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

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.

Does Evidence Exist to Blunt Inflammatory Response by Nutraceutical Supplementation during COVID-19 Pandemic? An Overview of Systematic Reviews of Vitamin D, Vitamin C, Melatonin, and Zinc.

More than one year has passed since the first cases of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome (SARS)-CoV-2 coronavirus were reported in Wuhan (China), rapidly evolving into a global pandemic. This infectious disease has become a major public health challenge in the world. Unfortunately, to date, no specific antivirals have been proven to be effective against COVID-19, and although a few vaccines are available, the mortality rate is not decreasing but is still increasing. One therapeutic strategy has been focused on infection prevention and control measures. In this regard, the use of nutraceutical supports may play a role against some aspect of the infection, particularly the inflammatory state and the immune system function of patients, thus representing a strategy to control the worst outcomes of this pandemic. For this reason, we performed an overview including meta-analyses and systematic reviews to assess the association among melatonin, vitamin C, vitamin D, zinc supplementation and inflammatory markers using three databases, namely, MEDLINE, PubMed Central and the Cochrane Library of Systematic Reviews. According to the evidence available, an intake of 50,000 IU/month of vitamin D showed efficacy in CRP. An amount of 1 to 2 g per day of vitamin C demonstrated efficacy both in CRP and endothelial function, and a dosage of melatonin ranging from 5 to 25 mg /day showed good evidence of efficacy in CRP, TNF and IL6. A dose of 50 mg/day of elemental zinc supplementation showed positive results in CRP. Based on the data reported in this review, the public health system could consider whether it is possible to supplement the current limited preventive measures through targeted nutraceutical large-scale administration.

SARS-CoV-2 and other coronaviruses negatively influence mitochondrial quality control: beneficial effects of melatonin.

Coronaviruses (CoVs) are a group of single stranded RNA viruses, of which some of them such as SARS-CoV, MERS-CoV, and SARS-CoV-2 are associated with deadly worldwide human diseases. Coronavirus disease-2019 (COVID-19), a condition caused by SARS-CoV-2, results in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) associated with high mortality in the elderly and in people with underlying comorbidities. Results from several studies suggest that CoVs localize in mitochondria and interact with mitochondrial protein translocation machinery to target their encoded products to mitochondria. Coronaviruses encode a number of proteins; this process is essential for viral replication through inhibiting degradation of viral proteins and host misfolded proteins including those in mitochondria. These viruses seem to maintain their replication by altering mitochondrial dynamics and targeting mitochondrial-associated antiviral signaling (MAVS), allowing them to evade host innate immunity. Coronaviruses infections such as COVID-19 are more severe in aging patients. Since endogenous melatonin levels are often dramatically reduced in the aged and because it is a potent anti-inflammatory agent, melatonin has been proposed to be useful in CoVs infections by altering proteasomal and mitochondrial activities. Melatonin inhibits mitochondrial fission due to its antioxidant and inhibitory effects on cytosolic calcium overload. The collective data suggests that melatonin may mediate mitochondrial adaptations through regulating both mitochondrial dynamics and biogenesis. We propose that melatonin may inhibit SARS-CoV-2-induced cell damage by regulating mitochondrial physiology.

A network medicine approach to investigation and population-based validation of disease manifestations and drug repurposing for COVID-19.

