Scientific rationale of Indian AYUSH Ministry advisory for COVID-19 prevention, prophylaxis, and immunomodulation

The current outbreak of COVID-19 is caused by the SARS-CoV-2 virus that has affected > 210 countries. Various steps are taken by different countries to tackle the current war-like health situation. In India, the Ministry of AYUSH released a self-care advisory for immunomodulation measures during the COVID-19 and this review article discusses the detailed scientific rationale associated with this advisory. Authors have spotted and presented in-depth insight of advisory in terms of immunomodulatory, antiviral, antibacterial, co-morbidity associated actions, and their probable mechanism of action. Immunomodulatory actions of advised herbs with no significant adverse drug reaction/toxicity strongly support the extension of advisory for COVID-19 prevention, prophylaxis, mitigations, and rehabilitation capacities. This advisory also emphasized Dhyana (meditation) and Yogasanas as a holistic approach in enhancing immunity, mental health, and quality of life. The present review may open-up new meadows for research and can provide better conceptual leads for future researches in immunomodulation, antiviral-development, psychoneuroimmunology, especially for COVID-19.Copyright © 2021, Institute of Korean Medicine, Kyung Hee University.

Current Evidence of Cannabidiol's Potential as an Anxiolytic Agent

This article will summarize the current knowledge and scientific evidence regarding cannabidiol as a possible pharmacological tool for anxiety disorders. Although the use of this substance in medical practice is gaining momentum, gaps can still be found in the current knowledge regarding its molecular targets, drug-to-drug interactions, efficacy in different populations, adequate dosage, duration of treatment, and correct formulation. Moreover, current evidence is still preliminary, lacking robust, blinded, and placebo-controlled clinical trials in many areas of investigation. After reading this article, readers should have a thorough understanding of the current scientific evidence regarding the use of CBD as an anxiolytic drug. [Psychiatr Ann. 2023;53(6):242–246.]

Methylene blue: a controversial diagnostic acid and medication?

A narrative review of the literature was conducted to determine if the administration of methylene blue (MB) in humans has potential risks. Studies were identified from MEDLINE, Web of Science, Scopus, and Cochrane. MB is a diagnostic substance used during some diagnostic procedures and also a part of the treatment of several diseases including methemoglobinemia, vasoplegic syndrome, fosfamide-induced encephalopathy, and cyanide intoxication, and the detection of leaks or position of parathyroid corpuscles during surgery. Although the use of MB is historically justified, and it ought to be safe, because it originated as a diagnostic material, the basic toxicological characteristics of this substance are unknown. Despite reports of severe adverse effects of MB, which could significantly exceed any possible benefits evaluated for the given indication. Therefore, the clinical use of MB currently represents a controversial problem given the heterogeneity of available data and the lack of preclinical data. This is in conflict with standards of safe use of such substances in human medicinal practice. The toxic effects of the application of MB are dose-dependent and include serious symptoms such as hemolysis, methemoglobinemia, nausea and vomitus, chest pain, dyspnoea, and hypertension. Some countries regard MB as harmful because of the resulting skin irritation and triggering of an adverse inflammatory response. MB induced serotoninergic toxicity clinically manifests as neuromuscular hyperactivity. This review aims to summarize the current understanding concerning the indications for MB administration and define the potential adverse effects of MB.

Serotonin Release Assay: Functional Assay for Heparin- and Vaccine-Induced (Immune) Thrombotic Thrombocytopenia.

The serotonin release assay (SRA) has been the gold-standard assay for detection of heparin-dependent platelet-activating antibodies and integral for the diagnosis for heparin-induced thrombotic thrombocytopenia (HIT). In 2021, a thrombotic thrombocytopenic syndrome was reported after adenoviral vector COVID-19 vaccination. This vaccine-induced thrombotic thrombocytopenic syndrome (VITT) proved to be a severe immune platelet activation syndrome manifested by unusual thrombosis, thrombocytopenia, very elevated plasma D-dimer, and a high mortality even with aggressive therapy (anticoagulation and plasma exchange). While the platelet-activating antibodies in both HIT and VITT are directed toward platelet factor 4 (PF4), important differences have been found. These differences have required modifications to the SRA to improve detection of functional VITT antibodies. Functional platelet activation assays remain essential in the diagnostic workup of HIT and VITT. Here we detail the application of SRA for the assessment of HIT and VITT antibodies.

