What do we know about post-COVID syndrome?

The study of post-COVID syndrome (PCS) is relevant. The aim of the review is to study and summarize data on the features of PCS from the literature over the past 3 years. Manifestations of PCS have many variants, different duration and severity. Patients with PCS suffer from fatigue, mood swings and persistent respiratory symptoms, cognitive and psycho-emotional disturbances. Frequent neuropsychiatric manifestations of PCS are speech disorders, headache, dysgeusia, hypo- or anosmia. Severe PCS can provoke the development of acute cerebrovascular accident, Guillain-Barré syndrome, encephalitis or encephalopathy. The researchers found that the symptoms of PCS can range from persistent cough, dyspnea and postural orthostatic tachycardia to renal failure, myocarditis, and pulmonary fibrosis. The persistence of manifestations of PCS can be different. Often, PCS is completely stopped, but in some patients it has persistent manifestations. The researchers found that tachycardia and cardialgia disappeared in 8 months after suffering COVID-19. Fatigue and dyspnea persisted up to 1 year after experiencing COVID-19. The number of chronic somatic pathologies is associated with the incidence of increased fatigue and dyspnea after suffering from COVID-19. Thus, it was found that the manifestations of PCS have a multisystem character and long-term persistence. Most often there are feelings of fatigue, a decrease in tolerance to physical activity, cognitive and psycho-emotional disorders after suffering from COVID-19.

1. Bakina AA, Pavlenko VI, Khripunova ОА. Osobennosti rentgenologicheskoi kartiny COVID-19 – pnevmonii [Features of X-ray for pneumonia at Covid-19]. XXXII Natsional’nyi kongress po boleznyam organov dykhaniya : sbornik trudov [XXXII National Congress on respiratory diseases. Collection of works of Congress. Chucalin AG (ed.)]. Moscow: Design press; 2022. P. 77. (In Russ.)

2. Kulik EG, Pavlenko VI, Naryshkina SV. Pokazateli kachestva zhizni u bol’nykh KhOBL, perenesshikh novuyu koronavirusnuyu infektsiyu [Indicators of the quality of life in patients with COPD and COVID-19]. XXXII Natsional’nyi kongress po boleznyam organov dykhaniya : sbornik trudov [XXXII National Congress on respiratory diseases. Collection of works of Congress. Chucalin AG (ed.)]. Moscow: Design press; 2022. P. 130. (In Russ.).

3. Kulik E.G., Pavlenko V.I., Naryshkina S.V. Sravnitel’nyi analiz kliniko-laboratornykh pokazatelei u bol’nykh KhOBL v zavisimosti ot nalichiya obostreniya ili novoi koronavirusnoi infektsii [Comparative analysis of clinical and laboratory features in patients with chronic obstructive pulmonary disease depending on the presence of an exacerbation or a novel coronavirus infection]. Byulleten’ fiziologii i patologii dykhaniya . – Bulletin Physiology and Pathology of Respiration. 2022;85:26–31 (In Russ.). https://doi.org/10.36604/19985029-2022-85-26-31.

4. Pavlenko V.I., Kulik E.G., Naryshkina S.V. Khronicheskaya obstruktivnaya bolezn’ legkikh kak komorbidnoe sostoyanie pri COVID-19 [Chronic obstructive pulmonary disease as a comorbid state in Covid-19]. Amurskii meditsinskii zhurnal. – Amur Medical Journal. 2021;1(31):11–17. (In Russ.). https://doi.org/10.24412/2311-5068-2021-1-11-17.

5. Ayoubkhani D, Khunti K, Nafilyan V, Maddox T, Humberstone B, Diamond I, Banerjee A. Post-COVID syndrome in individuals admitted to hospital with covid-19: retrospective cohort study. BMJ. 2021;372:n693. https://doi.org/10.1136/bmj.n693.

6. Ceban F, Ling S, Lui LMW, Lee Y, Gill H, Teopiz KM, et al. Fatigue and cognitive impairment in Post-COVID-19 Syndrome: A systematic review and meta-analysis. Brain Behav Immun. 2022;101:93-135. https:// doi.org/10.1016/j.bbi.2021.12.020.

7. Chan JF, Yuan S, Kok KH, To KK, Chu H, Yang J, 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;395:514-523. https://doi.org/10.1016/S0140-6736(20)30154-9.

8. Changeux JP, Amoura Z, Rey FA, Miyara M. A nicotinic hypothesis for COVID-19 with preventive and therapeutic implications. C R Biol. 2020;343(1):1–7. https://doi.org/10.5802/crbiol.8. PMID: 32720486.

9. Chudzik M, Babicki M, Kapusta J, Kałuzińska-Kołat Ż, Kołat D, Jankowski P., Mastalerz-Migas A. Long-COVID clinical features and risk factors: a retrospective analysis of patients from the STOP-COVID registry of the PoLoCOV study. Viruses. 2022;14(8):1755. https://doi.org/10.3390/v14081755.