The global coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to unprecedented social and economic consequences. The risk of morbidity and mortality due to COVID-19 increases dramatically in the presence of coexisting medical conditions, while the underlying mechanisms remain unclear. Furthermore, there are no approved therapies for COVID-19. This study aims to identify SARS-CoV-2 pathogenesis, disease manifestations, and COVID-19 therapies using network medicine methodologies along with clinical and multi-omics observations. We incorporate SARS-CoV-2 virus-host protein-protein interactions, transcriptomics, and proteomics into the human interactome. Network proximity measurement revealed underlying pathogenesis for broad COVID-19-associated disease manifestations. Analyses of single-cell RNA sequencing data show that co-expression of ACE2 and TMPRSS2 is elevated in absorptive enterocytes from the inflamed ileal tissues of Crohn disease patients compared to uninflamed tissues, revealing shared pathobiology between COVID-19 and inflammatory bowel disease. Integrative analyses of metabolomics and transcriptomics (bulk and single-cell) data from asthma patients indicate that COVID-19 shares an intermediate inflammatory molecular profile with asthma (including IRAK3 and ADRB2). To prioritize potential treatments, we combined network-based prediction and a propensity score (PS) matching observational study of 26,779 individuals from a COVID-19 registry. We identified that melatonin usage (odds ratio [OR] = 0.72, 95% CI 0.56-0.91) is significantly associated with a 28% reduced likelihood of a positive laboratory test result for SARS-CoV-2 confirmed by reverse transcription-polymerase chain reaction assay. Using a PS matching user active comparator design, we determined that melatonin usage was associated with a reduced likelihood of SARS-CoV-2 positive test result compared to use of angiotensin II receptor blockers (OR = 0.70, 95% CI 0.54-0.92) or angiotensin-converting enzyme inhibitors (OR = 0.69, 95% CI 0.52-0.90). Importantly, melatonin usage (OR = 0.48, 95% CI 0.31-0.75) is associated with a 52% reduced likelihood of a positive laboratory test result for SARS-CoV-2 in African Americans after adjusting for age, sex, race, smoking history, and various disease comorbidities using PS matching. In summary, this study presents an integrative network medicine platform for predicting disease manifestations associated with COVID-19 and identifying melatonin for potential prevention and treatment of COVID-19.

Evaluation of the efficacy and safety of Melatonin in moderately ill patients with COVID-19: A structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: We will evaluate the efficacy and safety of Melatonin, compared to the standard therapeutic regimen on clinical symptoms and serum inflammatory parameters in patients with confirmed COVID-19, who are moderately ill. TRIAL DESIGN: This is a single-center, randomized, double-blind, placebo-controlled clinical trial with a parallel-group design conducted at Shahid Mohammadi Hospital, Bandar Abbas, Iran. PARTICIPANTS: All patients admitted to Severe Acute Respiratory Syndrome Departments of Shahid Mohammadi Hospital, Bandar Abbas, Iran will be screened for the following criteria. INCLUSION CRITERIA: 1. Age ≥20 years 2. Confirmed SARS-CoV-2 diagnosis (positive polymerase chain reaction). 3. Moderate COVID-19 pneumonia (via computed tomography and or X-ray imaging), requiring hospitalization. 4. Hospitalized ≤48 hours. 5. Signing informed consent and willingness of the participant to accept randomization to any assigned treatment arm. EXCLUSION CRITERIA: 1. Underlying diseases, including chronic hypertension, diabetes mellitus, seizure, depression, chronic hepatitis, cirrhosis, and cholestatic liver diseases. 2. Severe and critical COVID-19 pneumonia. 3. Use of warfarin, corticosteroids, hormonal drugs, alcohol, other antiviral and investigational medicines, and illegal drugs (during the last 30 days). 4. History of known allergy to Melatonin. 5. Pregnancy and breastfeeding. INTERVENTION AND COMPARATOR: Intervention group: The standard treatment regimen for COVID-19, according to the Iranian Ministry of Health and Medical Education's protocol, along with Melatonin capsules at a dose of 50 mg daily for a period of seven days. CONTROL GROUP: The standard therapeutic regimen for COVID-19 along with Melatonin-like placebo capsules at a dose of one capsule daily for a period of seven days. Both Melatonin and placebo capsules were prepared at the Faculty of Pharmacy and Pharmaceutical Sciences, Hormozgan University of Medical Sciences, Bandar Abbas, Iran. MAIN OUTCOMES: The primary outcomes are the recovery rate of clinical symptoms and oxygen saturation as well as improvement of serum inflammatory parameters, including C-reactive protein, tumor necrosis factor-alpha (TNF-ɑ), interleukin-1ß (IL-1ß), and IL-6 within seven days of randomization. The secondary outcomes are the time to improve clinical and paraclinical features along with the incidence of serious adverse drug reactions within seven days of randomization. RANDOMIZATION: Included patients will be allocated to one of the study arms using block randomization in a 1:1 ratio (each block consists of 10 patients). This randomization method ensures a balanced allocation between the arms during the study. A web-based system will generate random numbers for the allocation sequence and concealment of participants. Each number relates to one of the study arms. BLINDING (MASKING): All study participants, clinicians, nurses, research coordinators, and those analyzing the data are blinded to the group assignment. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): A total of 60 patients randomized into two groups (30 in each group). TRIAL STATUS: The trial protocol is Version 1.0, August 14, 2020. Recruitment began August 22, 2020, and is anticipated to be completed by November 30, 2020. TRIAL REGISTRATION: The trial protocol has been registered in the Iranian Registry of Clinical Trials (IRCT). The registration number is " IRCT20200506047323N5 ". The registration date was 14 August 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Melatonin's Impact on Antioxidative and Anti-Inflammatory Reprogramming in Homeostasis and Disease.

