Post-COVID syndrome: accumulated knowledge and unresolved questions
https://doi.org/10.22448/AMJ.2025.1.64-72
Abstract
In 2019, a novel coronavirus infection (COVID-19) emerged globally and was declared a pandemic by the World Health Organization. Early studies of COVID-19 revealed that even after resolution of acute symptoms, patients continued to experience a wide range of nonspecific complaints that significantly impaired quality of life for prolonged periods. This condition became known as “postCOVID syndrome” (PCS).
Objective of the review is to analyze and summarize data from Russian and international studies focusing on the pathogenetic mechanisms and clinical manifestations of PCS. ,
Main findings. Initial reports of persistent nonspecific symptoms following recovery from COVID-19 appeared in early 2020. Subsequently, healthcare providers increasingly noted that nonspecific complaints – such as unexplained general weakness, fatigue, pain syndromes, and dyspnea – were becoming common reasons for patient visits. Initially thought to primarily affect older adults, further research indicated that children and adolescents are similarly susceptible to developing PCS. A comprehensive investigation into the pathogenesis of PCS has revealed multiple underlying mechanisms contributing to its development. Conclusion. Understanding the phenomenon of PCS requires acknowledging the complexity of its pathogenetic mechanisms and the multisystem nature of its manifestations. Researchers still face numerous unresolved questions in establishing a unified, comprehensive understanding of the disease and identifying effective therapeutic strategies for patients with PCS.
About the Authors
A. A. Bakina
Amur State Medical Academy Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
Anastasia A. Bakina
Blagoveshchensk
V. I. Pavlenko
Amur State Medical Academy Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
Valentina I. Pavlenko
Blagoveshchensk
E. G. Kulik
Amur State Medical Academy Ministry of Health of the Russian Federation
Russian Federation
Russian Federation
Ekaterina G. Kulik
Blagoveshchensk
References
1. Chan J.F., Yuan S., Kok K.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): 514–523. DOI: https://doi.org/10.1016/S0140-6736(20)30154-9
2. Phan L.T., Nguyen T.V., Luong Q.C., et al. Importation and Human-to-Human Transmission of a Novel Coronavirus in Vietnam. New England Journal of Medicine. 2020; 382 (9): 872–874. DOI: https://doi.org/10.1056/NEJMc2001272
3. Huang C., Wang Y., Li X., et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020; 395 (10223): 497–506. DOI: https://doi.org/10.1016/S0140-6736(20)30183-5
4. Tang N., Li D., Wang X., Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. Journal of Thrombosis and Haemostasis. 2020; 18 (4): 844–847. DOI: https://doi.org/10.1111/jth.14768
5. Kulik E.G., Pavlenko V.I., Galoyan A.V. Interrelation of parameters of acid-base state and electrolyte composition of blood with indicators of systemic inflammation in patients with chronic obstructive pulmonary disease and COVID-19. Therapy. 2022; 8 (S7-59): 126–127. (In Russ.)
6. Kulik E.G., Pavlenko V.I., Naryshkina S.V. 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. Bulletin Physiology and Pathology of Respiration. 2022; 85: 26–31. DOI: https://doi.org/10.36604/1998-5029-2022-85-26-31
7. Davis H.E., Assaf G.S., McCorkell L., et al. Characterizing long COVID in an international cohort: 7 months of symptoms and their impact. eClinicalMedicine. 2021; 38: 101019. DOI: https://doi.org/10.1016/j.eclinm.2021.101019
8. Fernandez-de-Las-Penas C., Rodriguez-Jimenez J., Cancela-Cilleruelo I., et al. Post-COVID-19 symptoms 2 years after SARS-CoV-2 infection among hospitalized vs nonhospitalized patients. JAMA Network Open. 2022; 11 (5): e2242106. DOI: https://doi. org/10.1001/jamanetworkopen.2022.42106
9. Goërtz Y.M.J., Van Herck M., Delbressine J.M., et al. Persistent symptoms 3 months after a SARS-CoV-2 infection: the post-COVID-19 syndrome? European Respiratory Journal Open Research. 2020; 6 (4): 00542–2020. DOI: https://doi.org/10.1183/23120541.00542-2020
10. Tanerova NG. Analysis of post-COVID syndrome course based on patient questionnaire data. Journal of Young Scientists. 2022; 11 (2): 58–60.
11. Wise J. Long covid: WHO calls on countries to offer patients more rehabilitation. British Medical Journal. 2021; 372: n405. DOI: https://doi.org/10.1136/bmj.n405
12. Rogers J.P., Chesney E., Oliver D., et al. Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic. Lancet Psychiatry. 2020; 7 (7): 611–627. DOI: https://doi.org/10.1016/S2215-0366(20)30203-0
13. de Melo G.D., Lazarini F., Levallois S., et al. COVID-19-related anosmia is associated with viral persistence and inflammation in human olfactory epithelium and brain infection in hamsters. Science Translational Medicine. 2021; 13 (596): eabf8396. DOI: https://doi.org/10.1126/scitranslmed.abf8396
14. Nateghi S., Hesari E., Mansouri F., et al. Evaluation of blood biochemistry and cardiopulmonary status of hospitalized COVID-19 patients in 3 months post discharged follow up survey. Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine. 2022; 16: 11795484221119332. DOI: https://doi.org/10.1177/11795484221119332
15. Zuo W., He D., Liang C., et al. The persistence of SARSCoV-2 in tissues and its association with long COVID symptoms: a cross-sectional cohort study in China. Lancet Infectious Diseases. 2024; 24 (8): 845–855. DOI: https://doi.org/10.1016/S1473-3099(24)00171-3
16. Chichanovskaya L.V., Vinogradova A.A., Raud A.K. and others. Autonomic dysfunction in patients with diagnosed postcovoid syndrome. Tver Medical Journal. 2023; 1: 82–85.