10. Chung TH, Azar A. Autonomic nerve involvement in post-acute sequelae of SARS-CoV-2 syndrome (PASC). J Clin Med. 2022;12(1):73. https://doi.org/10.3390/jcm12010073.

11. Coronavirus disease (COVID-19) – World Health Organization. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019. [Accessed: June 27, 2021]

12. Davis HE, Assaf G.S, McCorkell L, Wei H, Low RJ, Re’em Y., et al. Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. E Clinical Medicine. 2021;38:101019. https:// doi.org/10.1016/j.eclinm.2021.101019.

13. Feikin DR, Higdon MM, Abu-Raddad LJ, Andrews N, Araos R, Goldberg Y., et al. Duration of effectiveness of vaccines against SARS-CoV-2 infection and COVID-19 disease: results of a systematic review and meta-regression. Lancet. 2022;399:924-44. https://doi.org/10.1016/S0140-6736(22)00152-0.

14. Fernández-de-Las-Peñas C, Gómez-Mayordomo V, Cuadrado ML, Palacios-Ceña D, Florencio LL, Guerrero AL., et al. The presence of headache at onset in SARS-CoV-2 infection is associated with longterm post-COVID headache and fatigue: A case-control study. Cephalalgia. 2021:41(13):1332-41. https://doi.org/10.1177/03331024211020404.

15. Fernández-de-Las-Peñas C, Guijarro C, Torres-Macho J, Velasco-Arribas M, Plaza-Canteli S, Hernández-Barrera V., et al. Diabetes and the risk of long-term post-COVID symptoms. Diabetes. 2021; 70(12):2917-21. https://doi.org/10.2337/db21-0329.

16. Fernández-de-Las-Peñas C., Rodríguez-Jiménez J., Cancela-Cilleruelo I., Guerrero-Peral A., Martín-Guerrero J.D., García-Azorín D., et al. Post-COVID-19 symptoms 2 years after SARS-CoV-2 infection among hospitalized vs nonhospitalized patients. JAMA Netw Open. 2022;5(11):e2242106. https://doi.org/10.1001/jamanetworkopen.2022.42106.

17. Fernández-de-Las-Peñas C, Ryan-Murua P, Rodríguez-Jiménez J, Palacios-Ceña M, Arendt-Nielsen L, Torres-Macho J. Serological biomarkers at hospital admission are not related to long-term post-COVID fatigue and dyspnea in COVID-19 survivors. Respiration. 2022;101(7):658-665. https://doi.org/10.1159/000524042.

18. Goërtz YMJ, Van Herck M, Delbressine JM, Vaes AW, Meys R, Machado FVC, Houben-Wilke S, Burtin C, Posthuma R, Franssen FME, van Loon N, Hajian B, Spies Y, Vijlbrief H, van ‘t Hul AJ, Janssen DJA, Spruit MA. Persistent symptoms 3 months after a SARS-CoV-2 infection: the post-COVID-19 syndrome? ERJ Open Res. 2020 Oct 26;6(4):00542-2020. https://doi.org/10.1183/23120541.00542-2020. PMID: 33257910; PMCID: PMC7491255.

19. Guntur VP, Nemkov T, de Boer E, Mohning MP, Baraghoshi D, Cendali FI., et al. Signatures of mitochondrial dysfunction and impaired fatty acid metabolism in plasma of patients with post-acute sequelae of COVID-19 (PASC). Metabolites. 2022;12(11):1026. https://doi.org/10.3390/metabo12111026.

20. Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H., et al. Washington State 2019-nCoV Case Investigation Team. First Case of 2019 Novel Coronavirus in the United States. N Engl J Med. 2020;382;10:929-936. https://doi.org/10.1056/NEJMoa2001191.

21. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y., et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395:497-506. https://doi.org/10.1016/S0140-6736(20)30183-5.

22. Kamal M, Abo Omirah M, Hussein A, Saeed H. Assessment and characterisation of post-COVID-19 manifestations. Int J Clin Pract. 2021;75:e13746. https://doi.org/10.1111/ijcp.13746.

23. Lee JH, Yim JJ, Park J. Pulmonary function and chest computed tomography abnormalities 6-12 months after recovery from COVID-19: a systematic review and meta-analysis. Respir Res. 2022;23(1):233. Https://doi.org/10.1186/s12931-022-02163-x.

24. Liang L, Yang B, Jiang N, Fu W, He X, Zhou Y., et al. Three-month Follow-up Study of Survivors of Coronavirus Disease 2019 after Discharge. J Korean Med Sci. 2020;35(47):e418. https://doi.org/10.3346/jkms.2020.35.e418.

25. Loosen SH, Jensen BO, Tanislav C, Luedde T, Roderburg C, Kostev K. Obesity and lipid metabolism disorders determine the risk for development of long COVID syndrome: a cross-sectional study from 50,402 COVID-19 patients. Infection. 2022;50(5):1165-1170. https://doi.org/10.1007/s15010-022-01784-0.

