Possible Application of Melatonin in Long COVID.

Clinical sequelae and symptoms for a considerable number of COVID-19 patients can linger for months beyond the acute stage of SARS-CoV-2 infection, "long COVID". Among the long-term consequences of SARS-CoV-2 infection, cognitive issues (especially memory loss or "brain fog"), chronic fatigue, myalgia, and muscular weakness resembling myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are of importance. Melatonin may be particularly effective at reducing the signs and symptoms of SARS-CoV-2 infection due to its functions as an antioxidant, anti-inflammatory, and immuno-modulatory agent. Melatonin is also a chronobiotic medication effective in treating delirium and restoring the circadian imbalance seen in COVID patients in the intensive care unit. Additionally, as a cytoprotector, melatonin aids in the prevention of several COVID-19 comorbidities, including diabetes, metabolic syndrome, and ischemic and non-ischemic cardiovascular diseases. This narrative review discusses the application of melatonin as a neuroprotective agent to control cognitive deterioration ("brain fog") and pain in the ME/CFS syndrome-like documented in long COVID. Further studies on the therapeutic use of melatonin in the neurological sequelae of SARS-CoV-2 infection are warranted.

The prevalence and severity of insomnia symptoms during COVID-19: A global systematic review and individual participant data meta-analysis.

INTRODUCTION: There have been no previous meta-analytic studies that have looked at the prevalence of insomnia symptoms in different COVID-19 groups using a single assessment instrument to evaluate insomnia symptoms while maintaining data homogeneity. The current review's associated goal is to undertake an individual participant data (IPD) analysis to further investigate past meta-analyses, a method that has been shown to be more robust than standard meta-analyses. MEETHODS: Only studies that used the Insomnia Severity Index (ISI) to assess insomnia are used in this analysis. The IPDMA was performed and registered in PROSPERO in compliance with the PRISMA IPD Statement (CRD42021275817). From November 2019 to August 2021, researchers explored seventeen databases and six preprint services for relevant studies. RESULTS: The pooled estimate of insomnia symptoms (subthreshold and clinically significant) was 52.57%. An estimated 16.66% of the population suffered from clinically significant insomnia, of which 13.75% suffered from moderate insomnia, and 2.50% suffered from severe insomnia. The different populations' grouping had no statistically significant differences in the prevalence of insomnia symptoms. Insomnia symptoms did not appear to be associated with age or sex. CONCLUSION: Our findings imply that the COVID-19 pandemic is linked to a significant rise in subthreshold insomnia symptoms, but not to moderate or severe insomnia. Educating people from all walks of life about the importance of sleep and the risk of acquiring insomnia symptoms during this or future pandemics should be a top concern.

Prevalence and risk factors of self-reported psychotic experiences among high school and college students: A systematic review, meta-analysis, and meta-regression.

BACKGROUND: Adolescents are at high risk of incident psychopathology. Fleeting psychotic experiences (PEs) that emerge in young people in response to stress may be warning signs that are missed by research that fails to study stressed populations, such as late high school and college/university students. Our aim in this systematic review was to conduct a meta-analysis that estimates prevalence rates of PEs in students, and to assess whether these rates differ by gender, age, culture, and COVID-19 exposure. METHOD: We searched nine electronic databases, from their inception until January 31, 2022 for relevant studies. We pooled the estimates using the DerSimonian-Laird technique and random-effects meta-analysis. Our main outcome was the prevalence of self-reported PEs in high school and college/university students. We subsequently analyzed our data by age, gender, population, country, culture, evaluation tool, and COVID-19 exposure. RESULTS: Out of 486 studies retrieved, a total of 59 independent studies met inclusion criteria reporting 210' 024 students from 21 different countries. Nearly one in four students (23.31%; 95% CI 18.41%-29.05%), reported having experienced PEs (heterogeneity [Q = 22,698.23 (62), p = 0.001] τ2  = 1.4418 [1.0415-2.1391], τ = 1.2007 [1.0205-1.4626], I2  = 99.7%, H = 19.13 [18.59-19.69]). The 95% prediction intervals were 04.01%-68.85%. Subgroup analyses showed that the pooled prevalence differed significantly by population, culture, and COVID-19 exposure. CONCLUSION: This meta-analysis revealed high prevalence rates of self-reported PEs among teen and young adult students, which may have significance for mental health screening in school settings. An important realization is that PEs may have very different mental health meaning in different cultures.

