Evaluation of Melatonin Levels after Covid-19 in Yakutsk Residents

The article presents the results of assessing the level of melatonin after Covid-19 in residents of Yakutsk. It was found that after the coronavirus infection, there is a decrease in the level of melatonin. Coronavirus infection affects the production of melatonin, which subsequently leads to disruption of vital rhythms.

CAN MELATONIN REDUCE THE SEVERITY OF POST-COVID-19 SYNDROME?

This short review aimed at (i) providing an update on the health benefits associated with melatonin supplementation, while (ii) considering future potential research directions concerning melatonin supplementation use relative to Coronavirus disease of 2019 (COVID-19). A narrative review of the literature was undertaken to ascertain the effect of exogenous melatonin administration on humans. Night-time melatonin administration has a positive impact on human physiology and mental health. Indeed, melatonin (i) modulates the circadian components of the sleep-wake cycle;(ii) improves sleep efficiency and mood status;(iii) improves insulin sensitivity;and (iv) reduces inflammatory markers and oxidative stress. Melatonin has also remarkable neuroprotective and cardioprotective effects and may therefore prevent deterioration caused by COVID-19. We suggest that melatonin could be used as a potential therapy in the post-COVID-19 syndrome, and therefore call for action the research community to investigate on the potential use of exogenous melatonin to enhance the quality of life in patients with post-COVID-19 syndrome.

Melatonina : bases científicas para su uso en el COVID 19

La Melatonina es una hormona que actúa facilitando la aparición del sueño fisiológico. Además presenta potentes acciónes antiinflamatoria y antioxidante, con lo que ha demostrado ya ser capaz de ejercer efectos muy beneficioso sobre las alteraciones ligadas al envejecimiento que aparecen en el sistema cardiovascular y especialmente en pulmón, donde nuestro grupo ha podido constatar un efecto protector frente a procesos de estrés oxidativo , inflamatorios y de muerte celular programada ( apoptosis).. Aunque no es una sustancia antivírica, sin embargo ha demostrado tener efectos muy positivos en algunos modelos experimentales de infección por vírus disminuyendo la carga viral y también reduciendo la oxidación y la inflamación con lo que atenúa la gravedad de la enfermedad. En el COVID 19 es capaz también de interferir en el proceso infectivo que ocurre a través de los receptores de ACE2 y de EGF pues es capaz de bloquear dichas interacciones con lo que disminuye la viremia. Concretamente reduce la actividad del inflamasoma NLRP3 con lo que bloquea la liberación masiva de citoquinas disminuyendo el proceso inflamatorio lo que supone una mejoría de la evolución de la enfermedad. Por todo ello la melatonina puede desempeñar un importante papel en el tratamiento del COVID 19.Alternate : Melatonin is a hormone that acts facilitating the appearance of physiological sleep It has also a very evident antinflammatory and antioxidant capacities that result in beneficial actions on the aging processes in the cardiovascular system and in the lungs where our group has detected a protective action against oxidative stress , inflammation and apoptosis . Although melatonin is not viricidal by itself in some models of viral infections it has demonstrated its ability to reduce viral load and also inflammation and oxidation, reducing the severity of the disease. In COVID 19 melatonin has been shown to be able to interfere with the infectious process that takes place through ACE2 and EGF receptors being able to block these interactions thus reducing viremia .It is able to block the activation of the NLRP3 inflammasome thus dramatically reducing the massive secretion of cytokines and markedly reducing hyperinflammation and apoptosis leading to a better evolution of the disease .For all these reasons melatonin could play an important role in the treatment of COVID 19.

Melatonin for prevention of acute kidney injury in patients treated with intravenous polymyxin B: a double-blind, placebo-controlled randomized clinical trial.

OBJECTIVES: To evaluate the effect of melatonin versus placebo on the incidence of acute kidney injury (AKI) in patients treated with polymyxin B. METHODS: We performed a single-centre, double-blind, randomized clinical trial (NCT03725267) of 30-mg oral melatonin versus placebo for patients treated with intravenous polymyxin B. Patients aged ≥18 years receiving polymyxin B for ≤48 hours were eligible. Melatonin or placebo pills were administered until the end of polymyxin B treatment or for a maximum of 14 days. The main outcome was any level of AKI. RESULTS: Eighty-eight patients were randomized: 44 in the melatonin group and 44 in the placebo group. The study ended prematurely because of polymyxin B shortage during the COVID-19 pandemic. The patients' mean age was 63.6 ± 17.3 years, and 60.2% of the patients were men. Forty-six (52.3%, 23 in each group) patients developed AKI during the follow-up period. The incidence rate of AKI was 81.9/1000 and 77.4/1000 patients per day in melatonin and placebo groups, respectively (hazard ratio, 1.09; 95% CI, 0.61-1.94; p 0.78). Renal failure and 30-day mortality were similar between the groups. Moreover, the incidence of AKI was not different in pre-specified sub-groups. DISCUSSION: Melatonin initiated in the first 48 hours of therapy did not reduce the incidence of AKI in patients treated with polymyxin B.

