Yıl: 2021 Cilt: 51 Sayı: Özel Sayı 1 Sayfa Aralığı: 3284 - 3300 Metin Dili: İngilizce DOI: 10.3906/sag-2107-137 İndeks Tarihi: 26-01-2022

From asymptomatic to critical illness: decoding various clinical stages of COVID-19

Öz:
Abstract: The clinical course of COVID-19 is variable, with clinical manifestation ranging from 81% mild course to 14% severe course along with 5% critical course in patients. The asymptomatic course is reported to potentially range between 20% and 70% (avg. 33%). A more severe course is seen in the elderly, those with various chronic diseases, and the immunosuppressed, where the case fatality rate is higher in these risk groups. The disease progresses with various symptoms, such as fever, cough, shortness of breath, malaise, myalgia, taste and smell disorders, diarrhea, sore throat, headache, and conjunctivitis. The disease begins with shortness of breath, indicative of lung damage, after an average of 7 to 10 days, and progresses in ARDS, sepsis, and septic shock. Some patients quickly enter shortness of breath, while others gradually develop shortness of breath and chest tightness and burning. The risk factors for a poor prognosis are age, comorbidities, and changes in laboratory tests. Secondary bacterial and fungal infections frequently develop with steroids and immunosuppressants, especially in the intensive care unit. Frequent complications in hospitalized patients include pneumonia (75%), ARDS (15%), acute renal failure (9%), and acute liver injury (19%). An increased incidence of heart damage is observed, including acute heart failure, arrhythmias, and myocarditis. Of the patients hospitalized due to COVID-19, 10%–25% present with prothrombotic coagulopathy, resulting in venous and arterial thromboembolic events. The most common extrapulmonary symptom is neuropsychiatric involvement, frequently accompanied by insomnia, an impediment to remembering, and an altered state of consciousness. During the course of COVID-19, patients undergo some pathological changes (severe lymphopenia, high levels of C-reactive protein, D-dimer, ferritin, etc.) depending on the condition and exposure level of the affected systems as shown by various laboratory tests. The relevant tests are the guiding elements of risk assessment, clinical monitoring, disease severity, and prognosis setting and therapy decisionmaking processes.Key words: COVID-19, clinical features, risk factors, complications, laboratory tests
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  • 1. Ladhani SN. Crossing the Rubicon: A fine line between waiting and vaccinating adolescents against COVID-19. Journal of Infection. 2021;83(3):294-297. doi: 10.1016/j.jinf.2021.07.015
  • 2. Jin Y, Yang H, Ji W, Wu W, Chen S et al. Virology, epidemiology, pathogenesis, and control of COVID-19. Viruses 2020; 12 (4): E372. doi: 10.3390/v12040372
  • 3. Pascarella G, Strumia A, Piliego C, Bruno F, Del Buono R et al. COVID-19 diagnosis and management: a comprehensive review. Journal of Internal Medicine 2020; 288 (2): 192- 20610.1111/joim.13091. doi: 10.1111/joim.13091
  • 4. Wong SCY, Kwong RT, Wu TC, Chan JWM, Chu MY et al. Risk of nosocomial transmission of coronavirus disease 2019: an experience in a general ward setting in Hong Kong. Journal of Hospital Infection 2020; 105 (2): 119-127. doi: 10.1016/j. jhin.2020.03.036
  • 5. McIntosh K. COVID-19: Clinical features. In: UpToDate. Hirsch MS, Bloom A (editors), UpToDate, Waltham, MA, USA, 2021.
