Methylprednisolone in the management of post-COVID-19 interstitial lung disease: A randomized trial (STERCOV-ILD)
Keywords:
COVID-19, hypoxemia, interstitial lung disease, methylprednisolone, vital capacityAbstract
Background and aim: Post-COVID-19 Interstitial Lung Disease (ILD) is controversial and need for treatment is unclear.The aim of this study was to investigate the efficacy of methylprednisolone in the management of post-COVID-19 ILD in comparison to standard of care.
Methods: In this multicentre, randomized controlled clinical trial, patients with post-COVID ILD were assigned to two groups: the steroid group received oral methylprednisolone at a dose of 0.5 mg/kg/day, while the control group received supportive therapy. The primary outcome was proportion of patients with functional improvement (defined as the absence of hypoxemia/desaturation during 6MWT) at twelve-weeks.
Results: A total of 229 patients with post-COVID ILD patients (124 in the steroid group and 104 in the control group) completed the study. At 12-weeks, functional improvement rate was higher in the steroid group compared to the control group (74.2% vs. 55.2%, OR:2.33 [95% CI:1.34–4.06], p=0.0041). Radiological improvement was observed in 61.3% of the steroid group compared to 46.7% of the controls (OR:1.81 [95% CI:1.07–3.06], p=0.037). The mean increase in FVC (7.2% vs 3.7%, p=0.03), 6MW distance (91 vs 41 meters, p<0.001), and SpO2 (2.33 vs 1.21, p=0.002) was significantly higher in the steroid group. Multivariate regression analysis revealed that the following variables were associated with poorer outcomes: smoking (OR:0.932 [95% CI:0.875–0.992], p=0.028), older age (OR:0.951 [95% CI:0.912-0.99], p=0.035), and severe COVID-19 (OR:0.233 [95% CI:0.068–0.799], p=0.029.
Conclusions: Methylprednisolone improved oxygen saturation, FVC, exercise capacity, and radiological resolution in patients with post-COVID-19 ILD compared to the natural course of the disease.
References
1. So M, Kabata H, Fukunaga K, Takagi H, Kuno T. Radiological and functional lung sequelae of COVID-19: a systematic review and meta-analysis. BMC Pulm Med. 2021 Dec 22;21(1):97. doi:10.1186/s12890-021-01463-0
2. Watanabe A, So M, Iwagami M, et al. One‐year follow‐up CT findings in COVID ‐19 patients: A systematic review and meta‐analysis . Respirology. 2022 Aug 12. doi:10.1111/resp.14311
3. Gentile F, Aimo A, Forfori F, et al. COVID-19 and risk of pulmonary fibrosis: the importance of planning ahead. Eur J Prev Cardiol. 2020;27(13):1442–6. doi:10.1177/2047487320932695 PubMed PMID: 32551971.
4. Yu M, Liu Y, Xu D, Zhang R, Lan L, Xu H. Prediction of the development of pulmonary fibrosis using serial thin-section ct and clinical features in patients discharged after treatment for COVID-19 pneumonia. Korean J Radiol. 2020;21(6):746–55. doi:10.3348/kjr.2020.0215 PubMed PMID: 32410413.
5. Huang W, Wu Q, Chen Z, et al. The potential indicators for pulmonary fibrosis in survivors of severe COVID-19. Journal of Infection. 2020;(xxxx). doi:10.1016/j.jinf.2020.09.027 PubMed PMID: 32998036.
6. Zhao Y miao, Shang Y min, Song W bin, et al. Follow-up study of the pulmonary function and related physiological characteristics of COVID-19 survivors three months after recovery. EClinicalMedicine. 2020;25:100463. doi:10.1016/j.eclinm.2020.100463
7. Lerum TV, Aaløkken TM, Brønstad E, et al. Dyspnoea, lung function and CT findings 3 months after hospital admission for COVID-19. European Respiratory Journal. 2021;57(4). doi:10.1183/13993003.03448-2020 PubMed PMID: 33303540.
8. Guler SA, Ebner L, Aubry-Beigelman C, et al. Pulmonary function and radiological features 4 months after COVID-19: First results from the national prospective observational Swiss COVID-19 lung study. European Respiratory Journal. 2021;57(4). doi:10.1183/13993003.03690-2020 PubMed PMID: 33419891.
9. Zhao Y, Yang C, An X, et al. Follow-up study on COVID-19 survivors one year after discharge from hospital. International Journal of Infectious Diseases. 2021 Nov 1;112:173–82. doi:10.1016/j.ijid.2021.09.017 PubMed PMID: 34520845.
10. Yüksel A, Karadoğan D, Hürsoy N, et al. Post-COVID Interstitial Lung Disease: How do We Deal with This New Entity? Balkan Med J. 2024 Sep 1;41(5):377–86. doi:10.4274/balkanmedj.galenos.2024.2024-3-82 PubMed PMID: 39192585.
11. Wells AU, Devaraj A. Residual lung disease at six-month follow-up CT after COVID-19: Clinical significance is a key issue. Radiology. Radiological Society of North America Inc.; 2021. p. E406–8. doi:10.1148/radiol.2021211284 PubMed PMID: 34313479.
