Glucocorticoids in the combination therapy of COVID-19
https://doi.org/10.21518/ms2022-049
Abstract
Since the early months of the SARS-CoV-2 pandemic, the understanding that severe forms of COVID-19 are associated with systemic inflammation has spurred the medical community to greater efforts to evaluate the effect of numerous anti-inflammatory and immunomodulatory therapies. Corticosteroids have a broad and non-specific anti-inflammatory action; they can interfere with mRNA transcription of inflammatory cytokines, reducing the production of inflammatory mediators. Therefore, the use of glucocorticoids will reduce the complications caused by the cytokine storm. On the other hand, immunosuppression in the respiratory epithelium may delay viral clearance and predispose to secondary infections and clinical deterioration. Therefore, WHO does not currently recommend the routine use of corticosteroids in the treatment of patients with COVID-19. The RECOVERY study showed a reduction in mortality with dexamethasone in patients with COVID-19 hypoxemia, as well as an increase in the number of days without mechanical ventilation among critically ill patients. The REMAP-CAP Committee concluded that among patients with severe COVID-19, treatment with a 7-day course of various hydrocortisone dose versus no hydrocortisone resulted in 93 and 80% chances of eliminating the need for respiratory and cardiac support for 21 days. The results of studies conducted show that there was no statistical difference between steroid use and mortality in patients with COVID-19 in the high dose group, while there was statistical difference in the medium dose group. The less 5 days group showed a strong association between reduced mortality in patients with COVID-19 and steroid use, while there were no statistically significant associations in the 5–7 days group and the more than 7 days group. Inhaled forms of corticosteroids deserve attention given their effectiveness and logical use.
About the Authors
V. V. Skvortsov
Volgograd State Medical University
Russian Federation
Russian Federation
Vsevolod V. Skvortsov, Dr. Sci. (Med.), Professor of the Department of Internal Diseases
1, Pavshikh Bortsov Square, Volgograd, 400131
A. V. Tumarenko
Volgograd State Medical University
Russian Federation
Russian Federation
Aleksander V. Tumarenko, Cand. Sci. (Med.), Associate Professor, Department of Internal Medicine
1, Pavshikh Bortsov Square, Volgograd, 400131
E. A. Malyakina
Peoples’ Friendship University of Russia
Russian Federation
Russian Federation
Ellina A. Malyakina, Clinical Resident
6, Miklukho-Maklai St., Moscow, 117198
G. I. Maljakin
Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation
Russian Federation
Georgiy I. Maljakin, Clinical Resident
8, Bldg. 2, Trubetskaya St., Moscow, 119991
References
1. Wu C., Chen X., Cai Y., Xia J., Zhou X., Xu S. et al. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020;180(7):934–943. https://doi.org/10.1001/jamainternmed.2020.0994.
2. Martinez-Guerra B.A., Gonzalez-Lara M.F., Roman-Montes C.M., TamezTorres K.M., Dardón-Fierro F.E., Rajme-Lopez S. et al. Outcomes of patients with severe and critical COVID-19 treated with dexamethasone: a prospective cohort study. Emerg Microbes Infect. 2022;11(1):50–59. https://doi.org/10.1080/22221751.2021.2011619.
3. Shuto H., Komiya K., Yamasue M., Uchida S., Ogura T., Mukae H. et al. A systematic review of corticosteroid treatment for noncritically ill patients with COVID-19. Sci Rep. 2020;10(1):20935. https://doi.org/10.1038/s41598-020-78054-2.
4. Shang L., Zhao J., Hu Y., Du R., Cao B. On the use of corticosteroids for 2019-nCoV pneumonia. Lancet. 2020;395(10225):683–684. https://doi.org/10.1016/S0140-6736(20)30361-5.
5. Meduri G.U., Bridges L., Shih M.C., Marik P.E., Siemieniuk R.A.C., Kocak M. Prolonged glucocorticoid treatment is associated with improved ARDS outcomes: analysis of individual patients’ data from four randomized trials and trial-level meta-analysis of the updated literature. Intensive Care Med. 2016;42(5):829–840. https://doi.org/10.1007/s00134-015-4095-4.
