Corticosteroid Therapy in Pulmonary Sequelae of Covid-19

Summary

Introduction: The new coronavirus (SARS-CoV-2) is a virus with an intense capacity for dissemination and high mortality rate. The main cause of death is viral pneumonia, characterized as organizing pneumonia that responds to treatment with corticosteroids. After 1 month of the acute phase, 25% of patients have complete recovery from lung lesions. However, lung lesions can evolve as persistent interstitial lung disease; it is possible that this persistent disease is also responsive to corticosteroid therapy. There are no controlled and randomized studies on any treatment and its effect on the natural history of this subacute or late manifestation of COVID-19. Objective: To understand the effect of oral corticosteroid therapy in the treatment of persistent pulmonary manifestations (clinical and radiological) in patients who had moderate, severe, and critical forms of COVID-19. To understand the role of some risk factors in the development of this form of lung disease. To add information on the natural history of interstitial lung disease secondary to SARS-CoV-2 pulmonary infection. Methodology: Randomized, double-blind, placebo-controlled study of patients who had COVID-19 viral pneumonia. Patients included after 12 weeks of COVID-19 diagnosis with RT-PCR or imaging tests that confirm the infection for inclusion in the protocol 100 patients with changes in high-resolution chest tomography and diffusion spirometry, will be divided into two groups, placebo and treatment; the treatment group will receive prednisolone at a dose of 0.5 mg/kg/day for 1 month and weaning in 30 days. Clinical, laboratory, functional, and imaging evaluations will be performed at the beginning, after 3 and 6 months of treatment and monthly telephone calls. The evaluation will include a medical evaluation aimed at the cardiopulmonary assessment, arterial blood gas analysis at rest and after 6MWT; functional assessment with spirometry with measurements of FEV1, FVC, TLC, and DLCO; functional assessment during exercise with 6MWT; functionality questionnaires with SF-36, MMRC, and PCFS; and collection of laboratory tests including inflammatory markers - D-dimers, blood count, C-reactive protein and ESR, autoimmunity markers (ANA and RF), and collection of medical and laboratory history data during the acute infection to verify correlation with residual lung disease. Imaging evaluation will be performed with high-resolution chest tomography.