  • 6. Campbell F, Archer B, Laurenson-Schafer H, Jinnai Y, Konings F et al. Increased transmissibility and global spread of SARS-CoV-2 variants of concern as at June 2021, Eurosurveillance 2021; 26 (24): 2100509. doi: 10.2807/1560-7917. ES.2021.26.24.2100509
  • 7. Chan JF, Yuan S, Kok KH, To KK, Chu H et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet 2020; 395 (10223): 514-23. doi: 10.1016/S0140- 6736(20)30154-9
  • 8. Lauer SA, Grantz KH, Bi Q, Jones FK, Zheng Q et al. The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application. Annals of Internal Medicine 2020; 172 (9): 577- 582. doi: 10.7326/M20-0504
  • 9. Li Q, Guan X, Wu P, Wang X, Zhou L et al. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. The New England Journal of Medicine 2020; 382 (13): 1199-1207. doi: 10.1056/NEJMoa2001316
  • 10. Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ et al. Clinical Characteristics of Coronavirus Disease 2019 in China. The New England Journal of Medicine 2020; 382 (18): 1708-1720. doi: 10.1056/NEJMoa2002032
  • 11. Sakurai A, Sasaki T, Kato S, Hayashi M, Tsuzuki SI et al. Natural History of Asymptomatic SARS-CoV-2 Infection The New England Journal of Medicine 2020; 383 (9): 885-886. doi: 10.1056/NEJMc2013020
  • 12. Wang D, Hu B, Hu C, Zhu F, Liu X et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel CoronavirusInfected Pneumonia in Wuhan, China. JAMA: The Journal of the American Medical Association 2020; 323 (11): 1061-1069. doi: 10.1001/jama.2020.1585
  • 13. Huang C, Wang Y, Li X, Ren L, Zhao J et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395 (10223): 497-506. doi: 10.1016/S0140- 6736(20)30183-5
  • 14. Chen N, Zhou M, Dong X, Qu J, Gong F et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020; 395 (10223): 507-513. doi: 10.1016/S0140-6736(20)30211-7
  • 15. He F, Deng Y, Li W. Coronavirus disease 2019 (COVID-19): What we know? Journal of Medical Virology 2020; 92 (7): 719- 725. doi: 10.1002/jmv.25766
  • 16. Baj J, Karakuła-Juchnowicz H, Teresiński G, Buszewicz G, Ciesielka M et al. COVID-19: Specific and Non-Specific Clinical Manifestations and Symptoms: The Current State of Knowledge, Journal of Clinical Medicine 2020; 9(6): 1753. doi: 10.3390/jcm9061753
  • 17. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese center for disease control and prevention. JAMA: The Journal of the American Medical Association 2020; 323: 1239–42. doi: 10.1001/jama.2020.2648
  • 18. Mizumoto K, Kagaya K, Zarebski A, Chowell G. Estimating the asymptomatic proportion of coronavirus disease 2019 (COVID-19) cases on board the Diamond Princess cruise ship, Yokohama, Japan, 2020. Eurosurveillance 2020; 25(10): 2000180. doi: 10.2807/1560-7917.ES.2020.25.10.2000180
  • 19. Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T et al. Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA: The Journal of the American Medical Association 2020; 23 (20): 2052-2059. doi: 10.1001/ jama.2020.6775
  • 20. Cummings MJ, Baldwin MR, Abrams D, Jacobson SD, Meyer BJ et al. Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study. Lancet 2020; 395 (10239): 1763-1770. doi: 10.1016/S0140-6736(20)31189-2
  • 21. Petrilli CM, Jones SA, Yang J, Rajagopalan H, O’Donnell L et al. Factors Associated With Hospital Admission and Critical Illness Among 5279 People With Coronavirus Disease 2019 in New York City: Prospective Cohort Study. the British Medical Journal 2020; 369: m1966. doi: 10.1136/bmj.m1966
