Abstract: Received: 14 July 2021 Revised: 11 December 2021 Accepted: 22 December 2021 DOI: 10.1002/ptr.7375 RESEARCH ARTICLE Antiinflammatory potential of nano-curcumin as an alternative therapeutic agent for the treatment of mild-to-moderate hospitalized COVID-19 patients in a placebo-controlled clinical trial Ali Asadirad1,2 | Roohangiz Nashibi3 | Ali Khodadadi1,2 Mahvash Sadeghi1,4 | Azam Aminian2,5 | Sajad Dehnavi1 1 Department of Immunology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran | Ata A Ghadiri1 | Abstract The present study conducted a placebo-controlled clinical trial to evaluate the impact of 2 Cancer, Petroleum and Environmental Pollutants Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran 3 Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran 4 Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran 5 Department of Nursing, School of Nursing and Midwifery, Ilam University of Medical Sciences, Ilam, Iran Correspondence Sajad Dehnavi, Department of Immunology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Email: sjd72dehnavi@gmail.com Funding information Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran, Grant/Award Number: U-99051 1 | nano-curcumin on the inflammatory cytokines in mild-to-moderate hospitalized COVID19 patients. A total of 60 COVID-19 patients were randomly divided into nano-curcumin and control groups, and then they received 240 mg/day nano-curcumin for 7 days. The clinical manifestation and laboratory parameters in patients were recorded on days 0 and seven. Also, SYBR Green real-time PCR and ELISA techniques were implicated in assessing the mRNA expression of IFN-γ, IL-1β, IL-6, MCP-1, and TNF-α and the serum levels of IL1β, IL-6, and TNF-α inflammatory mediators, respectively. Although the clinical manifestations and laboratory parameters improved via the nano-curcumin treatment, the mRNA expression of IFN-γ (p = 0.006) and TNF-α (p = 0.04) were significantly reduced. Besides, a considerable difference was observed between the nano-curcumin and control groups in the expression of IFN-γ (p = 0.001), IL-1β (p = 0.0002), and IL-6 (p = 0.008). In addition, there was a significant difference between the nano-curcumin and control groups in the serum levels of IL-1β (p = 0.042). The evidence demonstrated that nano-curcumin could be implicated as a complementary medication to act as an antiinflammatory agent and inhibit inflammatory complications. KEYWORDS coronavirus disease-2019, curcumin, cytokine storm, inflammatory cytokines, severe acute respiratory syndrome-coronavirus-2 I N T RO DU CT I O N throat, fatigue, headache, nasal congestion, and gastrointestinal complications (G. Li et al., 2020). Also, some symptoms such as hypoxia, Coronavirus disease-2019 (COVID-19) is a newly emerged respiratory dyspnea, and difficulty breathing may be observed in patients with viral disease caused by the new coronavirus 2019 (2019-nCoV). This severe forms. This situation requires intensive care and mechanical new virus is also called severe acute respiratory syndrome- ventilation. Approximately 15% of patients progress to acute pneumo- coronavirus-2 (SARS-CoV-2). COVID-19 is characterized as a pan- nia, and in 5% of cases, this disease is accompanied by the acute..