Thalidomide for the treatment of COVID-19 pneumonia: A randomized controlled clinical trial

Authors
Babak Amra 1
Farzaneh Ashrafi 2
Mehdi Torki 3
Marzieh Hashemi 3
Mohamad Shirzadi 3
Forogh Soltaninejad 1
Somayeh Sadeghi 3
Mehrzad Salmasi 3
Ramin Sami 3
Ali Darakhshandeh 3
Maryam Nasirian 4
Samaneh Pourajam 3
1 Bamdad Respiratory and Sleep Research Center, Department of Internal Medicine, Pulmonary and Sleep Ward, Isfahan University of Medical Sciences, Isfahan, Iran
2 Department of Hematology Oncology, Isfahan University of Medical Sciences, Isfahan, Iran
3 Department of Internal Medicine, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
4 Department of Epidemiology, Isfahan University of Medical Sciences, Isfahan, Iran
Abstract
Background: Coronavirus disease 2019 has become a public health concern with a high number of fatalities. Thalidomide can target inflammatory mediators and decrease inflammation in SARS-CoV-2.
Materials and Methods: An open-label, randomized controlled trial was conducted on patients with compatible lung high-resolution computed tomography scan for COVID-19 pneumonia and moderate involvement. Childbearing-age women were excluded. A total of 20 patients in the control group receiving usual treatment were compared with 26 patients in the case group who in addition to the same regimen also received thalidomide. The primary outcome was time for clinical recovery (TTCR) and intensive-care unit (ICU) admission.
Results: From April 25 to August 8, 2020, based on the inclusion criteria, 47 patients were assigned to the study. Patients receiving thalidomide had a mean TTCR of days 5.5 (95% confidence interval [CI], 0.7–10.3), as compared with days 5.3 (95% CI, 1.7–8.9) with control (odds ratio 0.01; 95% CI, −1.58–1.59, P = 0.807). The incidence of ICU admission was 27% in the thalidomide group compared with 20% in the control group (odds ratio 3.89; 95% CI, 0.55–27.4, P = 0.425). The mean length of stay in hospital in both groups was 10 days. Progressive improvement in respiratory rate, fever, and O2 saturation during the study was seen in both groups without a significant difference between the thalidomide and control group (P > 0.05).
Conclusion: This study investigated the effects of thalidomide to treat moderate COVID-19 clinical outcomes. The results established that this drug regimen did not add more effect to usual treatment for moderate COVID-19 pneumonia.
Keywords
COVID-19
intensive-care unit (ICU)
length of stay
pneumonia
thalidomide
1.
Yang Y, Peng F, Wang R, Guan K, Jiang T, Xu G, et al. The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China. J Autoimmun 2020;109:102434.  Back to cited text no. 1
    
2.
Jin Y, Yang H, Ji W, Wu W, Chen S, Zhang W, et al. Virology, epidemiology, pathogenesis, and control of COVID-19. Viruses 2020;12:372.  Back to cited text no. 2
    
3.
Zhang W, Zhao Y, Zhang F, Wang Q, Li T, Liu Z, et al. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China. J Clin Immunol 2020;214:108393.  Back to cited text no. 3
    
4.
WHO (2020). Coronavirus Disease 2019. WHO; (2020). Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019. [Last accesed on 2020 Oct 26].  Back to cited text no. 4
    
5.
Tian S, Hu W, Niu L, Liu H, Xu H, Xiao SY. Pulmonary pathology of early-phase 2019 novel coronavirus (COVID-19) pneumonia in two patients with lung cancer. JTO 2020;15:700-4.  Back to cited text no. 5
    
6.
Channappanavar R, Perlman S. Pathogenic human coronavirus infections: Causes and consequences of cytokine storm and immunopathology. Semin Immunopathol 2017;39:529-39.  Back to cited text no. 6
    
7.
Zhou Y, Fu B, Zheng X, Wang D, Zhao C, Qi Y, et al. Pathogenic T-cells and inflammatory monocytes incite inflammatory storms in severe COVID-19 patients. Natl Sci Rev 2020;7:998-1002.  Back to cited text no. 7
    
8.
Wang H, Ma S. The cytokine storm and factors determining the sequence and severity of organ dysfunction in multiple organ dysfunction syndrome. Am J Emerg Med 2008;26:711-5.  Back to cited text no. 8
    
9.
Behrens EM, Koretzky GA. Cytokine storm syndromes: Looking toward the precision medicine era. Arthritis Rheumatol 2017;69:1135-43.  Back to cited text no. 9
    
10.
Hawkins RB, Raymond SL, Stortz JA, Horiguchi H, Brakenridge SC, Gardner A, et al. Chronic critical illness and persistent inflammation, immunosuppression, and catabolism syndrome. Front Immunol 2018;9:1511.  Back to cited text no. 10
    
11.
Bonam SR, Kaveri SV, Sakuntabhai A, Girardin L, Barry J. Adjunct immunotherapies for the management of severely Ill COVID-19 patients. Cell Rep 2020;1:100016.  Back to cited text no. 11
    
12.
Chen KH, Wang SF, Wang SY, Yang YP, Wang ML, Chiou SH, et al. Pharmacological development of the potential adjuvant therapeutic agents against coronavirus disease 2019. J Chin Med Assoc 2020;83:817.  Back to cited text no. 12
    
13.
Zhu H, Shi X, Ju D, Huang H, Wei W, Dong X. Anti-inflammatory effect of thalidomide on H1N1 influenza virus-induced pulmonary injury in mice. J Inflamm 2014;37:2091-8.  Back to cited text no. 13
    
14.
Paravar T, Lee DJ. Thalidomide: Mechanisms of action. Int Rev Immunol 2008;27:111-35.  Back to cited text no. 14
    
15.
Khalil A, Kamar A, Nemer G. Thalidomide-revisited: Are COVID-19 patients going to be the latest victims of yet another theoretical drug-repurposing?. Front Immunol 2020;11:1248.  Back to cited text no. 15
    
16.
Atrah HI. Alternative management of Covid-19 infection. Scott Med J 2020;65:72-5.  Back to cited text no. 16
    
17.
Li Y, Shi K, Qi F, Yu Z, Chen C, Pan J, et al. Thalidomide combined with short-term low-dose glucocorticoid therapy for the treatment of severe COVID-19: A case-series study. Int J Infect Dis 2021;103:507-13.  Back to cited text no. 17
Advanced Biomedical Research
Volume 2023, January
January 2023
Pages 1-7