.1186/s13643-023-02250-0
  12. Xie Y, Xu E, Bowe B, et al. Long-term cardiovascular outcomes of COVID-19. Nature Medicine. 2022 2022/03/01;28(3):583-90. DOI: 10.1038/s41591-022-01689-3
  13. Fedorowski A, Sutton R. Autonomic dysfunction and postural orthostatic tachycardia syndrome in post-acute COVID-19 syndrome. Nature Reviews Cardiology. 2023 2023/05/01;20(5):281-2. DOI: 10.1038/s41569-023-00842-w
  14. Patel UK, Mehta N, Patel A, et al. Long-Term Neurological Sequelae Among Severe COVID-19 Patients: A Systematic Review and Meta-Analysis. Cureus. 2022 Sep;14(9):e29694. DOI: 10.7759/cureus.29694
  15. Choudhury A, Tariq R, Jena A, et al. Gastrointestinal manifestations of long COVID: A systematic review and meta-analysis. Therap Adv Gastroenterol. 2022;15:17562848221118403. DOI: 10.1177/17562848221118403
  16. Xu E, Xie Y, Al-Aly Z. Long-term gastrointestinal outcomes of COVID-19. Nature Communications. 2023 2023/03/07;14(1):983. DOI: 10.1038/s41467-023-36223-7
  17. Fernández-de-las-Peñas C, Navarro-Santana M, Plaza-Manzano G, et al. Time course prevalence of post-COVID pain symptoms of musculoskeletal origin in patients who had survived severe acute respiratory syndrome coronavirus 2 infection: a systematic review and meta-analysis. PAIN. 2022;163(7).
  18. Silva CC, Bichara CNC, Carneiro FRO, et al. Muscle dysfunction in the long coronavirus disease 2019 syndrome: Pathogenesis and clinical approach. Rev Med Virol. 2022 Nov;32(6):e2355. DOI: 10.1002/rmv.2355
  19. Bourmistrova NW, Solomon T, Braude P, et al. Long-term effects of COVID-19 on mental health: A systematic review. J Affect Disord. 2022 Feb 15;299:118-25. DOI: 10.1016/j.jad.2021.11.031
  20. Bowe B, Xie Y, Xu E, et al. Kidney Outcomes in Long COVID. Journal of the American Society of Nephrology. 2021;32(11):2851-62. DOI: 10.1681/asn.2021060734
  21. Stewart I, Jacob J, George PM, et al. Residual Lung Abnormalities Following COVID-19 Hospitalization: Interim Analysis of the UKILD Post-COVID Study. Am J Respir Crit Care Med. 2022 Dec 1. DOI: 10.1164/rccm.202203-0564OC
  22. Haryalchi K, Olangian-Tehrani S, Asgari Galebin SM, et al. The importance of myocarditis in Covid-19. Health Science Reports. 2022;5(1):e488. DOI:
  23. Katsoularis I, Fonseca-Rodríguez O, Farrington P, et al. Risks of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19: nationwide self-controlled cases series and matched cohort study. BMJ. 2022;377:e069590. DOI: 10.1136/bmj-2021-069590
  24. Rezel-Potts E, Douiri A, Sun X, et al. Cardiometabolic outcomes up to 12 months after COVID-19 infection. A matched cohort study in the UK. PLOS Medicine. 2022;19(7):e1004052. DOI: 10.1371/journal.pmed.1004052
  25. Zhang T, Mei Q, Zhang Z, et al. Risk for newly diagnosed diabetes after COVID-19: a systematic review and meta-analysis. BMC Medicine. 2022 2022/11/15;20(1):444. DOI: 10.1186/s12916-022-02656-y
  26. Xu E, Xie Y, Al-Aly Z. Risks and burdens of incident dyslipidaemia in long COVID: a cohort study. The Lancet Diabetes & Endocrinology. 2023;11(2):120-8. DOI: 10.1016/S2213-8587(22)00355-2
  27. Lopez-Leon S, Wegman-Ostrosky T, Ayuzo del Valle NC, et al. Long-COVID in children and adolescents: a systematic review and meta-analyses. Scientific Reports. 2022 2022/06/23;12(1):9950. DOI: 10.1038/s41598-022-13495-5
  28. Pellegrino R, Chiappini E, Licari A, et al. Prevalence and clinical presentation of long COVID in children: a systematic review. Eur J Pediatr. 2022 Dec;181(12):3995-4009. DOI: 10.1007/s00431-022-04600-x
  29. Szanyi J, Wilson T, Howe S, et al. Epidemiologic and economic modelling of optimal COVID-19 policy: public health and social measures, masks and vaccines in Victoria, Australia. The Lancet Regional Health – Western Pacific. 2023;32. DOI: 10.1016/j.lanwpc.2022.100675
  30. Woodrow M, Carey C, Ziauddeen N, et al. Systematic review of the prevalence of Long Covid. Open Forum Infectious Diseases. 2023:ofad233. DOI: 10.1093/ofid/ofad233