6. Villar J., Ferrando C., Martínez D., Ambrós A., Muñoz T., Soler J.A. et al. Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial. Lancet Respir Med. 2020;8(3):267–276. https://doi.org/10.1016/S2213-2600(19)30417-5.
7. Mammen M.J., Aryal K., Alhazzani W., Alexander P.E. Corticosteroids for patients with acute respiratory distress syndrome: a systematic review and meta-analysis of randomized trials. Pol Arch Intern Med. 2020;130(4):276–286. https://doi.org/10.20452/pamw.15239.
8. Mélo Silva Júnior M.L., Souza L.M.A., Dutra R.E.M.C., Valente R.G.M., Melo T.S. Review on therapeutic targets for COVID-19: insights from cytokine storm. Postgrad Med J. 2021;97(1148):391–398. https://doi.org/10.1136/postgradmedj-2020-138791.
9. Parasher A. COVID-19: Current understanding of its Pathophysiology, Clinical presentation and Treatment. Postgrad Med J. 2021;97(1147):312–320. https://doi.org/10.1136/postgradmedj-2020-138577.
10. Horby P., Lim W.S., Emberson J.R., Mafham M., Bell J.L., Linsell L. et al. Dexamethasone in Hospitalized Patients with COVID-19. N Engl J Med. 2021;384(8):693–704. https://doi.org/10.1056/NEJMoa2021436.
11. Sterne J.A.C., Murthy S., Diaz J.V., Slutsky A.S., Villar J., Angus D.C. et al. Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis. JAMA. 2020;324(13):1330–1341. https://doi.org/10.1001/jama.2020.17023.
12. Angus D.C., Derde L., Al-Beidh F., Annane D., Arabi Y., Beane A. et al. Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial. JAMA. 2020;324(13):1317–1329. https://doi.org/10.1001/jama.2020.17022.
13. Tomazini B.M., Maia I.S., Cavalcanti A.B., Berwanger O., Rosa R.G., Veiga V.C. et al. Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients With Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19: The CoDEX Randomized Clinical Trial. JAMA. 2020;324(13):1307–1316. https://doi.org/10.1001/jama.2020.17021.
14. Zhou E., Li Y., Hu D., Dai Y., Wang T., Yang C. Meta-analysis and systematic review: The administration of glucocorticoids, as a line of treatment for COVID-19 patients, could result in lowering mortality. Cogent Public Health. 2022;9(1):2059129. https://doi.org/10.1080/27707571.2022.2059129.
15. Peters M.C., Sajuthi S., Deford P., Christenson S., Rios C.L., Montgomery M.T. et al. COVID-19-related Genes in Sputum Cells in Asthma. Relationship to Demographic Features and Corticosteroids. Am J Respir Crit Care Med. 2020;202(1):83–90. https://doi.org/10.1164/rccm.202003-0821OC.
16. Milne S., Li X., Yang C.X., Leitao Filho F.S., Hernández Cordero A.I., Yang C.W.T. et al. Inhaled corticosteroids downregulate SARS-CoV-2-related genes in COPD: results from a randomised controlled trial. Eur Respir J. 2021;58(1):2100130. https://doi.org/10.1183/13993003.00130-2021.
17. Ramakrishnan S., Nicolau D.V. Jr, Langford B., Mahdi M., Jeffers H., Mwasuku C. et al. Inhaled budesonide in the treatment of early COVID-19 (STOIC): a phase 2, open-label, randomised controlled trial. Lancet Respir Med. 2021;9(7):763–772. https://doi.org/10.1016/S2213-2600(21)00160-0.
18. Yu L.M., Bafadhel M., Dorward J., Hayward G., Saville B.R., Gbinigie O. et al. Inhaled budesonide for COVID-19 in people at higher risk of adverse outcomes in the community: interim analyses from the PRINCIPLE trial. medRxiv. 2021.04.10.21254672. https://doi.org/10.1101/2021.04.10.21254672.
19. Yu L.M., Bafadhel M., Dorward J., Hayward G., Saville B.R., Gbinigie O. et al. Inhaled budesonide for COVID-19 in people at high risk of complications in the community in the UK (PRINCIPLE): a randomised, controlled, open-label, adaptive platform trial. Lancet. 2021;398(10303):843–855. https://doi.org/10.1016/S0140-6736(21)01744-X.