Melatonin levels are low in COVID-19 positive patients and these levels are associated with depression, death anxiety and insomnia.

In this study, we aimed to measure the melatonin levels in COVID-19 positive patients and to investigate the relationship of these levels with depression, death anxiety and insomnia. COVID-19 positive pneumonia group, COVID-19 negative pneumonia group and healthy control groups were included in the study. Melatonin ELISA kit was used. Blood samples were taken at 23:00 h (h), 02:00 h and 06:00 h. Beck Depression Inventory (BDI), Templer Death Anxiety Scale (TDAS), Insomnia Severity Index (ISI) were employed to collect data from the participants. The melatonin levels of COVID-19 positive patients at 23:00 h were lower than the control group. In addition, and the melatonin levels of COVID-19 positive patients at 02:00 h and at 06:00 h were lower than both the COVID-19 negative patient group and the control group. It was observed that the peak melatonin concentration of COVID-19 positive patients occurred at 06:00 h. BDI, TDAS and ISI scores of COVID-19 positive patients were higher than other groups. There was a negative correlation between BDI, TDAS, ISI scores of COVID-19 positive patients and their melatonin levels. The correlation between all scale scores and melatonin levels was higher at 02:00 h. Adding melatonin to the treatment of COVID-19 positive patients may be beneficial for these patients experiencing high levels of depression, anxiety and insomnia.

Efficacy and safety of oral melatonin in patients with severe COVID-19: a randomized controlled trial.

Patients with COVID-19 have shown melatonin deficiency. We evaluated the efficacy and safety of administration oral melatonin in patients with COVID-19-induced pneumonia. Patients were randomly assigned in a 1:1 ratio to receive melatonin plus standard treatment or standard treatment alone. The primary outcomes were mortality rate and requirement of IMV. The clinical status of patients was recorded at baseline and every day over hospitalization based on seven-category ordinal scale from 1 (discharged) to 7 (death). A total of 226 patients (109 in the melatonin group and 117 in the control group) were enrolled (median age; in melatonin group: 54.60 ± 11.51, in control group: 54.69 ± 13.40). The mortality rate was 67% in the melatonin group and 94% in the control group (OR; 7.75, 95% CI, 3.27-18.35, P < 0.001). The rate of IMV requirement was 51.4% in the melatonin group and 70.9% in the control group, for an OR of 2.31 (95% CI, 1.34-4.00, P < 0.001). The median number of days to hospital discharge was 15 days (13-17) in the melatonin group and 21 days (14-24) in the control group (OR; 5.00, 95% CI, 0.15-9.84, P = 0.026). Time to clinical status improvement by ≥ 2 on the ordinal scale in was 12 days (9-13) in the melatonin group and 16 days (10-19) in the control group (OR; 3.92, 95% CI, 1.69-6.14, P = 0.038). Melatonin significantly improved clinical status with a safe profile in patients with severe COVID-19 pneumonia.

Melatonin-Microbiome Two-Sided Interaction in Dysbiosis-Associated Conditions.

Melatonin is a pineal indolamine, allegedly known as a circadian rhythm regulator, and an antioxidative and immunomodulatory molecule. In both experimental and clinical trials, melatonin has been shown to have positive effects in various pathologies, as a modulator of important biochemical pathways including inflammation, oxidative stress, cell injury, apoptosis, and energy metabolism. The gut represents one of melatonin's most abundant extra pineal sources, with a 400-times-higher concentration than the pineal gland. The importance of the gut microbial community-namely, the gut microbiota, in multiple critical functions of the organism- has been extensively studied throughout time, and its imbalance has been associated with a variety of human pathologies. Recent studies highlight a possible gut microbiota-modulating role of melatonin, with possible implications for the treatment of these pathologies. Consequently, melatonin might prove to be a valuable and versatile therapeutic agent, as it is well known to elicit positive functions on the microbiota in many dysbiosis-associated conditions, such as inflammatory bowel disease, chronodisruption-induced dysbiosis, obesity, and neuropsychiatric disorders. This review intends to lay the basis for a deeper comprehension of melatonin, gut microbiota, and host-health subtle interactions.