Abstract: Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. European Journal of Pharmacology 904 (2021) 174193 Contents lists available at ScienceDirect European Journal of Pharmacology journal homepage: www.elsevier.com/locate/ejphar Full length article Evaluation of Th1 and Th2 mediated cellular and humoral immunity in patients with COVID-19 following the use of melatonin as an adjunctive treatment Abdolkarim Hosseini a, Hadi Esmaeili Gouvarchin Ghaleh b, Hossein Aghamollaei c, Mahdi Fasihi Ramandi d, Gholamhossein Alishiri c, Alireza Shahriary c, Kazem Hassanpour e, Mahdi Tat a, Gholamreza Farnoosh f, * a Applied Biotechnology Research Centre, Baqiyatallah University of Medical Sciences, Tehran, Iran Applied Virology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran c Chemical Injuries Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran d Molecular Biology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran e Sabzevar University of Medical Sciences, School of Medicine, Sabzevar, Iran f Applied Biotechnology Research Centre, Baqiyatallah University of Medical Sciences, Tehran, Iran b A R T I C L E I N F O A B S T R A C T Keywords: Melatonin COVID-19 Humoral immunity Cellular immunity T helper Adjunctive therapy Coronavirus (SARS-CoV-2) is spreading rapidly in the world and is still taking a heavy toll. Studies show that cytokine storms and imbalances in T-helper (Th)1/Th2 play a significant role in most acute cases of the disease. A number of medications have been suggested to treat or control the disease but have been discontinued due to their side effects. Melatonin, as an intrinsic molecule, possesses pharmacological anti-inflammatory and anti­ oxidant properties that decreases in concentration with age; as a result, older people are more prone to various diseases. In this study, patients who were hospitalized with a diagnosis of coronavirus disease 2019 (COVID-19) were given a melatonin adjuvant (9 mg daily, orally) for fourteen days. In order to measure markers of Th1 and Th2 inflammatory cytokines (such as interleukin (IL)-2, IL-4, and interferon (IFN)-γ) as well as the expression of Th1 and Th2 regulatory genes (signal transducer and activator of transcription (STAT)4, STAT6, GATA binding protein 3 (GATA3), and T-box expressed in T cell (T-bet)), blood samples were taken from patients at the beginning and end of the treatment. Adjuvant therapy with melatonin controlled and reduced inflammatory cytokines in patients with COVID-19. Melatonin also controlled and modulated the dysregulated genes that regulate the humoral and cellular immune systems mediated by Th1 and..