17. Kamal M., Abo Omirah M., Hussein A., Saeed H. Assessment and characterisation of post-COVID-19 manifestations. International Journal of Clinical Practice. 2021; 75 (3): e13746. DOI: https://doi.org/10.1111/ijcp.13746
18. Bakhtina I.S., Kalinina S.A., Garderobova L.V., et al. Chronic pain syndrome in patients with post-covid syndrome: nursing rehabilitation care. Physical and Rehabilitation Medicine. 2023; 5 (1): 9–18. DOI: https://doi.org/10.26211/2658-4522-2023-5-1-9-18
19. Xie Y., Bowe B., Al-Aly Z. Burdens of post-acute sequelae of COVID-19 by severity of acute infection, demographics and health status. Nature Communications. 2021; 12(1): 6571. DOI: https://doi.org/10.1038/s41467-021-26513-3
20. Stephenson T., Pinto Pereira S.M., Nugawela M.D., et al. A 24-month National Cohort Study examining long-term effects of COVID-19 in children and young people. Communications Medicine. 2024; 4 (1): 255. DOI: https://doi.org/10.1038/s43856-024-00657-x
21. Behnood S., Newlands F., O'Mahoney L., et al. Persistent symptoms are associated with long term effects of COVID-19 among children and young people: Results from a systematic review and meta-analysis of controlled studies. PLoS One. 2023; 18 (12): e0293600. DOI: https://doi.org/10.1371/journal.pone.0293600
22. Pazukhina E., Rumyantsev M., Baimukhambetova D., et al. Event rates and incidence of postCOVID-19 condition in hospitalised SARS-CoV-2 positive children and young people and controls across different pandemic waves: exposure-stratified prospective cohort study in Moscow (StopCOVID). BMC Medice. 2024; 22 (1): 48. DOI: https://doi.org/10.1186/s12916-023-03221-x
23. Pinto Pereira S.M., Nugawela M.D., Stephenson T., et al.; CLoCk Consortium; Shafran R. Post-Covid-19 condition (Long Covid) in children and young people 12 months after infection or reinfection with the Omicron variant: a prospective observational study. Scientific Reports. 2024; 14 (1): 9957. DOI: https://doi.org/10.1038/s41598-024-60372-4
24. Stein S.R., Ramelli S.C., Grazioli A., et al. SARS-CoV-2 infection and persistence in the human body and brain at autopsy. Nature. 2022; 612 (7941): 758–763. DOI: https://doi.org/10.1038/s41586-022-05542-y
25. Lu S., Peluso M.J., Glidden D.V., et al. Early biological markers of post-acute sequelae of SARS-CoV-2 infection. Nature Communications. 2024; 15 (1): 7466. DOI: https://doi.org/10.1038/s41467-024-51893-7
26. Peluso M.J., Deeks S.G., Mustapic M., et al. SARSCoV-2 and mitochondrial proteins in neural-derived exosomes of COVID-19. Annals of Neurology. 2022; 91 (6): 772–781. DOI: https://doi.org/10.1002/ana.26350
27. Queiroz M.A.F., Neves P.F.M.D., Lima S.S., et al. Cytokine profiles associated with acute COVID-19 and long COVID-19 syndrome. Frontiers in Cellular and Infection Microbiology. 2022; 12: 922422. DOI: https://doi.org/10.3389/fcimb.2022.922422
28. Schultheiß C., Willscher E., Paschold L., et al. The IL-1β, IL-6, and TNF cytokine triad is associated with post-acute sequelae of COVID-19. Cell Reports Medicine. 2022; 3 (6): 100663. DOI: https://doi.org/10.1016/j.xcrm.2022.100663
29. Schultheiß C., Willscher E., Paschold L., et al. Liquid biomarkers of macrophage dysregulation and circulating spike protein illustrate the biological heterogeneity in patients with post-acute sequelae of COVID-19. Journal of Medical Virology. 2023; 95 (1): e28364. DOI: https://doi.org/10.1002/jmv.28364
30. GBD 2021 Demographics Collaborators. Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021. Lancet. 2024; 403 (10440): 1989–2056. DOI: https://doi.org/10.1016/S0140-6736(24)00476-8
31. Fleischer M., Szepanowski F., Mausberg A.K., et al. Cytokines (IL1β, IL6, TNFα) and serum cortisol levels may not constitute reliable biomarkers to identify individuals with post-acute sequelae of COVID-19. Therapeutic Advances in Neurological Disorders. 2024; 17: 17562864241229567. DOI: https://doi.org/10.1177/17562864241229567
32. Li H., Zhao X., Wang Y., et al. Damaged lung gas exchange function of discharged COVID-19 patients detected by hyperpolarized 129Xe MRI. Science Advances. 2021; 7 (1): eabc8180. DOI: https://doi.org/10.1126/sciadv.abc8180
33. Matheson A.M., McIntosh M.J., Kooner H.K., et al. Longitudinal follow-up of postacute COVID-19 syndrome: DLCO, quality-of-life and MRI pulmonary gas-exchange abnormalities. Thorax. 2023; 78 (4): 418–421. DOI: https://doi.org/10.1136/thorax-20.
Review
For citations:
Bakina A.A., Pavlenko V.I., Kulik E.G. Post-COVID syndrome: accumulated knowledge and unresolved questions. Amur Medical Journal. 2025;13(1):64-72. (In Russ.) https://doi.org/10.22448/AMJ.2025.1.64-72
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