Evaluation of Th1 and Th2 mediated cellular and humoral immunity in patients with COVID-19 following the use of melatonin as an adjunctive treatment

Abstract

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 antioxidant 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 Th2. In this study, it was shown for the first time that melatonin can be used as a medicinal adjuvant with anti-inflammatory mechanism to reduce and control inflammatory cytokines by regulating the expression of Th1 and Th2 regulatory genes in patients with COVID-19.

Therapeutic potential of melatonin and melatonergic drugs on K18‐hACE2 mice infected with SARS‐CoV‐2

“…In this context, a very small‐scale clinical study conducted in Iran showed promising results, halving the recovery time of COVID‐19 patients who were subjected to combinatory therapy including melatonin, compared to those not treated with melatonin. 78 Larger‐scale studies in humans and further preclinical studies in animals with mechanistic evaluations would determine the effectiveness of melatonergic therapy in COVID‐19.…”

Melatonin: highlighting its use as a potential treatment for SARS-CoV-2 infection

“…While the mechanism of that suppression is not specifically known [ 68 ], it may be the result of its direct inhibition of the cytosolic oxygen sensor or related to the potent antioxidant activity of the molecule which removes the agents that stabilize HIF-1α, i.e., ROS [ 69 ]. Thus, if the prediction of Codo et al [ 64 ] is valid, which we feel it is, the inhibition of HIF-1α would contribute to a reduction in lung damage and COVID-19 severity, then the use of melatonin as a treatment of SARS-CoV-2-infected patients would be further justified [ 70 – 72 ].…”

The Importance of Sleep and Circadian Rhythms for Vaccination Success and Susceptibility to Viral Infections

“…While melatonin may be useful to align circadian rhythms, it is also known for its anti-inflammatory, immunomodulatory, and antioxidant mechanisms [ 54 ]. Two recent clinical trials have noted promising results, but also point to the need for further investigation [ 55 , 56 ]. Since melatonin has a high safety profile, a low cost, and is widely available, this may represent an interesting compound to further study in the light of viral infections and vaccination.…”