  • 22. Liu K, Chen Y, Lin R, Han K. Clinical feature of COVID-19 in elderly patients: a comparison with young and middleaged patients. Journal of Infection 2020; 80(6): e14-e18.doi: 10.1016/j.jinf.2020.03.005
  • 23. Lake MA. What we know so far: COVID-19 current clinical knowledge and research. Clinical Medicine Journal 2020; 20 (2): 124-127. doi: 10.7861/clinmed.2019-coron
  • 24. Ioannidis JPA. Reconciling estimates of global spread and infection fatality rates of COVID-19: An overview of systematic evaluations. European Journal of Clinical Investigation 2021; 51 (5): e13554. doi: 10.1111/eci.13554
  • 25. Meyerowitz-Katz G, Merone L. A systematic review and metaanalysis of published research data on COVID-19 infection fatality rates. International Journal of Infectious Diseases 2020; 101: 138-148. doi: 10.1016/j.ijid.2020.09.1464
  • 26. Grasselli G, Pesenti A, Cecconi M. Critical Care Utilization for the COVID-19 Outbreak in Lombardy, Italy: Early Experience and Forecast During an Emergency Response. JAMA: The Journal of the American Medical Association 2020; 323 (16): 1545-1546. doi: 10.1001/jama.2020.4031
  • 27. Onder G, Rezza G, Brusaferro S. Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy. JAMA: The Journal of the American Medical Association 2020; 323 (18): 1775-1776 doi: 10.1001/jama.2020.4683
  • 28. Levin AT, Hanage WP, Owusu-Boaitey N, Cochran KB, Walsh SP, Meyerowitz-Katz G. Assessing the age specificity of infection fatality rates for COVID-19: systematic review, metaanalysis, and public policy implications. European Journal of Epidemiology 2020; 35 (12): 1123-1128. doi: 10.1007/s10654- 020-00698-1
  • 29. Yang X, Yu Y, Xu J, Shu H, Xia J et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. the Lancet Respiratory Medicine 2020; 8 (5): 475-481. doi: 10.1016/S2213-2600(20)30079-5
  • 30. CDC COVID-19 Response Team. Severe Outcomes Among Patients with Coronavirus Disease 2019 (COVID-19) - United States, February 12-March 16, 2020. Morbidity and Mortality Weekly Report (MMWR) 2020; 69 (12): 343-346. doi: 10.15585/mmwr.mm6912e2
  • 31. McMichael TM, Currie DW, Clark S, Pogosjans S, Kay M et al. Epidemiology of Covid-19 in a Long-Term Care Facility in King County, Washington. The New England Journal of Medicine 2020; 382 (21): 2005-2011. doi: 10.1056/NEJMoa2005412
  • 32. Zhou F, Yu T, Du R, Fan G, Liu Y et al. Clinical course and risk factors for mortality of adult in-patients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020; 395 (10229): 1054-1062. doi: 10.1016/S0140-6736(20)30566-3
  • 33. Wu C, Chen X, Cai Y, Xia J, Zhou X et al. Risk Factors Associated with Acute Respiratory Distress Syndrome and Death in Patients with Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA International Medicine 2020; 13: e200994. doi: 10.1001/jamainternmed.2020.0994
  • 34. Henry BM, De Oliveira MHS, Benoit S, Plebani M, Lippi G. Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis. Clinical Chemistry and Laboratory Medicine 2020; 58 (7): 1021-1028. doi: 10.1515/cclm-2020-0369
  • 35. Lippi G, Plebani M. Laboratory abnormalities in patients with COVID-2019 infection. Clinical Chemistry and Laboratory Medicine 2020; 58 (7). doi: 10.1515/cclm-2020-0198
  • 36. Öztürk R, Taşova Y, Ayaz A. COVID-19: pathogenesis, genetic polymorphism, clinical features and laboratory findings. Turkish Journal of Medical Sciences 2020 21; 50(SI-1): 638-657. doi: 10.3906/sag-2005-287