12. Meiler S, Poschenrieder F, Mohr A, et al. CT findings in “Post-Covid”: residua from acute pneumonia or “Post-Covid-ILD”? Sarcoidosis Vasculitis and Diffuse Lung Diseases. 2023;40(2). doi:10.36141/svdld.v40i2.13983
13. McDonald LT. Healing after COVID-19: are survivors at risk for pulmonary fibrosis? American Journal of Physiology-Lung Cellular and Molecular Physiology. 2021 Feb 1;320(2):L257–65. doi:10.1152/ajplung.00238.2020
14. Zuo W, Zhao X, Chen YG. SARS Coronavirus and Lung Fibrosis. In: Molecular Biology of the SARS-Coronavirus. Berlin, Heidelberg: Springer Berlin Heidelberg; 2010. p. 247–58. doi:10.1007/978-3-642-03683-5_15
15. Garcia-Revilla J, Deierborg T, Venero JL, Boza-Serrano A. Hyperinflammation and Fibrosis in Severe COVID-19 Patients: Galectin-3, a Target Molecule to Consider. Front Immunol. 2020 Aug 18;11. doi:10.3389/fimmu.2020.02069
16. Merad M, Martin JC. Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nat Rev Immunol. 2020 Jun 17;20(6):355–62. doi:10.1038/s41577-020-0331-4
17. Siddiqi HK, Mehra MR. COVID-19 illness in native and immunosuppressed states: A clinical–therapeutic staging proposal. The Journal of Heart and Lung Transplantation. 2020 May;39(5):405–7. doi:10.1016/j.healun.2020.03.012
18. Stahn C, Löwenberg M, Hommes DW, Buttgereit F. Molecular mechanisms of glucocorticoid action and selective glucocorticoid receptor agonists. Mol Cell Endocrinol. 2007 Sep;275(1–2):71–8. doi:10.1016/j.mce.2007.05.019
19. Yamamoto Y, Gaynor R. Role of the NF-kB Pathway in the Pathogenesis of Human Disease States. Curr Mol Med. 2001 Jul 1;1(3):287–96. doi:10.2174/1566524013363816
20. Hermoso M, Cidlowski J. Putting the Brake on Inflammatory Responses: the Role of Glucocorticoids. IUBMB Life (International Union of Biochemistry and Molecular Biology: Life). 2003 Sep 1;55(9):497–504. doi:10.1080/15216540310001642072
21. Busillo JM, Cidlowski JA. The five Rs of glucocorticoid action during inflammation: ready, reinforce, repress, resolve, and restore. Trends in Endocrinology & Metabolism. 2013 Mar;24(3):109–19. doi:10.1016/j.tem.2012.11.005
22. Pan F, Ye T, Sun P, et al. Time Course of Lung Changes at Chest CT during Recovery from Coronavirus Disease 2019 (COVID-19). Radiology. 2020 Jun;295(3):715–21. doi:10.1148/radiol.2020200370
23. Myall KJ, Mukherjee B, Castanheira AM, et al. Persistent post–COVID-19 interstitial lung disease: An observational study of corticosteroid treatment. Ann Am Thorac Soc. 2021 May 1;18(5):799–806. doi:10.1513/AnnalsATS.202008-1002OC PubMed PMID: 33433263.
24. Mizera J, Genzor S, Sova M, et al. The effectiveness of glucocorticoid treatment in post-COVID-19 pulmonary involvement. Pneumonia. 2024 Feb 5;16(1). doi:10.1186/s41479-023-00123-7
25. Dhooria S, Chaudhary S, Sehgal IS, et al. High-dose versus low-dose prednisolone in symptomatic patients with post-COVID-19 diffuse parenchymal lung abnormalities: an open-label, randomised trial (the COLDSTER trial). European Respiratory Journal. European Respiratory Society; 2022. doi:10.1183/13993003.02930-2021 PubMed PMID: 34887325.
26. Chiscano-Camón L, Ruiz-Rodriguez JC, Ruiz-Sanmartin A, Roca O, Ferrer R. Vitamin C levels in patients with SARS-CoV-2-associated acute respiratory distress syndrome. Crit Care. 2020 Dec 26;24(1):522. doi:10.1186/s13054-020-03249-y
27. Kostorz-Nosal S, Jastrzębski D, Chyra M, Kubicki P, Zieliński M, Ziora D. A prolonged steroid therapy may be beneficial in some patients after the COVID-19 pneumonia. Eur Clin Respir J. 2021 Jan 1;8(1). doi:10.1080/20018525.2021.1945186
28. Segala FV, Sgalla G, Salvati F, et al. Adjunctive corticosteroid treatment for organizing pneumonia in COVID-19 patients with persistent respiratory failure. Respir Med. 2021 Oct;187:106571. doi:10.1016/j.rmed.2021.106571
29. Posavec AL, Kučić DC, Zagorec N, et al. Prolonged corticosteroid therapy and lung abnormalities in patients after severe COVID-19 pneumonia. Sarcoidosis Vasculitis and Diffuse Lung Diseases. 2024 Dec 1;41(4). doi:10.36141/svdld.v41i4.14331
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Aycan Yüksel, Dilek Karadoğan, Nur Hürsoy, Tahsin Gökhan Telatar, Neslihan Köse Kabil, Feride Marım, İlknur Kaya, Aslıhan Banu Er, Merve Erçelik, Demet Polat Yuluğ, Merve Yumrukuz Şenel, Ceren İlgar, Ökkeş Gültekin, Selin Çakmakcı Karakaya, Bilge Yılmaz Kara, Neslihan Özçelik, İnci Selimoğlu, Kübra Uyar Er, Abdurrahman Kotan, Hasan Veysel Keskin, Metin Akgün

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Transfer of Copyright and Permission to Reproduce Parts of Published Papers.
Authors retain the copyright for their published work. No formal permission will be required to reproduce parts (tables or illustrations) of published papers, provided the source is quoted appropriately and reproduction has no commercial intent. Reproductions with commercial intent will require written permission and payment of royalties.

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.



