Peculiarities of the clinical course and risk factors of long-lasting post-COVID syndrome in patients with shortness of breath
Abstract. Post-COVID syndrome (PCS) has a high prevalence rate (from 4 to 80%) and is represented by more than 200 symptoms, including shortness of breath. At the same time, the structure of risk factors, pathogenetic mechanisms of prolonged PCS have not been sufficiently studied. Study of these issues is a promising direction in therapy, which can help in preventing the occurrence of PCS and ensuring its effective treatment.Masalkina O.V., Polyanskaya E.A., Koziolova N.A., Chernyavina A.I.
The aim: to determine the prevalence, peculiarities of clinical course and risk factors for long-lasting PCS development in patients with dyspnea.
Material and methods. A screening cross-sectional clinical study was performed. 887 patients applied to outpatient clinic due to shortness of breath after a new coronavirus infection (NCVI) from March 2020 to August 2023. The study included 205 individuals, who were divided into 3 groups: 1st – 62 patients with PCS > 3 months; 2nd – 52 patients with PCS < 3 months; 3rd – 91 patients without PCS.
Results. The average duration of the period after a new coronavirus infection in studied patients was 7.3 [3.2; 12.8] months. Patients in the group with PCS ≥ 3 months had statistically significantly higher mean values for NCVI with hospitalization, NCVI with pneumonia, NCVI accompanied by weakness, NCVI with general feeling of being unwell, NCVI with cognitive impairment, NCVI with dyspnea, NCVI with significant lung damage. An increase of D-dimer level increased the odds ratio (OR) of developing PCS lasting > 3 months by 4 times, and an increase of N-terminal fragment of the B-type brain natriuretic peptide (NT-proBNP) – by 9.4 times comparatively to the group of patients without PCS. An increase in the concentration of tumor necrosis factor-alpha increased the OR of developing PCS lasting < 3 months by 8 times comparatively to the group of patients without PCS.
Conclusion. The severity of NCVI clinical course with hospitalization, pneumonia, appearance of pulmonary fibrosis affects the formation of long-lasting PCS. Risk factors for the development of long-lasting PCS include increased levels of D-dimer, NT-proBNP, increased body mass index, left ventricular myocardial hypertrophy.
Keywords
shortness of breath
long-lasting post-COVID syndrome
D-dimer
N-terminal fragment of brain B-type natriuretic peptide
References
1. World Health Organization. Post COVID-19 condition (Long COVID). URL: https://www.who.int/europe/news-room/fact-sheets/item/post-covid-19-condition (date of access – 11.03.2025).
2. Appel K.S., Nürnberger C., Bahmer T. et al.; NAPKON Study Group. Definition of the Post-COVID syndrome using a symptom-based Post-COVID score in a prospective, multi-center, cross-sectoral cohort of the German National Pandemic Cohort Network (NAPKON). Infection. 2024; 52(5): 1813–29.
https://doi.org/10.1007/s15010-024-02226-9. PMID: 38587752. PMCID: PMC11499320.
3. Peter R.S., Nieters A., Kräusslich H.-G. et al.; EPILOC Phase 1 Study Group. Post-acute sequelae of COVID-19 six to 12 months after infection: Population based study. BMJ. 2022; 379: e071050.
https://doi.org/10.1136/bmj-2022-071050. PMID: 36229057. PMCID: PMC9557001.
4. COVID-19 rapid guideline: Managing the long-term effects of COVID-19. London: National Institute for Health and Care Excellence (NICE). 2024. PMID: 33555768. ISBN-13: 978-1-4731-3943-5.
5. A multidisciplinary NHS COVID-19 service to manage post-COVID-19 syndrome in the community. J Prim Care Community Health. 2021; 12: 21501327211010994.
https://doi.org/10.1177/21501327211010994. PMID: 33880955. PMCID: PMC8064663.
6. Razak R.S.A., Ismail A., Aziz A.F.A. et al. Post-COVID syndrome prevalence: A systematic review and meta-analysis. BMC Public Health. 2024; 24(1): 1785.
https://doi.org/10.1186/s12889-024-19264-5. PMID: 38965510. PMCID: PMC11223303.