  • 37. Williamson EJ, Walker AJ, Bhaskaran K, Bacon S, Bates C et al. Factors associated with COVID-19-related death using Open SAFELY. Nature 2020; 584 (7821): 430-436. doi: 10.1038/ s41586-020-2521-4
  • 38. Harrison SL, Fazio-Eynullayeva E, Lane DA, Underhill P, Lip GYH. Comorbidities associated with mortality in 31,461 adults with COVID-19 in the United States: A federated electronic medical record analysis. PLoS Medicine 2020; 17(9): e1003321. doi: 10.1371/journal.pmed.1003321
  • 39. Lowe KE, Zein J, Hatipoglu U, Attaway A. Association of Smoking and Cumulative Pack-Year Exposure With COVID-19 Outcomes in the Cleveland Clinic COVID-19 Registry. JAMA International Medicine 2021; 181 (5): 709-711. doi: 10.1001/ jamainternmed.2020.8360
  • 40. Tartof SY, Qian L, Hong V, Wei R, Nadjafi RF et al. Obesity and Mortality Among Patients Diagnosed With COVID-19: Results from an Integrated Health Care Organization. Annals of Internal Medicine 2020; 173 (10): 773-781. doi: 10.7326/ M20-3742
  • 41. Oran DP, Topol EJ. The Proportion of SARS-CoV-2 Infections That Are Asymptomatic: A Systematic Review. Annals of Internal Medicine 2021; 174 (5): 655-662. doi: 10.7326/M20- 6976
  • 42. Baggett TP, Keyes H, Sporn N, Gaeta JM. Prevalence of SARS-CoV-2 Infection in Residents of a Large Homeless Shelter in Boston. JAMA: The Journal of the American Medical Association 2020; 323 (21): 2191-2192. doi: 10.1001/ jama.2020.6887
  • 43. Kasper MR, Geibe JR, Sears CL, Riegodedios AJ, Luse T et al. An Outbreak of Covid-19 on an Aircraft Carrier. The New England Journal of Medicine 2020; 383 (25): 2417-2426. doi: 10.1056/NEJMoa2019375
  • 44. Crossette-Thambiah C, Nicolson P, Rajakaruna I, Langridge A, Sayar Z et al. The clinical course of COVID-19 in pregnant versus non-pregnant women requiring hospitalization: results from the multicentre UK CA-COVID-19 study. British Journal of Haematology 2021; 16. doi: 10.1111/bjh.17579
  • 45. Van de Veerdonk FL, Netea MG. Blocking IL-1 to prevent respiratory failure in COVID-19. Critical Care 2020; 24 (1): 445. doi: 10.1186/s13054-020-03166-0
  • 46. Beltrán-García J, Osca-Verdegal R, Pallardó FV, Ferreres J, Rodríguez M et al. Sepsis and Coronavirus Disease 2019: Common Features and Anti-Inflammatory Therapeutic Approaches. Critical Care Medicine 2020; 48 (12): 1841-1844 doi:10.1097/CCM.0000000000004625
  • 47. Zhou M, Zhang, X, Qu, J. Coronavirus disease 2019 (COVID-19): a clinical update. Frontiers of Medicine 2020; 14 (2): 126-135. doi: 10.1007/s11684-020-0767-8
  • 48. Severe Outcomes Among Patients with Coronavirus Disease 2019 (COVID-19) — United States, February 12–March 16, 2020. Morbidity and Mortality Weekly Report (MMWR). 2020; 69:343-346
  • 49. Arentz M, Yim E, Klaff L, Lokhandwala S, Riedo FX et al. Characteristics and Outcomes of 21 Critically Ill Patients With COVID-19 in Washington State. JAMA: The Journal of the American Medical Association 2020; 323 (16): 1612–1614. doi: 10.1001/jama.2020.4326
  • 50. Chen X, Peng F, Zhou X, Zhu J, Chen X et al. Predicting severe or critical symptoms in hospitalized patients with COVID-19 from Yichang, China. Aging 2021; 13 (2): 1608-1619. doi:10.18632/aging.202261
  • 51. Marini JJ, Gattinoni L. Management of COVID-19 Respiratory Distress. JAMA: The Journal of the American Medical Association 2020; 323 (22): 2329–2330. doi:10.1001/ jama.2020.6825