  31. 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. DOI: 10.1136/bmj-2022-072529
  32. Hastie CE, Lowe DJ, McAuley A, et al. Natural history of long-COVID in a nationwide, population cohort study. Nature Communications. 2023 2023/06/13;14(1):3504. DOI: 10.1038/s41467-023-39193-y
  33. Antonelli M, Pujol JC, Spector TD, et al. Risk of long COVID associated with delta versus omicron variants of SARS-CoV-2. The Lancet. 2022;399(10343):2263-4. DOI: 10.1016/S0140-6736(22)00941-2
  34. Ayoubkhani D, Bosworth M. Self-reported long COVID after infection with the Omicron variant in the UK: 18 July 2022. London: Office for National Statistics; 2022 [cited 28 Jun 2023]. Available from:
  35. Kikkenborg Berg S, Palm P, Nygaard U, et al. Long COVID symptoms in SARS-CoV-2-positive children aged 0-14 years and matched controls in Denmark (LongCOVIDKidsDK): a national, cross-sectional study. The Lancet Child & Adolescent Health. 2022;6(9):614-23. DOI: 10.1016/S2352-4642(22)00154-7
  36. Kostev K, Smith L, Koyanagi A, et al. Post-COVID-19 conditions in children and adolescents diagnosed with COVID-19. Pediatric Research. 2022 2022/05/14. DOI: 10.1038/s41390-022-02111-x
  37. Funk AL, Kuppermann N, Florin TA, et al. Post–COVID-19 Conditions Among Children 90 Days After SARS-CoV-2 Infection. JAMA Network Open. 2022;5(7):e2223253-e. DOI: 10.1001/jamanetworkopen.2022.23253
  38. Marshall M. Long COVID: answers emerge on how many people get better. Nature. 2023;619(7968). DOI: 10.1038/d41586-023-02121-7
  39. Ceban F, Kulzhabayeva D, Rodrigues NB, et al. COVID-19 vaccination for the prevention and treatment of long COVID: A systematic review and meta-analysis. Brain, Behavior, and Immunity. 2023 2023/07/01/;111:211-29. DOI:
  40. Notarte KI, Catahay JA, Velasco JV, et al. Impact of COVID-19 vaccination on the risk of developing long-COVID and on existing long-COVID symptoms: A systematic review. EClinicalMedicine. 2022 Nov;53:101624. DOI: 10.1016/j.eclinm.2022.101624
  41. Marra AR, Kobayashi T, Suzuki H, et al. The effectiveness of coronavirus disease 2019 (COVID-19) vaccine in the prevention of post–COVID-19 conditions: A systematic literature review and meta-analysis. Antimicrobial Stewardship & Healthcare Epidemiology. 2022;2(1):e192. DOI: 10.1017/ash.2022.336
  42. Messiah SE, Hao T, DeSantis SM, et al. Comparison of Persistent Symptoms Following SARS-CoV-2 Infection by Antibody Status in Nonhospitalized Children and Adolescents. The Pediatric Infectious Disease Journal. 2022;41(10):e409-e17. DOI: 10.1097/inf.0000000000003653
  43. Xie Y, Choi T, Al-Aly Z. Molnupiravir and risk of post-acute sequelae of covid-19: cohort study. BMJ. 2023;381:e074572. DOI: 10.1136/bmj-2022-074572
  44. Xie Y, Choi T, Al-Aly Z. Association of Treatment With Nirmatrelvir and the Risk of Post–COVID-19 Condition. JAMA Internal Medicine. 2023;183(6):554-64. DOI: 10.1001/jamainternmed.2023.0743
  45. Liu TH, Wu JY, Huang PY, et al. The effect of nirmatrelvir-ritonavir on the long-term risk of neuropsychiatric sequelae following COVID-19. J Med Virol. 2023 Jul;95(7):e28951. DOI: 10.1002/jmv.28951
  46. Tannous J, Pan AP, Potter T, et al. Real-world effectiveness of COVID-19 vaccines and anti-SARS-CoV-2 monoclonal antibodies against postacute sequelae of SARS-CoV-2: analysis of a COVID-19 observational registry for a diverse US metropolitan population. BMJ Open. 2023 Apr 5;13(4):e067611. DOI: 10.1136/bmjopen-2022-067611
  47. Wang S, Huang T, Weisskopf MG, et al. Multidimensional Sleep Health Prior to SARS-CoV-2 Infection and Risk of Post–COVID-19 Condition. JAMA Network Open. 2023;6(5):e2315885-e. DOI: 10.1001/jamanetworkopen.2023.15885
  48. Fritsche LG, Jin W, Admon AJ, et al. Characterizing and Predicting Post-Acute Sequelae of SARS CoV-2 Infection (PASC) in a Large Academic Medical Center in the US. Journal of Clinical Medicine. 2023;12(4):1328.