The Origin and Clinical Relevance of Yoga Nidra.

Yoga nidra, also known as 'yogic sleep', is a simplified form of an ancient tantric relaxation technique. The most general description of the practice is that it combines guided mental imagery with a specific yoga posture called Shavasana (or "corpse pose"). The goal of yoga nidra is to promote a profound state of relaxation, which differs from sleep inasmuch as there is still an awareness of one's surroundings. While several components of the practice have been known since ancient times, it was not until the 1960s that an updated and systematized system of practice was introduced to the public through the writings of Swami Satyananda Saraswati. Unlike other schools of yoga, which emphasize concentration or contemplation, yoga nidra's goal is complete relaxation. As such, its advocates claim that it is suitable for all individuals, from beginners to advanced practitioners of yoga. The calm inner stillness induced by yoga nidra is claimed by practitioners to be an effective stress management tool as well as a means for attaining greater receptivity to personal resolutions. These resolutions can range from the goal of achieving self-transformation, enhancing creativity, or improving one's learning ability. Additionally, yoga nidra is claimed to promote beneficial changes in physiological and mental health. The following narrative review summarizes the basic steps used to achieve the final state of yoga nidra relaxation as well as some recent experimental findings regarding its physiological and psychological effects. Standard research databases were searched for relevant articles. Clinical studies have shown that yoga nidra meditation is associated with positive physiological changes, including improvements in several hematological variables, red blood cell counts, blood glucose levels, and hormonal status. Two neuroimaging studies have shown that yoga nidra produces changes in endogenous dopamine release and cerebral blood flow, a further confirmation that its effects on the CNS are objectively measurable. The practice has also been shown to reduce psychometrically measured indices of mild depression and anxiety, although these benefits were not shown in an experimental study to extend to severe depression or severe anxiety.

Neuropsychiatric Consequences of COVID-19 Pandemic: A Synthetic Review from a Global Perspective.

Some research suggests that distress, secondary to isolation and fear following COVID-19 infection, can negatively affect the long-term more than the COVID-19 infection itself. This narrative review aims to provide a global view on the neuropsychiatric consequences of COVID-19 that can be ascribed to several factors, ranging from the direct effect of infection, to the body's responses against the infection, or to the psychological sequelae of social isolation, unemployment, and fear for one's health and livelihood. Current findings show that the more severe the respiratory infection, the more likely are central nervous system (CNS) complications regarding the infection itself. The immune reactions to the infection may result in symptoms similar to chronic fatigue as well as neurocognitive deficits, which last long after the infection is gone. An increase in symptoms of depression, anxiety, and trauma-related stress may also follow upon economic fears and isolation from friends and family. The consequences of the pandemic are not limited to adults; children learning remotely and away from classmates and routine activities may develop adjustment disorders, acute stress disorder, and a variety of manifestations of grief. A summary of case reports suggests that COVID-19-related stress, economic recession, and political unrest increase the risk of suicidal behaviors and acts of violence. However, it is unknown whether manifestations of mental disorders result from social causes or whether CNS complications may be responsible.

Sleep disturbances during the COVID-19 pandemic: A systematic review, meta-analysis, and meta-regression.

This systematic review and meta-analysis evaluated the extent of sleep disturbances during the COVID-19 pandemic. Eleven databases and six preprint repositories were searched for the period from November 1, 2019, to July 15, 2021. The DerSimonian and Laird method was used to develop random-effect meta-analyses. Two hundred and fifty studies comprising 493,475 participants from 49 countries were included. During COVID-19, the estimated global prevalence of sleep disturbances was 40.49% [37.56; 43.48%]. Bayesian meta-analysis revealed an odds of 0.68 [0.59; 0.77] which translates to a rate of approximately 41%. This provides reassurance that the estimated rate using classical meta-analysis is robust. Six major populations were identified; the estimated prevalence of sleep problem was 52.39% [41.69; 62.88%] among patients infected with COVID-19, 45.96% [36.90; 55.30%] among children and adolescents, 42.47% [37.95; 47.12%] among healthcare workers, 41.50% [32.98; 50.56%] among special populations with healthcare needs, 41.16% [28.76; 54.79%] among university students, and 36.73% [32.32; 41.38%] among the general population. Sleep disturbances were higher during lockdown compared to no lockdown, 42.49% versus 37.97%. Four in every ten individuals reported a sleep problem during the COVID-19 pandemic. Patients infected with the disease, children, and adolescents appeared to be the most affected groups.