7. Позднякова Д.Д., Бахарева Т.А., Баранова И.А. с соавт. Реабилитационная программа постковидного синдрома с применением оксида азота и молекулярного водорода. Терапевтический архив. 2024; 96(3): 260–265. (Pozdnyakova D.D., Bakhareva T.A., Baranova I.A. et al. Rehabilitation program of post-COVID-19 syndrome with the use of nitric oxide and molecular hydrogen. Terapevticheskiy arkhiv = Therapeutic Archive. 2024; 96(3): 260–265 (In Russ.)).
https://doi.org/10.26442/00403660.2024.03.202639. EDN: NBNFLY.
8. Xie Y., Choi T., Al-Aly Z. Postacute sequelae of SARS-CoV-2 infection in the pre-delta, delta, and omicron eras. N Engl J Med. 2024; 391(6): 515–25.
https://doi.org/10.1056/nejmoa2403211. PMID: 39018527. PMCID: PMC11687648.
9. Fernandez-de-Las-Penas C., Notarte K.I., Macasaet R. et al. Persistence of post-COVID symptoms in the general population two years after SARS-CoV-2 infection: A systematic review and meta-analysis. J Infect. 2024; 88(2): 77–88.
https://doi.org/10.1016/j.jinf.2023.12.004. PMID: 38101521.
10. Mahler D.A., Wells C.K. Evaluation of clinical methods for rating dyspnea. Chest. 1988; 93(3): 580–86.
https://doi.org/10.1378/chest.93.3.580. PMID: 3342669.
11. Fernandez-de-Las-Penas C., Palacios-Ceña D., Gomez-Mayordomo V. et al. Prevalence of post-COVID-19 symptoms in hospitalized and non-hospitalized COVID-19 survivors: A systematic review and meta-analysis. Eur J Intern Med. 2021; 92: 55–70.
https://doi.org/10.1016/j.ejim.2021.06.009. PMID: 34167876. PMCID: PMC8206636.
12. Rocha R.P.S., Andrade A.C.S., Melanda F.N., Muraro A.P. Post-COVID-19 syndrome among hospitalized COVID-19 patients: A cohort study assessing patients 6 and 12 months after hospital discharge. Cad Saúde Pública. 2024; 40(2): e00027423.
https://doi.org/10.1590/0102-311XPT027423. PMID: 38381868. PMCID: PMC10877698.
13. Abdel-Gawad M., Zaghloul M.S., Abd-Elsalam S. et al. Post-COVID-19 syndrome clinical manifestations: A systematic review. Antiinflamm Antiallergy Agents Med Chem. 2022; 21(2): 115–20.
https://doi.org/10.2174/1871523021666220328115818. PMID: 35346011.
14. Yong S.J., Liu S. Proposed subtypes of post-COVID-19 syndrome (or long-COVID) and their respective potential therapies. Rev Med Virol. 2022; 32(4): e2315.
https://doi.org/10.1002/rmv.2315. PMID: 34888989.
15. Фролова Е.С., Веселовский П.П., Чумакова Г.А. с соавт. Особенности течения COVID-19 и постковидного периода у пациентов с ожирением. CardioСоматика. 2024; 15(4): 344–353. (Frolova E.S., Veselovsky P.P., Chumakova G.A. et al. COVID-19 and post-disease features in patients with obesity. CardioSomatika = CardioSomatics. 2024; 15(4): 344–353 (In Russ.)).
https://doi.org/10.17816/CS626503. EDN: BCUJCL.
16. Simonnet A., Chetboun M., Poissy J. et al.; LICORN and the Lille COVID-19 and Obesity study group. High prevalence of obesity in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) requiring invasive mechanical ventilation. Obesity. 2020; 28(7): 1195–99.
https://doi.org/10.1002/oby.22831. PMID: 32271993. PMCID: PMC7262326.
17. Petrilli C.M., Jones S.A., Yang J. et al. Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: Prospective cohort study. BMJ. 2020; 369: m1966.
https://doi.org/10.1136/bmj.m1966. PMID: 32444366. PMCID: PMC7243801.
18. Qian Z., Li Z., Peng J. et al. Association between hypertension and prognosis of patients with COVID-19: A systematic review and meta-analysis. Clin Exp Hypertens. 2022; 44(5): 451–58.
https://doi.org/10.1080/10641963.2022.2071914. PMID: 35531646.
19. Huang L., Huang L., Yu J. et al. An association between N-terminal pro-brain natriuretic protein level and risk of left ventricular hypertrophy in patients without heart failure. Exp Ther Med. 2020; 19(5): 3259–66.
https://doi.org/10.3892/etm.2020.8598. PMID: 32266021. PMCID: PMC7132238.