There is a growing consensus that the antioxidant and anti-inflammatory properties of melatonin are of great importance in preserving the body functions and homeostasis, with great impact in the peripartum period and adult life. Melatonin promotes adaptation through allostasis and stands out as an endogenous, dietary, and therapeutic molecule with important health benefits. The anti-inflammatory and antioxidant effects of melatonin are intertwined and are exerted throughout pregnancy and later during development and aging. Melatonin supplementation during pregnancy can reduce ischemia-induced oxidative damage in the fetal brain, increase offspring survival in inflammatory states, and reduce blood pressure in the adult offspring. In adulthood, disturbances in melatonin production negatively impact the progression of cardiovascular risk factors and promote cardiovascular and neurodegenerative diseases. The most studied cardiovascular effects of melatonin are linked to hypertension and myocardial ischemia/reperfusion injury, while the most promising ones are linked to regaining control of metabolic syndrome components. In addition, there might be an emerging role for melatonin as an adjuvant in treating coronavirus disease 2019 (COVID 19). The present review summarizes and comments on important data regarding the roles exerted by melatonin in homeostasis and oxidative stress and inflammation related pathologies.

A phase II, single-center, double-blind, randomized placebo-controlled trial to explore the efficacy and safety of intravenous melatonin in patients with COVID-19 admitted to the intensive care unit (MelCOVID study): a structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: • Primary objective: to evaluate the effect of intravenous melatonin (IVM) on mortality in adult patients admitted to the intensive care unit (ICU) with COVID-19. • Secondary objectives: ◦ To evaluate the effect of IVM on ICU length of stay. ◦ To evaluate the effect of IVM on the length of mechanical ventilation (MV). ◦ To evaluate if the use of IVM is associated with an increase in the number of ventilator-free days. ◦ To evaluate if the use of IVM is associated with a reduced number of failing organs as determined by the sequential organ failure assessment (SOFA) scale. ◦ To evaluate if the use of IVM is associated with a reduction of the frequency and severity of COVID-19-associated thromboembolic phenomena. ◦ To evaluate if the use of IVM is associated with a decreased systemic inflammatory response assessed by plasma levels of ferritin, D-dimer, C-reactive protein, procalcitonin and interleukin-6. ◦ To evaluate if the use of IVM is associated with an improvement in hematologic parameters. ◦ To evaluate if the use of IVM is associated with an improvement in biochemical parameters. ◦ To evaluate if the use of IVM is associated with an improvement in blood gas analysis parameters. ◦ To evaluate adverse events during the 28 day study period. TRIAL DESIGN: Phase II, single center, double-blind, placebo-controlled randomized trial with a two-arm parallel group design and 2:1 allocation ratio. PARTICIPANTS: Only critically ill adult patients that fulfill all of the inclusion criteria and none of the exclusion criteria will be included. The study will be conducted in a mixed ICU of a publicly funded tertiary referral center in Madrid, Spain with a 30-bed capacity and 1100 admissions per year. • Inclusion criteria: ◦ Patient, family member or legal guardian has provided written Informed Consent. ◦ Age ε 18 years. ◦ Confirmed SARS-CoV-2 infection with compatible symptoms AND a positive RT-PCR. ◦ Admission to the ICU with acute hypoxemic respiratory failure attributed to SARS-CoV-2 infection. ◦ ICU length of stay of less than 7 days prior to randomization with or without MV and without signs of improvement in respiratory failure (MURRAY score at randomization greater or equal to the MURRAY score at ICU admission). • Exclusion criteria: ◦ Participant in a different COVID-19 study in which the study drug is under clinical development and hasn't been previously authorized for commercialization. ◦ Liver enzymes > 5 times the upper normal range. ◦ Chronic kidney disease with GFR < 30 mL/min/1.73 m2 (stage 4 or greater) or need for hemodialysis. ◦ Pregnancy. A pregnancy test will be performed on every woman younger than 55 years of age prior to inclusion. ◦ Terminal surgical or medical illness. ◦ Autoimmune disease. ◦ Any patient condition that can prevent the study procedures to be carried out at the treating physician's judgement. INTERVENTION AND COMPARATOR: All patients will receive standard-of-care treatment according to the current institutional protocols. In addition, patients will be randomized in a 2:1 ratio to receive: • Experimental group (12 patients): 7 days of 5 mg per Kg of actual body weight per day of intravenous melatonin every 6 hours. Maximum daily dose 500 mg per day. • Control group (6 patients): 7 days of 5 mg per Kg of actual body weight per day of intravenous identically-looking placebo every 6 hours. After 3 days of treatment, 3 intensive care physicians will evaluate the participant and decide whether or not to complete the treatment based on their clinical assessment: • If objective or subjective signs of improvement or no worsening of the general clinical condition, respiratory failure, inflammatory state or multi-organ failure are observed, the participant will continue the treatment until completion. • If an adverse effect or clinical impairment is observed that is objectively or subjectively attributable to the study drug the treatment will be stopped. MAIN OUTCOME: Mortality in each study group represented in frequency and time-to-event at day 28 after randomization RANDOMIZATION: The randomization sequence was created using SAS version 9.4 statistical software (programmed and validated macros) with a 2:1 allocation. No randomization seed was pre-specified. The randomization seed was generated using the time on the computer where the program was executed. BLINDING (MASKING): Participants, caregivers and study groups will be blinded to arm allocation. NUMBERS TO BE RANDOMIZED (SAMPLE SIZE): A total of 18 patients will be randomized in this trial: 12 to the experimental arm and 6 to the control arm. TRIAL STATUS: Protocol version 2.0, June 5th 2020. Trial status: recruitment not started. The first patient is expected to be recruited in October 2020. The last patient is anticipated to be recruited in August 2021. TRIAL REGISTRATION: EU Clinical Trials Register. Date of trial registration: 10 July 2020. URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001808-42/ES FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Clinical trial to test the efficacy of melatonin in COVID-19.