  • 52. Clinical management of COVID-19 patients: living guidance, January 25, 2021, https://app.magicapp.org/#/guideline/ j1WBYn, Severe Outcomes Among Patients with Coronavirus Disease 2019 (COVID-19) — United States, February 12– March 16, 2020. Morbidity and Mortality Weekly Report (MMWR) 2020; 69:343-346
  • 53. Cascella M, Rajnik M, Cuomo A, Dulebohn SC, Napoli RD. Features, Evaluation, and Treatment Coronavirus (COVID-19) Treasure Island, FL: StatPearls Publishing; [Mar;2020]. 2020. PMID: 32150360
  • 54. Nikhra V. Identifying patterns in COVID-19: Morbidity, recovery, and the aftermath. International Journal of Clinical Virology 2020; 4: 056-064. doi: 10.29328/journal.ijcv.1001016
  • 55. Cimolai N. The Complexity of Co-Infections in the Era of COVID-19. SN Comprehensive Clinical Medicine 2021; 1-13. https://doi.org/10.1007/s42399-021-00913-4
  • 56. Russell CD, Fairfield CJ, Drake TM, Turtle L, Seaton RA et al. Co-infections, secondary infections, and antimicrobial use in patients hospitalized with COVID-19 during the first pandemic wave from the ISARIC WHO CCP-UK study: a multicentre, prospective cohort study. Lancet Microbe 2021; 2(8): e354-e365. doi: 10.1016/S2666-5247(21)00090-2
  • 57. Langford BJ, So M, Raybardhan S, Leung V, Westwood D et al. Bacterial co-infection and secondary infection in patients with COVID-19: a living rapid review and meta-analysis. Clinical Microbiology and Infection 2020; 26 (12): 1622-1629. https:// doi.org/10.1016/j.cmi.2020.07.016
  • 58. Mao L, Jin H, Wang M, Hu Y, Chen S et al. Neurologic Manifestations of Hospitalized Patients Coronavirus Disease 2019 in Wuhan, China. JAMA Neurology. 2020; 77 (6): 683- 690. doi:10.1001/jamaneurol.2020.1127
  • 59. Di Carlo DT, Montemurro N, Petrella G, Siciliano G, Ceravolo R et al. Exploring the clinical association between neurological symptoms and COVID-19 pandemic outbreak: a systematic review of current literature. Journal of Neurology 2021; 268: 1561–1569. https://doi.org/10.1007/s00415-020-09978-y
  • 60. Acar T, Demirel EA, Afsar N, Akcalı A, Demiret GA et al. The COVID-19 from Neurological Overview. Turkish Journal of Neurology 2020; 26 (2): 58-108 doi: 10.4274/tnd.2020.73669
  • 61. Torales J, O’Higgins M, Castaldelli-Maia JM, Ventriglio A. The outbreak of COVID-19 coronavirus and its impact on global mental health. International Journal of Social Psychiatry 2020; 66 (4): 317-320. doi: 10.1177/0020764020915212
  • 62. Freeman EE, McMahon DE, Lipoff JB, Rosenbach M, Kovarik C et al. The spectrum of COVID-19-associated dermatologic manifestations: An international registry of 716 patients from 31 countries. Journal of the American Academy of Dermatology 2020; 83 (4): 1118-1129. doi: 10.1016/j.jaad.2020.06.1016
  • 63. Chilazi, M, Duffy, E.Y, Thakkar A, Michos ED COVID and Cardiovascular Disease: What We Know in 2021. Current Atherosclerosis Reports 2021; 23: 37. https://doi.org/10.1007/ s11883-021-00935-2
  • 64. El Rhalete A, Rhazi I, Bensaid A, Zaid I, Bkiyer H et al. Cardiovascular injuries during COVID-19 infection: A PROCESS-compliant case series from Eastern Morocco. Annals of Medicine and Surgery 2021; 65: 102309. doi: 10.1016/j. amsu.2021.102309
  • 65. Migliaccio MG, Di Mauro M, Ricciolino R, Spiniello G, Carfora V et al. Renal Involvement in COVID-19: A Review of the Literature. Infection and Drug Resistance 2021; 14: 895- 903. doi: https://doi.org/10.2147/IDR.S288869