20. Wang L., Chen F., Bai L. et al. Association between NT-proBNP level and the severity of COVID-19 pneumonia. Cardiol Res Pract. 2021; 2021: 5537275.
https://doi.org/10.1155/2021/5537275. PMID: 34306746. PMCID: PMC8266470.
21. Gupta Y., Maciorowski D., Medernach B. et al. Iron dysregulation in COVID-19 and reciprocal evolution of SARS-CoV-2: Natura nihil frustra facit. J Cell Biochem. 2022; 123(3): 601–19.
https://doi.org/10.1002/jcb.30207. PMID: 34997606. PMCID: PMC9015563.
22. Zheng M., Karki R., Vogel P., Kanneganti T.-D. Caspase-6 is a key regulator of innate immunity, inflammasome activation, and host defense. Cell. 2020; 181(3): 674–687.e13.
https://doi.org/10.1016/j.cell.2020.03.040. PMID: 32298652. PMCID: PMC7425208.
23. Lippi G., Mullier F., Favaloro E.J. D-dimer: Old dogmas, new (COVID-19) tricks. Clin Chem Lab Med. 2023; 61(5): 841–50.
https://doi.org/10.1515/cclm-2022-0633. PMID: 35849562.
24. Yong S.J., Halim A., Halim M. et al. Inflammatory and vascular biomarkers in post-COVID-19 syndrome: A systematic review and meta-analysis of over 20 biomarkers. Rev Med Virol. 2023; 33(2): e2424.
https://doi.org/10.1002/rmv.2424. PMID: 36708022.
25. Valencia I., Lumpuy-Castillo J., Magalhaes G. et al. Mechanisms of endothelial activation, hypercoagulation and thrombosis in COVID-19: A link with diabetes mellitus. Cardiovasc Diabetol. 2024; 23(1): 75.
https://doi.org/10.1186/s12933-023-02097-8. PMID: 38378550. PMCID: PMC10880237.
26. Вельков В.В. Постковидный синдром – длинный КОВИД. Патофизиология, риски, биомаркеры, диагноз, прогноз. Пущино: АО «ДИАКОН». 2022; 22 с. (Velkov V.V. Postcovid syndrome – long-COVID. Pathophysiology, risks, biomarkers, diagnosis, prognosis. Pushchino: DEACON. 2022; 22 pp. (In Russ.)).
27. Nishi K., Yoshimoto S., Tanaka T. et al. A potential novel treatment for chronic cough in long COVID patients: Clearance of epipharyngeal residual SARS-CoV-2 spike RNA by epipharyngeal abrasive therapy. Cureus. 2023; 15(1): e33421.
https://doi.org/10.7759/cureus.33421. PMID: 36618501. PMCID: PMC9815934.
About the Authors
Olga V. Masalkina, MD, PhD (Medicine), associate professor of the Department of internal medicine propaedeutics No. 2, Academician E.A. Wagner Perm State Medical University of the Ministry of Healthcare of Russia. Address: 614000, Perm, 26 Petropavlovskaya St.E-mail: omasalkina@mail.ru
ORCID: https://orcid.org/0009-0006-3364-0591. eLibrary SPIN: 4394-5330
Elena A. Polyanskaya, MD, Dr. Sci. (Medicine), associate professor of the Department of internal medicine propaedeutics No. 2, Academician E.A. Wagner Perm State Medical University of the Ministry of Healthcare of Russia. Address: 614000, Perm, 26 Petropavlovskaya St.
E-mail: eapolyanskaya@gmail.com
ORCID: https://orcid.org/0000-0002-3694-3647. eLibrary SPIN: 6413-8930
Natalya A. Koziolova, MD, Dr. Sci. (Medicine), professor, head of the Department of internal medicine propaedeutics No. 2, Academician E.A. Wagner Perm State Medical University of the Ministry of Healthcare of Russia. Address: 614000, Perm, 26 Petropavlovskaya St.
E-mail: nakoziolova@mail.ru
ORCID: https://orcid.org/0000-0001-7003-5186. eLibrary SPIN: 1044-0503
Anna I. Chernyavina, MD, Dr. Sci. (Medicine), associate professor of the Department of internal medicine propaedeutics No. 2, Academician E.A. Wagner Perm State Medical University of the Ministry of Healthcare of Russia. Address: 614000, Perm, 26 Petropavlovskaya St.
E-mail: anna_chernyavina@list.ru
ORCID: https://orcid.org/0000-0002-0051-6694. eLibrary SPIN: 2387-6781
Similar Articles