Cyproheptadine Treatment of COVID-19-Induced Enteritis: Implications for Hyperinflammatory Phase Management

A patient presented with COVID-19-induced enteritis and colitis associated with a high D-dimer. Serotonin released by activated platelets can lead to inflammation and multiorgan failure in COVID-19 infection. Cyproheptadine blocks serotonin receptors. In light of a prior report that showed that cyproheptadine successfully treated neurologic sequelae in COVID-19, we applied this treatment to this patient. Rapid clinical improvement and reduction of D-dimer occurred after 3 doses of cyproheptadine. This inexpensive, well-Tolerated, oral medication may be applicable to treat hyperinflammatory sequelae of COVID-19 infection.Copyright © 2023 American College of Gastroent. All rights reserved.

The Future for Psychedelic Agents in the Treatment of Posttraumatic Stress Disorder

Posttraumatic stress disorder (PTSD) treatment options, including the potential use of psychedelic-assisted therapy, are reviewed. Traditional PTSD treatment remains ineffective for many, and includes, trauma focused cognitive behavioral therapy, eye movement desensitization and remodeling, and selective serotonin reuptake inhibitors. Evidence has shown that with further supportive research, psychedelic-assisted therapy may offer an alternative treatment option.

A Comparison of Pediatric Mental Health Diagnoses and Selective Serotonin Reuptake Inhibitor Prescribing Before and During the COVID-19 Pandemic.

PURPOSE: To assess the rate of mental health diagnoses and selective serotonin reuptake inhibitor (SSRI) prescribing before and during the Coronavirus Disease 2019 pandemic. METHODS: We conducted a cross-sectional study at an ambulatory pediatric clinic. A prepandemic (June 2018 to June 2019) and intrapandemic (June 2020 to June 2021) cohort were reviewed. The rate of mental health visits and new SSRI prescriptions were compared. Chi-squared analyses demonstrated a variance of statistical significance. RESULTS: From 15,414 encounters (9,791 prepandemic and 5,623 intrapandemic), 397 mental health encounters were identified. 231 (4.1%) encounters occurred during the pandemic (vs. 1.7% prepandemic) and 63 (27.3%) SSRIs were prescribed (vs. 5.4% prepandemic). Mental health encounters (prevalence ratio 2.42, 95% confidence interval, 1.99-2.95, p < .001) and SSRI prescriptions (prevalence ratio 5.03, 95% confidence interval, 2.58-9.82, p < .001) were higher during the pandemic. DISCUSSION: Our findings demonstrate increased rates of SSRI prescribing and mental health diagnoses during the Coronavirus Disease 2019 pandemic, suggesting an increased incidence of these conditions. Clinicians should be prepared to manage and screen for mental health conditions.

Effect of Exogenous Application of Tryptophan and Methyl Jasmonate on Some Metabolites and Antioxidant Activities of Feverfew

Tanacetum parthenium (L.) Schultz-Bip (feverfew) is among the important medicinal and aromatic plants due to its tryptophan (TRP), serotonin (SER), melatonin (MEL), and parthenolide (PRT) content. In recent studies, have reported TRP, MEL, and (PRT) are effective in the treatment of COVID-19, thus increasing the popularity of feverfew, which is rich in these valuable molecules. This study investigated the possible effects of exogenous foliar applications of methyl jasmonate (MeJA 0.5 mM) and TRP (20 mM) on plant TRP, SER, MEL, and PRT levels. During the pre-flowering period, endogenous TRP was measured as 128.9 mu g/mL and endogenous PRT as 1.53% mg/g in the leaves of the control group. During the flowering period, the MEL level was measured as 1.38 mu g/mL in the leaves of the TRP application group. In addition, in the pre-flowering period, MeJA-induced increases of 94.51% were determined in DPPH antioxidant activity and the total flavonoid content was 38.76 mg QE/g, whereas the highest total phenolic content of 51.63 mg GAE/g was found in flower samples of the control group. However, neither the developmental periods nor the treatments significantly affected the total phenolic content in the leaves.

COVID-19 mortality among selective serotonin reuptake inhibitor users-results from a nationwide cohort.