  49. Tsampasian V, Elghazaly H, Chattopadhyay R, et al. Risk Factors Associated With Post−COVID-19 Condition: A Systematic Review and Meta-analysis. JAMA Internal Medicine. 2023;183(6):566-80. DOI: 10.1001/jamainternmed.2023.0750
  50. Bowe B, Xie Y, Al-Aly Z. Acute and postacute sequelae associated with SARS-CoV-2 reinfection. Nature Medicine. 2022 2022/11/01;28(11):2398-405. DOI: 10.1038/s41591-022-02051-3
  51. Bosworth ML, Shenhuy B, Walker AS, et al. Risk of new-onset Long Covid following reinfection with SARS-CoV-2: community-based cohort study. medRxiv. 2023:2023.04.13.23288522. DOI: 10.1101/2023.04.13.23288522
  52. Choutka J, Jansari V, Hornig M, et al. Unexplained post-acute infection syndromes. Nature Medicine. 2022 2022/05/01;28(5):911-23. DOI: 10.1038/s41591-022-01810-6
  53. Castanares-Zapatero D, Chalon P, Kohn L, et al. Pathophysiology and mechanism of long COVID: a comprehensive review. Ann Med. 2022 Dec;54(1):1473-87. DOI: 10.1080/07853890.2022.2076901
  54. Iwasaki A, Putrino D. Why we need a deeper understanding of the pathophysiology of long COVID. The Lancet Infectious Diseases. 2023;23(4):393-5. DOI: 10.1016/S1473-3099(23)00053-1
  55. Altmann DM, Whettlock EM, Liu S, et al. The immunology of long COVID. Nature Reviews Immunology. 2023 2023/07/11. DOI: 10.1038/s41577-023-00904-7
  56. National Institute for Health and Care Excellence (NICE). COVID-19 rapid guideline: managing the long-term effects of COVID-19. London: NICE; 2021 [cited 20 Jun 2023]. Available from:
  57. Retornaz F, Rebaudet S, Stavris C, et al. Long-term neuromuscular consequences of SARS-Cov-2 and their similarities with myalgic encephalomyelitis/chronic fatigue syndrome: results of the retrospective CoLGEM study. Journal of Translational Medicine. 2022 2022/09/24;20(1):429. DOI: 10.1186/s12967-022-03638-7
  58. Sisó-Almirall A, Brito-Zerón P, Conangla Ferrín L, et al. Long Covid-19: Proposed Primary Care Clinical Guidelines for Diagnosis and Disease Management. International Journal of Environmental Research and Public Health.
  59. Veronese N, Bonica R, Cotugno S, et al. Interventions for Improving Long COVID-19 Symptomatology: A Systematic Review. Viruses.
  60. Greenhalgh T, Sivan M, Delaney B, et al. Long covid—an update for primary care. BMJ. 2022;378:e072117. DOI: 10.1136/bmj-2022-072117
  61. Brown K, Yahyouche A, Haroon S, et al. Long COVID and self-management. The Lancet. 2022;399(10322):355. DOI: 10.1016/S0140-6736(21)02798-7
  62. Barshikar S, Laguerre M, Gordon P, et al. Integrated Care Models for Long Coronavirus Disease. Physical Medicine and Rehabilitation Clinics of North America. 2023 2023/08/01/;34(3):689-700. DOI:
  63. Wolf S, Zechmeister-Koss I, Erdös J. Possible long COVID healthcare pathways: a scoping review. BMC Health Services Research. 2022 2022/08/23;22(1):1076. DOI: 10.1186/s12913-022-08384-6
  64. Finnigan LEM, Cassar MP, Koziel MJ, et al. Efficacy and tolerability of an endogenous metabolic modulator (AXA1125) in fatigue-predominant long COVID: a single-centre, double-blind, randomised controlled phase 2a pilot study. eClinicalMedicine. 2023;59. DOI: 10.1016/j.eclinm.2023.101946


* Preliminary data, not fully established, in some cases small numbers or short follow up; interpret with caution

^ Commentary, grey literature, pre peer review or news

The "last updated" date refers to the date when the evidence was last reviewed.

Living evidence tables include some links to low quality sources and an assessment of the original source has not been undertaken. Sources are monitored regularly but due to rapidly emerging information, tables may not always reflect the most current evidence. The tables are not peer reviewed, and inclusion does not imply official recommendation nor endorsement of NSW Health.

Last updated on 8 Sep 2023

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