Melatonin as an Add-On Treatment of COVID-19 Infection: Current Status.

This brief review was written to provide a perspective on the flurry of reports suggesting that melatonin can be an important add-on therapy for COVID-19. Despite the passage of more than 60 years since its discovery and much evidence representing the contrary, there has been great reluctance to conceive melatonin as anything other than a hormone. Many other body chemicals are known to have multiple roles. Melatonin was first shown to be a hormone derived from the pineal gland, to be actively synthesized there only at night, and to act on targets directly or via the G-protein-coupled receptors (GPCRs) superfamily. It is of note that over 40 years ago, it was also established that melatonin is present, synthesized locally, and acts within the gastrointestinal tract. A wider distribution was then found, including the retina and multiple body tissues. In addition, melatonin is now known to have non-hormonal actions, acting as a free radical scavenger, an antioxidant, and as modulating immunity, dampening down innate tissue responses to invaders while boosting the production of antibodies against them. These actions make it a potentially excellent weapon against infection by the SARS-CoV-2 virus. Early published results support that thesis. Recently, a randomized controlled study reported that low doses of melatonin significantly improved symptoms in hospitalized COVID-19 patients, leading to more rapid discharge with no side effects, while significantly decreasing levels of CRP, proinflammatory cytokines, and modulating dysregulated genes governing cellular and humoral immunity. It is now critical that these trials be repeated, with dose-response studies conducted and safety proven. Numerous randomized controlled trials are ongoing, which should complete those objectives while also allowing for a more thorough evaluation of the mechanisms of action and possible applications to other severe diseases.

'Distant socializing,' not 'social distancing' as a public health strategy for COVID-19.

Social distancing, also referred to as physical distancing, means creating a safe distance of at least two meters (six feet) between yourself and others. This is a term popularized during the COVID-19 pandemic, as it is one of the most important measures to prevent the spread of this virus. However, the term 'social distancing' can be misleading, as it may imply that individuals should stop socializing. However, socializing in a safe context (i.e. over the phone, video-chat, etc.) is especially important during this time of crisis. Therefore, in this narrative review, we suggest the term 'distant socializing' as more apt expression, to promote physical distancing measures while also highlighting the importance of maintaining social bonds. Further, articles discussing the practice, implementation, measurement, and mental health effects of physical distancing are reviewed. Physical distancing is associated with psychiatric symptoms (such as anxiety and depression), suicidal ideation, and domestic violence. Further, unemployment and job insecurity have significantly increased during COVID-19, which may exacerbate these negative mental health effects. Governments, medical institutions, and public health bodies should therefore consider increasing mental health resources both during and after the pandemic, with a specific focus on frontline workers, COVID-19 survivors, and marginalized communities.

Strategy for COVID-19 vaccination in India: the country with the second highest population and number of cases.

Free vaccination against COVID-19 commenced in India on January 16, 2021, and the government is urging all of its citizens to be immunized, in what is expected to be the largest vaccination program in the world. Out of the eight COVID-19 vaccines that are currently under various stages of clinical trials in India, four were developed in the country. India's drug regulator has approved restricted emergency use of Covishield (the name employed in India for the Oxford-AstraZeneca vaccine) and Covaxin, the home-grown vaccine produced by Bharat Biotech. Indian manufacturers have stated that they have the capacity to meet the country's future needs for COVID-19 vaccines. The manpower and cold-chain infrastructure established before the pandemic are sufficient for the initial vaccination of 30 million healthcare workers. The Indian government has taken urgent measures to expand the country's vaccine manufacturing capacity and has also developed an efficient digital system to address and monitor all the aspects of vaccine administration.