  • 66. Garg MK, Gopalakrishnan M, Yadav P, Misra S. Endocrine Involvement in COVID-19: Mechanisms, Clinical Features, and Implications for Care. Indian Journal of Endocrinology Metabolism 2020; 24 (5): 381-386. doi: 10.4103/ijem. IJEM_440_20
  • 67. Vespa E, Pugliese N, Colapietro F, Aghemo A. Stay (GI) Healthy: COVID-19 and Gastrointestinal Manifestations. Techniques and Innovations in Gastrointestinal Endoscopy 2021; 179-189. https://doi.org/10.1016/j.tige.2021.01.006
  • 68. Nasiri N, Sharifi H, Bazrafshan A, Noori A, Karamouzian M et al. Ocular Manifestations of COVID-19: A Systematic Review and Meta-analysis. Journal of Ophthalmic and Vision Research 2021; 16 (1): 103-112. doi: 10.18502/jovr. v16i1.8256
APA Çelik İ, Ozturk R (2021). From asymptomatic to critical illness: decoding various clinical stages of COVID-19. , 3284 - 3300. 10.3906/sag-2107-137
Chicago Çelik İlhami,Ozturk Recep From asymptomatic to critical illness: decoding various clinical stages of COVID-19. (2021): 3284 - 3300. 10.3906/sag-2107-137
MLA Çelik İlhami,Ozturk Recep From asymptomatic to critical illness: decoding various clinical stages of COVID-19. , 2021, ss.3284 - 3300. 10.3906/sag-2107-137
AMA Çelik İ,Ozturk R From asymptomatic to critical illness: decoding various clinical stages of COVID-19. . 2021; 3284 - 3300. 10.3906/sag-2107-137
Vancouver Çelik İ,Ozturk R From asymptomatic to critical illness: decoding various clinical stages of COVID-19. . 2021; 3284 - 3300. 10.3906/sag-2107-137
IEEE Çelik İ,Ozturk R "From asymptomatic to critical illness: decoding various clinical stages of COVID-19." , ss.3284 - 3300, 2021. 10.3906/sag-2107-137
ISNAD Çelik, İlhami - Ozturk, Recep. "From asymptomatic to critical illness: decoding various clinical stages of COVID-19". (2021), 3284-3300. https://doi.org/10.3906/sag-2107-137
APA Çelik İ, Ozturk R (2021). From asymptomatic to critical illness: decoding various clinical stages of COVID-19. Turkish Journal of Medical Sciences, 51(Özel Sayı 1), 3284 - 3300. 10.3906/sag-2107-137
Chicago Çelik İlhami,Ozturk Recep From asymptomatic to critical illness: decoding various clinical stages of COVID-19. Turkish Journal of Medical Sciences 51, no.Özel Sayı 1 (2021): 3284 - 3300. 10.3906/sag-2107-137
MLA Çelik İlhami,Ozturk Recep From asymptomatic to critical illness: decoding various clinical stages of COVID-19. Turkish Journal of Medical Sciences, vol.51, no.Özel Sayı 1, 2021, ss.3284 - 3300. 10.3906/sag-2107-137
AMA Çelik İ,Ozturk R From asymptomatic to critical illness: decoding various clinical stages of COVID-19. Turkish Journal of Medical Sciences. 2021; 51(Özel Sayı 1): 3284 - 3300. 10.3906/sag-2107-137
Vancouver Çelik İ,Ozturk R From asymptomatic to critical illness: decoding various clinical stages of COVID-19. Turkish Journal of Medical Sciences. 2021; 51(Özel Sayı 1): 3284 - 3300. 10.3906/sag-2107-137
IEEE Çelik İ,Ozturk R "From asymptomatic to critical illness: decoding various clinical stages of COVID-19." Turkish Journal of Medical Sciences, 51, ss.3284 - 3300, 2021. 10.3906/sag-2107-137
ISNAD Çelik, İlhami - Ozturk, Recep. "From asymptomatic to critical illness: decoding various clinical stages of COVID-19". Turkish Journal of Medical Sciences 51/Özel Sayı 1 (2021), 3284-3300. https://doi.org/10.3906/sag-2107-137