OBJECTIVE: To examine differences in mortality and/or severe acute respiratory syndrome between selective serotonin reuptake inhibitor- (SSRI) users and non-SSRI users up to 60 days after a positive SARS-CoV-2 real-time reverse transcription PCR test. METHODS: Retrospective cohort study including all Danish residents above the age of eighteen with a positive SARS-CoV-2 PCR test from 26 February, 2020 to 5 October, 2021. The follow-up period was 60 days. The primary outcome was all-cause mortality, and the secondary outcome was severe acute respiratory syndrome. Exposure of interest was SSRI use. Differences between SSRI users and non-users were examined with Cox regression. RESULTS: Altogether, 286,447 SARS-CoV-2 positive individuals were identified, and 7113 met the criteria for SSRI use. SSRI users had a mean age of 50.4 years, and 34% were males. Non-SSRI users had a mean age of 41.4 years, and 50% were males. Similar vaccination frequency was observed among the two groups. Sertraline was the most commonly used SSRI, followed by citalopram and escitalopram. We found 255 deaths among SSRI users (3.6%) and 2872 deaths among non-SSRI users (1.0%). SSRI use was significantly associated with increased mortality, with a hazard ratio of 1.32 (95% confidence interval, 1.16 -1.50; p 0.015), even when adjusting for age, sex, vaccination status, and comorbidities. DISCUSSION: We found significantly higher mortality when comparing SSRI users to non-SSRI users within 60 days after a positive SARS-CoV-2 PCR test. Even when considering possible residual confounding, a positive effect of SSRI intake seems highly unlikely. Our study therefore speaks against the hypothesis of repurposing SSRI drugs for COVID-19 treatment.

Case Presentation Competition, 5 Back to Basics

Serotonin syndrome associated with clozapine withdrawal and concurrent selective serotonin reuptake inhibitor (SSRI) use has previously been reported. A 56-year-old female with schizophrenia was admitted for pyrexia, rigidity, and altered mental state after her second dose of clozapine restart. She had discontinued her long-term clozapine 2 weeks prior. She developed ventilatory failure, reduced consciousness, eye deviation, and worsening rigidity, requiring ICU support. Examination showed a right upper motor neurone syndrome with absent ankle reflexes. She had raised inflammatory markers and creatine kinase. Serum neuropathy, encephalitis screen, and COVID PCR were negative. Respiratory investigations were unfruitful. MRI head and spine did not show brain or cord signal change to correlate to signs. Lumbar puncture showed a quiet CSF, negative culture, viral PCR, and encephalitis antibodies. EEG showed bihemispheric background slowing. Despite clinical improvement, repeat examination showed persistent signs. She was diagnosed with serotonin syndrome after developing a bilateral tremor. Treatment with cyproheptadine correlated with an improvement in her signs, cognitive state, and EEG. Serotonin syndrome can present with reversible neuromuscular signs. With clozapine withdrawal, it can require a prolonged time course of recovery in contrast with classical serotonin syndrome. Cyprohepta- dine can cause agranulocytosis and this delays clozapine restart.

A Multicenter Double-Blind, Placebo-Controlled Trial of Escitalopram in Children and Adolescents with Generalized Anxiety Disorder.

Objective: Generalized anxiety disorder (GAD) in children and adolescents is associated with substantial morbidity and increases the risk of future psychopathology. However, relatively few psychopharmacologic studies have examined treatments for GAD in pediatric populations, especially in prepubertal youth. Methods: Children and adolescents aged 7-17 years of age with a primary diagnosis of GAD were treated with flexibly dosed escitalopram (10-20 mg daily, n = 138) or placebo (n = 137) for 8 weeks. Efficacy measures included the Pediatric Anxiety Rating Scale (PARS) for GAD, Clinical Global Impression of Severity (CGI-S) scale, Children's Global Assessment Scale (CGAS); safety measures included the Columbia-Suicide Severity Rating Scale (C-SSRS) as well as adverse events (AEs), vital signs, and electrocardiographic and laboratory monitoring. Results: Escitalopram was superior to placebo in reducing anxiety symptoms of GAD, as seen in the difference in mean change from baseline to week 8 on the PARS severity for GAD score (least squares mean difference = -1.42; p = 0.028). Functional improvement, as reflected by CGAS score, was numerically greater in escitalopram-treated patients compared with those receiving placebo (p = 0.286), and discontinuation owing to AEs did not differ between the two groups. Vital signs, weight, laboratory, and electrocardiographic results were consistent with previous pediatric studies of escitalopram. Conclusions: Escitalopram reduced anxiety symptoms and was well tolerated in pediatric patients with GAD. These findings confirm earlier reports of escitalopram efficacy in adolescents aged 12-17 years and extend the safety and tolerability data to children with GAD aged 7-11 years. ClinicalTrials.gov Identifier: NCT03924323.