The pharmacological properties of melatonin are well known. However, there is noticeable the lack of clinical trials that confirm the efficacy, security, absence of side effects in the short and long term, and the effective doses of melatonin. This point is especially important in diseases with high morbidity and mortality including COVID-19. There is not treatment for COVID-19, and several anti-inflammatory and antiviral molecules are being tested, and different vaccines are in preparation. Although the SARS-CoV-2 pandemic is apparently improving, it is expected new resurges next fall. Thus, looking for an effective treatment of COVID-19 is mandatory. Melatonin has significant anti-inflammatory, antioxidant, and mitochondrial protective effects, and its efficacy has been demonstrated in multiple experimental models of disease and in a clinical trial in sepsis. Because COVID-19 courses with a severe septic response, multiple reviews proposing melatonin as a treatment for COVID-19 have been published. Nevertheless, there is a lack of experimental and clinical data on the use of melatonin on SARS-CoV-2 infection. Accordingly, we designed a clinical trial with an injectable formulation of melatonin for intravenous perfusion in ICU patients suffering from COVID-19 that has been just approved by the Spanish Agency of Medicines and Medical Devices (AEMPS). The trial will allow by the first time understand the doses and efficacy of melatonin against COVID-19.

A randomized multicenter clinical trial to evaluate the efficacy of melatonin in the prophylaxis of SARS-CoV-2 infection in high-risk contacts (MeCOVID Trial): A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: Primary objective: to evaluate the efficacy of melatonin as a prophylactic treatment on prevention of symptomatic SARS-CoV-2 infection among healthcare workers at high risk of SARS-CoV-2 exposure. Secondary objectives: To evaluate the efficacy of melatonin as a prophylactic treatment on prevention of asymptomatic SARS-CoV-2 infection.To evaluate the efficacy of melatonin to prevent the development of severe COVID-19 in the participants enrolled in this study who develop SARS-CoV-2 infection along the trial.To evaluate the duration of COVID-19 symptoms in participants receiving melatonin before the infection.To evaluate seroconversion timing post-symptom onset. Exploratory objectives:To compare severity of COVID-19 between men and women.To evaluate the influence of sleep and diet on prevention from SARS-CoV-2 infection.To evaluate the effect of melatonin on the incidence and characteristics of lymphopenia and increase of inflammatory cytokines related to COVID-19. TRIAL DESIGN: This is a two-arm parallel randomised double-blind controlled trial to evaluate the efficacy of melatonin versus placebo in the prophylaxis of coronavirus disease 2019 among healthcare workers. PARTICIPANTS: Inclusion Criteria: Male or female participants ≥ 18 and ≤ 80 years of age.Healthcare workers from the public and private Spanish hospital network at risk of SARS-CoV 2 infection.Not having a previous COVID19 diagnosis.Understanding the purpose of the trial and not having taken any pre-exposure prophylaxis (PrEP) including HIV PrEP from March 1st 2020 until study enrolment.Having a negative SARS-CoV 2 reverse-transcription PCR (RT-PCR) result or a negative serologic rapid test (IgM/IgG) result before randomization.Premenopausal women must have a negative urinary pregnancy test in the 7 days before starting the trial treatment.Premenopausal women and males with premenopausal couples must commit to using a high efficiency anticonceptive method. EXCLUSION CRITERIA: HIV infection.Active hepatitis B infection.Renal failure (CrCl < 60 mL/min/1.73 m2) or need for hemodialysis.Osteoporosis.Myasthenia gravis.Pre-existent maculopathy.Retinitis pigmentosa.Bradycardia (less than 50 bpm).Weight less than 40 Kg.Participant with any immunosuppressive condition or hematological disease.Treatment with drugs that may prolong QT in the last month before randomization for more than 7 days including: azithromycin, chlorpromazine, cisapride, clarithromycin, domperidone, droperidol, erythromycin, halofantrine, haloperidol, lumefantrine, mefloquine, methadone, pentamidine, procainamide, quinidine, quinine, sotalol, sparfloxacin, thioridazine, amiodarone.Hereditary intolerance to galactose, Lapp lactase deficiency or glucose or galactose malabsorption.Treatment with fluvoxamine.Treatment with benzodiazepines or benzodiazepine analogues such as zolpidem, zopiclone or zaleplon.Pregnancy.Breastfeeding.History of potentially immune derived diseases such as: lupus, Crohn's disease, ulcerative colitis, vasculitis or rheumatoid arthritis.Insulin-dependent diabetes mellitus.Known history of hypersensitivity to the study drug or any of its components.Patients that should not be included in the study at the judgment of the research team. Participants will be recruited from the following eight hospitals in Madrid, Spain: Hospital Universitario La Paz, Hospital Ramón y Cajal, Hospital Infanta Sofía, Hospital 12 de Octubre, Hospital Clínico San Carlos, Hospital Central de la defensa Gómez Ulla,Hospital de La Princesa and Hospital Infanta Leonor. INTERVENTION AND COMPARATOR: Experimental: Melatonin (Circadin®, Exeltis Healthcare, Spain): 2 mg of melatonin orally before bedtime for 12 weeks. Comparator: Identical looking placebo (Laboratorios Liconsa, Spain) orally before bedtime for 12 weeks. MAIN OUTCOMES: Number of SARS-CoV-2 (COVID-19) symptomatic infections confirmed by polymerase chain reaction (PCR) test or serologic test or according to each centre diagnosis protocol. Primary outcome will be measured until the end of treatment for each participant (until the date of the last dose taken by each patient). RANDOMISATION: Patients who meet all inclusion and no exclusion criteria will be randomised, stratified by centres, sex and age (<50 and ≥ 50 years old). The randomisation sequence was created using SAS version 9.4 statistical software (procedure 'PROC PLAN') with a 1:1 allocation. No randomisation seed was specified. The randomisation seed was generated taking the hour of the computer where the program was executed. Randomization will be done centrally through the electronic system RedCAP® in order to conceal the sequence until interventions are assigned BLINDING (MASKING): Participants, caregivers, and those assessing the outcomes are blinded to group assignment. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 450 participants are planned to be enrolled in this clinical trial, 225 in the experimental arm and 225 in the placebo arm. TRIAL STATUS: Protocol version 3.0, 17th of April 2020. Recruitment ongoing. First participant was recruited on the 21st of April 2020. The final participant is anticipated to be recruited on the 31st of May 2020. As of May 18th, 2020, a total of 312 participants have been enrolled (154 at Hospital La Paz, 85 at Hospital Infanta Sofía and 73 at Hospital 12 de Octubre). TRIAL REGISTRATION: EU Clinical Trials Register: 2020-001530-35; Date of trial registration: 13th of April 2020; https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-001530-35/ES FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Can melatonin reduce the severity of COVID-19 pandemic?

