Protection by melatonin in respiratory diseases: valuable information for the treatment of COVID-19

Abstract

High mortality rates in severe progression of COVID-19 are predominantly caused by pulmonary failure due to high-grade airway inflammation. As investigations on the efficacy of melatonin in this disease are still in their beginning, it may be worth-while to recall the body of evidence on protective effects in other respiratory dysfunctions, which have been studied pre-clinically and clinically. In various diseases and corresponding animal models, melatonin has been shown to be protective, mainly because of its anti-inflammatory and antioxidant properties. This was documented in pathologies as different as allergic airway inflammation, toxicologically or radiation-induced acute lung injury, respiratory disorders such as COPD, obstructive sleep apnea, neonatal respiratory distress syndrome, bronchopulmonary dysplasia and asphyxia, impaired respiration in sepsis, idiopathic pulmonary fibrosis, and pulmonary hypertension. The prevailing outcome has been protection or amelioration by melatonin, in conjunction with reduced expression and release of proinflammatory cytokines, such as IL-1β, IL-2, IL-6, IL-8, and TNFα, which was often explained by interference with toll-like receptors, inhibition of NLRP3 inflammasome activation and suppression of NF-κB signaling. In several studies, these beneficial effects were partially related to the upregulation of sirtuin-1 (SIRT1) by melatonin. The body of knowledge on melatonin’s efficacy in respiratory diseases is encouraging for the use of this powerful agent in COVID-19.

Elderly as a High-risk Group during COVID-19 Pandemic: Effect of Circadian Misalignment, Sleep Dysregulation and Melatonin Administration

“…In the context of the COVID-19 pandemic, the therapeutic potential of melatonin as an agent to counteract the consequences of COVID-19 infections due to its wideranging effects as an antioxidant, anti-inflammatory, and immunostimulant, as well as to a possible antiviral action has been advocated. This subject has been extensively reviewed elsewhere [60][61][62][63]. In light of the public health problem triggered by the spread of COVID-19 and in the face of essentially null options for prevention or treatment presently available, the use of melatonin has been proposed to possibly control the consequences of this serious disease.…”

Targeting Host Defense System and Rescuing Compromised Mitochondria to Increase Tolerance against Pathogens by Melatonin May Impact Outcome of Deadly Virus Infection Pertinent to COVID-19

“…Melatonin is a naturally occurring molecule assumed to be present in every species [ 19 ]. Due to its antioxidant, anti-inflammatory, as well as other properties [ 20 , 21 , 22 , 23 , 24 , 25 ], it has been speculated to be a promising molecule for treating COVID-19 patients [ 18 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 ], and also other deadly viral infectious diseases [ 48 , 49 , 50 , 51 ]. A small scale clinical trial has also shown promising results [ 52 ].…”

The Possible Protective Effect of Melatonin and Coenzyme Q10 on Lung Injury Induced by Bleomycin in Adult Male Albino Rats

“…This is in agreement with Genovese et al (24) who added that melatonin decreased reactive oxygen species production and non-selective melatonin receptor antagonist that prevented the apoptosis in the lung tissue. Another study confirmed that the antioxidant effect of melatonin may be due to its direct free radical detoxifying activity (25) .A recent study on the effect of melatonin in treatment of respiratory diseases of Covid 19 virus found that melatonin has a good role in reducing the release of pro-inflammatory cytokines so it is able to eliminate different high grade inflammations (26) .…”