26. Mizrahi B, Sudry T, Flaks-Manov N, Yehezkelli Y, Kalkstein N, Akiva P., et al. Long COVID outcomes at one year after mild SARS-CoV-2 infection: nationwide cohort study. BMJ. 2023;380:e072529. https://doi.org/10.1136/bmj-2022-072529.

27. Nalbandian A, Sehgal K, Gupta A, Madhavan MV, McGroder C, Stevens JS., et al. Post-acute COVID-19 syndrome. Nat Med. 2021;27;4:601-615. https://doi.org/10.1038/s41591-021-01283-z.

28. Nateghi S, Hesari E, Mansouri F, Akrami M, Pourian M, Khosravani A., et al. Evaluation of blood biochemistry and cardiopulmonary status of hospitalized COVID-19 patients in 3 months post discharged follow up survey. Clin Med Insights Circ Respir Pulm Med. 2022;16:11795484221119332. https://doi.org/10.1177/11795484221119332.

29. Notarte KI, de Oliveira MHS., Peligro PJ, Velasco JV, Macaranas I, Ver AT., et al. Age, sex and previous comorbidities as risk factors not associated with SARS-CoV-2 infection for long COVID-19: A Systematic Review and Meta-Analysis. J Clin Med. 2022;11(24):7314. https://doi.org/10.3390/jcm11247314.

30. Peghin M, Palese A, Venturini M, De Martino M, Gerussi V, Graziano E., et al. Post-COVID-19 symptoms 6 months after acute infection among hospitalized and non-hospitalized patients. Clin Microbiol Infect. 2021;27(10):1507-1513. https://doi.org/10.1016/j.cmi.2021.05.033.

31. Phan LT, Nguyen TV, Luong QC, Nguyen TV, Nguyen HT, Le HQ., et al. Importation and Humanto-Human Transmission of a Novel Coronavirus in Vietnam. N Engl J Med. 2020;382;9:872-874. https://doi.org/10.1056/NEJMc2001272.

32. Rothe C, Schunk M, Sothmann P, Bretzel G, Froeschl G, Wallrauch C., et al. Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany. N Engl J Med. 2020;382;10:970–971. https://doi.org/10.1056/NEJMc2001468.

33. Rubin R. As their numbers grow, COVID-19 «Long haulers» stump experts. JAMA. 2020;324;14:1381-1383. https://doi.org/10.1001/jama.2020.17709.

34. Shang L, Wang L, Zhou F, Li J, Liu Y, Yang S. Long-term effects of obesity on COVID-19 patients discharged from hospital. Immun Inflamm Dis. 2021;9(4);1678-1685. https://doi.org/10.1002/iid3.522.

35. Siegelman JN. Reflections of a COVID-19 long hauler. JAMA. 2020;324;20:2031-2032. https://doi.org/10.1001/jama.2020.22130.

36. Stavem K, Ghanima W, Olsen MK, Gilboe HM, Einvik G. Persistent symptoms 1.5-6 months after COVID-19 in non-hospitalised subjects: a population-based cohort study. Thorax. 2021;76(4):405-407. https://doi.org/10.1136/thoraxjnl-2020-216377.

37. Subramanian A, Nirantharakumar K, Hughes S, Myles P, Williams T, Gokhale KM., et al. Symptoms and risk factors for long COVID in non-hospitalized adults. Nat Med. 2022;28(8):1706-14. https://doi.org/10.1038/s41591-022-01909-w.

38. Talic S, Shah S, Wild H, Gasevic D, Maharaj A, Ademi Z., et al. Effectiveness of public health measures in reducing the incidence of covid-19, SARS-CoV-2 transmission, and covid-19 mortality: systematic review and meta-analysis. BMJ. 2021;375:e068302. https://doi.org/10.1136/bmj-2021-068302.

39. Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18;4:844-847. https://doi.org/10.1111/jth.14768.

40. World Health Organization. Coronavirus disease (COVID-19) outbreak. Available from: https://www.who.int.

41. Wulf Hanson S, Abbafati C, Aerts JG, Al-Aly Z, Ashbaugh C, Ballouz T., et al. 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):1604-1615. https://doi.org/10.1001/jama.2022.18931.

42. Xu E, Xie Y, Al-Aly Z. Long-term neurologic outcomes of COVID-19. Nat Med. 2022;28(11):2406-2415. Https://doi.org/10.1038/s41591-022-02001-z.

43. Yang T, Yan MZ, LiX, Lau EHY. Sequelae of COVID-19 among previously hospitalized patients up to 1 year after discharge: a systematic review and meta-analysis. Infection. 2022;50(5):1067-1109. https://doi.org/10.1007/s15010-022-01862-3.

44. Yazji B, Voduc N, Mulpuru S, Cowan J. Pulmonary sequelae of SARS-CoV-2 infection and factors associated with persistent abnormal lung function at six months after infection: Prospective cohort study. PLoS One. 2022;17(11):e0277624. https://doi.org/10.1371/journal.pone.0277624.