Autism Spectrum Disorder patients may be susceptible to COVID-19 disease due to deficiency in melatonin.

Patients with Autism Spectrum Disorder (ASD) may be particularly prone to develop COVID-19. An unusual extended course of COVID-19 disease illness has been reported in one ASD patient and a group of patients have COVID-19 disease in a neurodevelopmental facility. It has been widely reported that many of those with ASD have substantial sleep disorders with low levels of melatonin and various genetic alterations related to melatonin production have been found. Several lines of evidence point to a substantial role of melatonin in the body's innate defense system including acting as a scavenger, an antioxidant and modulating the immune system. We therefore hypothesize that melatonin deficiency may predispose those ASD patients who have low melatonin output to COVID-19 disease. Potential implications for treatment are discussed.

Addressing psychological resilience during the coronavirus disease 2019 pandemic: a rapid review.

PURPOSE OF REVIEW: The mental health toll on populations exposed to COVID-19 is alarming, and there is a need to address this with urgency. This current review provides insights on how individuals, communities, and specific populations, such as healthcare workers and patients are leveraging pre-COVID-19 and peri-COVID-19 factors to reinforce their psychological resilience during the global public health crisis. RECENT FINDINGS: Examination of the extant literature indicated that populations around the world rely often on support from their loved-ones, closed significant others, outdoor and physical activities, and spirituality to cope with the COVID-19-related distress. Increased sense of meaning/purpose since the COVID-19 pandemic was also reported. SUMMARY: A portion of publications provided intervention models to reinforce resilience among specific populations during the COVID-19 pandemic. Nevertheless, it is not convincing that some of these models can be applied universally. Additionally, it is important to note that in this category, translational data was scarce.

Can Melatonin Be a Potential "Silver Bullet" in Treating COVID-19 Patients?

The therapeutic potential of melatonin as a chronobiotic cytoprotective agent to counteract the consequences of COVID-19 infections has been advocated. Because of its wide-ranging effects as an antioxidant, anti-inflammatory, and immunomodulatory compound, melatonin could be unique in impairing the consequences of SARS-CoV-2 infection. Moreover, indirect evidence points out to a possible antiviral action of melatonin by interfering with SARS-CoV-2/angiotensin-converting enzyme 2 association. Melatonin is also an effective chronobiotic agent to reverse the circadian disruption of social isolation and to control delirium in severely affected patients. As a cytoprotector, melatonin serves to combat several comorbidities such as diabetes, metabolic syndrome, and ischemic and non-ischemic cardiovascular diseases, which aggravate COVID-19 disease. In view of evidence on the occurrence of neurological sequels in COVID-19-infected patients, another putative application of melatonin emerges based on its neuroprotective properties. Since melatonin is an effective means to control cognitive decay in minimal cognitive impairment, its therapeutic significance for the neurological sequels of SARS-CoV-2 infection should be considered. Finally, yet importantly, exogenous melatonin can be an adjuvant capable of augmenting the efficacy of anti-SARS-CoV-2 vaccines. We discuss in this review the experimental evidence suggesting that melatonin is a potential "silver bullet" in the COVID 19 pandemic.

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

The association of age with a higher vulnerability to COVID-19 infection is a subject of major importance. Several factors, including higher stress due to social isolation, diminished melatonin levels with age, and higher exposure of individuals to light at the evening, which reduces melatonin levels and disrupts circadian rhythmicity are relevant for maintaining the circadian health in aged individuals. Properly administered, chronotherapy restores the optimal circadian pattern of the sleep-wake cycle in the elderly. It involves adequate sleep hygiene, timed light exposure, and the use of a chronobiotic medication like melatonin, which affects the output phase of circadian rhythms thus controlling the biological clock. Besides, the therapeutic potential of melatonin as an agent to counteract the consequences of COVID-19 infections has been advocated due to its wide-ranging effects as an antioxidant, anti-inflammatory, and as an immunomodulatory agent, as well as to a possible antiviral action. This article discusses how chronotherapy may reverse the detrimental circadian condition of the elderly in the COVID-19 pandemic.