The current COVID-19 pandemic is one of the most devastating events in recent history. The virus causes relatively minor damage to young, healthy populations, imposing life-threatening danger to the elderly and people with diseases of chronic inflammation. Therefore, if we could reduce the risk for vulnerable populations, it would make the COVID-19 pandemic more similar to other typical outbreaks. Children don't suffer from COVID-19 as much as their grandparents and have a much higher melatonin level. Bats are nocturnal animals possessing high levels of melatonin, which may contribute to their high anti-viral resistance. Viruses induce an explosion of inflammatory cytokines and reactive oxygen species, and melatonin is the best natural antioxidant that is lost with age. The programmed cell death coronaviruses cause, which can result in significant lung damage, is also inhibited by melatonin. Coronavirus causes inflammation in the lungs which requires inflammasome activity. Melatonin blocks these inflammasomes. General immunity is impaired by anxiety and sleep deprivation. Melatonin improves sleep habits, reduces anxiety and stimulates immunity. Fibrosis may be the most dangerous complication after COVID-19. Melatonin is known to prevent fibrosis. Mechanical ventilation may be necessary but yet imposes risks due to oxidative stress, which can be reduced by melatonin. Thus, by using the safe over-the-counter drug melatonin, we may be immediately able to prevent the development of severe disease symptoms in coronavirus patients, reduce the severity of their symptoms, and/or reduce the immuno-pathology of coronavirus infection on patients' health after the active phase of the infection is over.