20. Agustí A., De Stefano G., Levi A., Muñoz X., Romero-Mesones C., Sibila O. et al. Add-on inhaled budesonide in the treatment of hospitalised patients with COVID-19: a randomised clinical trial. Eur Respir J. 2022;59(3):2103036. https://doi.org/10.1183/13993003.03036-2021.
21. Kimura H., Kurusu H., Sada M., Kurai D., Murakami K., Kamitani W. et al. Molecular pharmacology of ciclesonide against SARS-CoV-2. J Allergy Clin Immunol. 2020;146(2):330–331. https://doi.org/10.1016/j.jaci.2020.05.029.
22. Eedara B.B., Alabsi W., Encinas-Basurto D., Polt R., Ledford J.G., Mansour H.M. Inhalation Delivery for the Treatment and Prevention of COVID-19 Infection. Pharmaceutics. 2021;13(7):1077. https://doi.org/10.3390/pharmaceutics13071077.
23. Maruta H., He H. PAK1-blockers: Potential Therapeutics against COVID-19. Med Drug Discov. 2020;6:100039. https://doi.org/10.1016/j.medidd.2020.100039.
24. Matsuyama S., Kawase M., Nao N., Shirato K., Ujike M., Kamitani W. et al. The Inhaled Steroid Ciclesonide Blocks SARS-CoV-2 RNA Replication by Targeting the Viral Replication-Transcription Complex in Cultured Cells. J Virol. 2020;95(1):e01648-20. https://doi.org/10.1128/JVI.01648-20.
25. Clemency B.M., Varughese R., Gonzalez-Rojas Y., Morse C.G., Phipatanakul W., Koster D.J., Blaiss M.S. Efficacy of Inhaled Ciclesonide for Outpatient Treatment of Adolescents and Adults With Symptomatic COVID-19: A Randomized Clinical Trial. JAMA Intern Med. 2022;182(1):42–49. https://doi.org/10.1001/jamainternmed.2021.6759.
26. Zaitsev A.A., Golukhova E.Z., Mamalyga M.L., Chernov S.A., Rybka M.M., Kryukov E.V. et al. Efficacy of methylprednisolone pulse therapy in patients with COVID-19. Clinical Microbiology and Antimicrobial Chemotherapy. 2020;22(2):88–91. (In Russ.) https://doi.org/10.36488/cmac.2020.2.88-91.
27. Ruiz-Irastorza G., Pijoan J.I., Bereciartua E., Dunder S., Dominguez J., GarciaEscudero P. et al. Second week methyl-prednisolone pulses improve prognosis in patients with severe coronavirus disease 2019 pneumonia: An observational comparative study using routine care data. PLoS ONE. 2020;15(9):e0239401. https://doi.org/10.1371/journal.pone.0239401.
28. Edalatifard M., Akhtari M., Salehi M., Naderi Z., Jamshidi A., Mostafaei S. et al. Intravenous methylprednisolone pulse as a treatment for hospitalised severe COVID-19 patients: results from a randomised controlled clinical trial. Eur Respir J. 2020;56(6):2002808. https://doi.org/10.1183/13993003.02808-2020.
29. Makarova E.V., Tyurikova L.V., Lyubavina N.A. The use of systemic corticosteroids in new coronavirus infection (from the standpoint of international and Russian recommendations). Medical Almanac. 2021;(1):74–82. (In Russ.) Available at: https://www.files.pimunn.ru/almanakh/2021/веб%201-66-2021.pdf.
30. Mareev V.Yu., Orlova Ya.A., Pavlikova E.P., Matskeplishvili S.T., Krasnova T.N., Malahov P.S. et al. Steroid pulse -therapy in patients With coronAvirus Pneumonia (COVID-19), sYstemic inFlammation And Risk of vEnous thRombosis and thromboembolism (WAYFARER Study). Kardiologiya. 2020;60(6):15–29. https://doi.org/10.18087/cardio.2020.6.n1226.
Review
For citations:
Skvortsov VV, Tumarenko AV, Malyakina EA, Maljakin GI. Glucocorticoids in the combination therapy of COVID-19. Meditsinskiy sovet = Medical Council. 2023;(6):52-56. (In Russ.) https://doi.org/10.21518/ms2022-049
Views:
888
Email this article 