Timeline

Start

2021-08-10

Primary completion

2022-06-09

Completion

2022-12-12

Publications

• Background Zhao YM, Shang YM, Song WB, Li QQ, Xie H, Xu QF, Jia JL, Li LM, Mao HL, Zhou XM, Luo H, Gao YF, Xu AG. Follow-up study of the pulmonary function and related physiological characteristics of COVID-19 survivors three months after recovery. EClinicalMedicine. 2020 Aug;25:100463. doi: 10.1016/j.eclinm.2020.100463. Epub 2020 Jul 15.
• Background Wu F, Zhao S, Yu B, et al. Complete genome characterisation of a novel coronavirus associated with severe human respiratory disease in Wuhan, China. bioRxiv; 2020. DOI: 10.1101/2020.01.24.919183.
• Background Wigen J, Lofdahl A, Bjermer L, Elowsson-Rendin L, Westergren-Thorsson G. Converging pathways in pulmonary fibrosis and Covid-19 - The fibrotic link to disease severity. Respir Med X. 2020 Nov;2:100023. doi: 10.1016/j.yrmex.2020.100023. Epub 2020 Oct 9.
• Background Wells AU, Devaraj A, Desai SR. Interstitial Lung Disease after COVID-19 Infection: A Catalog of Uncertainties. Radiology. 2021 Apr;299(1):E216-E218. doi: 10.1148/radiol.2021204482. Epub 2021 Jan 26. No abstract available.
• Background van Gassel RJJ, Bels JLM, Raafs A, van Bussel BCT, van de Poll MCG, Simons SO, van der Meer LWL, Gietema HA, Posthuma R, van Santen S. High Prevalence of Pulmonary Sequelae at 3 Months after Hospital Discharge in Mechanically Ventilated Survivors of COVID-19. Am J Respir Crit Care Med. 2021 Feb 1;203(3):371-374. doi: 10.1164/rccm.202010-3823LE. No abstract available.
• Background Tse GM, To KF, Chan PK, Lo AW, Ng KC, Wu A, Lee N, Wong HC, Mak SM, Chan KF, Hui DS, Sung JJ, Ng HK. Pulmonary pathological features in coronavirus associated severe acute respiratory syndrome (SARS). J Clin Pathol. 2004 Mar;57(3):260-5. doi: 10.1136/jcp.2003.013276.
• Background Remmelink M, De Mendonca R, D'Haene N, De Clercq S, Verocq C, Lebrun L, Lavis P, Racu ML, Trepant AL, Maris C, Rorive S, Goffard JC, De Witte O, Peluso L, Vincent JL, Decaestecker C, Taccone FS, Salmon I. Unspecific post-mortem findings despite multiorgan viral spread in COVID-19 patients. Crit Care. 2020 Aug 12;24(1):495. doi: 10.1186/s13054-020-03218-5.
• Background Rai DK, Sharma P, Kumar R. Post covid 19 pulmonary fibrosis. Is it real threat? Indian J Tuberc. 2021 Jul;68(3):330-333. doi: 10.1016/j.ijtb.2020.11.003. Epub 2020 Nov 10.
• Background Ojo AS, Balogun SA, Williams OT, Ojo OS. Pulmonary Fibrosis in COVID-19 Survivors: Predictive Factors and Risk Reduction Strategies. Pulm Med. 2020 Aug 10;2020:6175964. doi: 10.1155/2020/6175964. eCollection 2020.
• Background Nusair S. Abnormal carbon monoxide diffusion capacity in COVID-19 patients at time of hospital discharge. Eur Respir J. 2020 Jul 23;56(1):2001832. doi: 10.1183/13993003.01832-2020. Print 2020 Jul.
• Background Myall KJ, Mukherjee B, Castanheira AM, Lam JL, Benedetti G, Mak SM, Preston R, Thillai M, Dewar A, Molyneaux PL, West AG. Persistent Post-COVID-19 Interstitial Lung Disease. An Observational Study of Corticosteroid Treatment. Ann Am Thorac Soc. 2021 May;18(5):799-806. doi: 10.1513/AnnalsATS.202008-1002OC.
• Background Mo X, Jian W, Su Z, Chen M, Peng H, Peng P, Lei C, Chen R, Zhong N, Li S. Abnormal pulmonary function in COVID-19 patients at time of hospital discharge. Eur Respir J. 2020 Jun 18;55(6):2001217. doi: 10.1183/13993003.01217-2020. Print 2020 Jun.
• Background Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J; ATS/ERS Task Force. Standardisation of spirometry. Eur Respir J. 2005 Aug;26(2):319-38. doi: 10.1183/09031936.05.00034805. No abstract available.
• Background Liu C, Ye L, Xia R, Zheng X, Yuan C, Wang Z, Lin R, Shi D, Gao Y, Yao J, Sun Q, Wang X, Jin M. Chest Computed Tomography and Clinical Follow-Up of Discharged Patients with COVID-19 in Wenzhou City, Zhejiang, China. Ann Am Thorac Soc. 2020 Oct;17(10):1231-1237. doi: 10.1513/AnnalsATS.202004-324OC.
• Background Kovelis D, Segretti NO, Probst VS, Lareau SC, Brunetto AF, Pitta F. Validation of the Modified Pulmonary Functional Status and Dyspnea Questionnaire and the Medical Research Council scale for use in Brazilian patients with chronic obstructive pulmonary disease. J Bras Pneumol. 2008 Dec;34(12):1008-18. doi: 10.1590/s1806-37132008001200005. English, Portuguese.
• Background Ko JJ, Wu C, Mehta N, Wald-Dickler N, Yang W, Qiao R. A Comparison of Methylprednisolone and Dexamethasone in Intensive Care Patients With COVID-19. J Intensive Care Med. 2021 Jun;36(6):673-680. doi: 10.1177/0885066621994057. Epub 2021 Feb 25.
• Background Klok FA, Boon GJAM, Barco S, Endres M, Geelhoed JJM, Knauss S, Rezek SA, Spruit MA, Vehreschild J, Siegerink B. The Post-COVID-19 Functional Status scale: a tool to measure functional status over time after COVID-19. Eur Respir J. 2020 Jul 2;56(1):2001494. doi: 10.1183/13993003.01494-2020. Print 2020 Jul.
• Background The Lancet Editors. Retraction and republication: 6-month consequences of COVID-19 in patients discharged from hospital: a cohort study. Lancet. 2023 Jun 17;401(10393):2025. doi: 10.1016/S0140-6736(23)01175-3. Epub 2023 Jun 9. No abstract available.
• Background George PM, Barratt SL, Condliffe R, Desai SR, Devaraj A, Forrest I, Gibbons MA, Hart N, Jenkins RG, McAuley DF, Patel BV, Thwaite E, Spencer LG. Respiratory follow-up of patients with COVID-19 pneumonia. Thorax. 2020 Nov;75(11):1009-1016. doi: 10.1136/thoraxjnl-2020-215314. Epub 2020 Aug 24.
• Background Faverio P, Luppi F, Rebora P, Busnelli S, Stainer A, Catalano M, Parachini L, Monzani A, Galimberti S, Bini F, Bodini BD, Betti M, De Giacomi F, Scarpazza P, Oggionni E, Scartabellati A, Bilucaglia L, Ceruti P, Modina D, Harari S, Caminati A, Valsecchi MG, Bellani G, Foti G, Pesci A. Six-Month Pulmonary Impairment after Severe COVID-19: A Prospective, Multicentre Follow-Up Study. Respiration. 2021;100(11):1078-1087. doi: 10.1159/000518141. Epub 2021 Aug 19.
• Background ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002 Jul 1;166(1):111-7. doi: 10.1164/ajrccm.166.1.at1102. No abstract available.
• Background Tradução para a língua portuguesa e validação do questionário genérico de avaliação de qualidade de vida SF-36 (Brasil SF-36) / Brazilian-Portuguese version of the SF-36. A reliable and valid quality of life outcome measure Ciconelli, Rozana Mesquita; Ferraz, Marcos Bosi; Santos, Wilton; Meinão, Ivone; Quaresma, Marina Rodrigues. Rev. bras. reumatol ; Rev. bras. reumatol;39(3): 143-50, maio-jun. 1999.
• Background Carfi A, Bernabei R, Landi F; Gemelli Against COVID-19 Post-Acute Care Study Group. Persistent Symptoms in Patients After Acute COVID-19. JAMA. 2020 Aug 11;324(6):603-605. doi: 10.1001/jama.2020.12603.
• Background Britto RR, Probst VS, de Andrade AF, Samora GA, Hernandes NA, Marinho PE, Karsten M, Pitta F, Parreira VF. Reference equations for the six-minute walk distance based on a Brazilian multicenter study. Braz J Phys Ther. 2013 Nov-Dec;17(6):556-63. doi: 10.1590/S1413-35552012005000122. Epub 2013 Nov 14.
• Background Borg G. Psychophysical scaling with applications in physical work and the perception of exertion. Scand J Work Environ Health. 1990;16 Suppl 1:55-8. doi: 10.5271/sjweh.1815.

Drugs

Indications