Repurposing selective serotonin reuptake inhibitors for severity of COVID-19: A population-based study.

The World Health Organization has proposed that a search be made for alternatives to vaccines for the prevention and treatment of COVID-19, with one such alternative being selective serotonin reuptake inhibitors (SSRIs). This study thus sought to assess: the impact of previous treatment with SSRI antidepressants on the severity of COVID-19 (risk of hospitalisation, admission to an intensive care unit [ICU], and mortality), its influence on susceptibility to SARS-CoV-2 and progression to severe COVID-19. We conducted a population-based multiple case-control study in a region in the north-west of Spain. Data were sourced from electronic health records. Adjusted odds ratios (aORs) and 95%CIs were calculated using multilevel logistic regression. We collected data from a total of 86,602 subjects: 3060 cases PCR+, 26,757 non-hospitalised cases PCR+ and 56,785 controls (without PCR+). Citalopram displayed a statistically significant decrease in the risk of hospitalisation (aOR=0.70; 95% CI 0.49-0.99, p = 0.049) and progression to severe COVID-19 (aOR=0.64; 95% CI 0.43-0.96, p = 0.032). Paroxetine was associated with a statistically significant decrease in risk of mortality (aOR=0.34; 95% CI 0.12 - 0.94, p = 0.039). No class effect was observed for SSRIs overall, nor was any other effect found for the remaining SSRIs. The results of this large-scale, real-world data study indicate that, citalopram, could be a candidate drug for being repurposed as preventive treatment aimed at reducing COVID-19 patients' risk of progressing to severe stages of the disease.

Post-COVID-19 fibromyalgia syndrome: A report of two case

COVID-19 is a viral infection caused by SARS-CoV-2 that primarily targets the respiratory system. COVID-19 may be followed in some patients by post-COV-ID-19 syndrome, fatigue, anxiety, and musculoskeletal pain. These symptoms may be associated with other symptoms, resulting in a constellation of symptoms consistent with fibromyalgia syndrome (FMS). Two patients were evaluated at the rheumatology outpatient clinic for diffuse persistent musculoskeletal pain after COVID-19 infection. Patients presented with generalized musculoskeletal pain, fatigue, anxiety, depression, headache, hand paresthesia, and non-restorative sleep. General examination and various laboratory investigations, including autoimmune profile and radiological investigation, were normal. After examining eighteen tender points, both patients fulfilled the 1990 ACR classification criteria for FMS. Post-COVID-19 FMS should be considered during the management of post-COVID-19 syndrome to alleviate pain and prevent worsening of symptoms during the COVID-19 pandemic.Copyright © 2022, Derman Medical Publishing. All rights reserved.

New antidepressants: monoamines and beyond

The monoamine hypothesis of depression has dominated treatment for decades, but for some with treatment-resistant depression, alternative approaches are needed. This article discusses some of the other mechanisms involved in depression and how novel treatments could address these.Copyright © 2023 Wiley Interface Ltd.

Reduced social behavior and heightened anxiety as indicators of depression in SERT knockout mice

Major depressive disorder (MDD) is the most commonly diagnosed psychiatric disorder with a 12-month prevalence rate of 6.7% (Waraich et al., 2004). Now, MDD is one of the leading causes to the global health-related burden, and its prevalence was exacerbated even more by the ramifications of the COVID-19 pandemic and its impact on individuals' mobility and health across most cultures. The link between depression and serotonin suggests that reduced 5-HT signaling is a potential risk factor in the etiology of MDD (Ruhe et al., 2007). One of the classic neurotransmitters in the central nervous system, 5-HT plays an important role in the neural transduction that involves, for example, mood and cognition. Thus, it has been the pharmacological target for effective MDD medications. Young et al. (2014) found when 5-HT levels increase, socially desirable behaviors tend to increase as well. The serotonergic system in the brain involves 5HT and SERT. Previous studies have shown a reduced role capacity of SERT impacts one's vulnerability to anxiety and depression. In this protocol, social motivation was measured in mice through a pair of open and operant conditioning paradigms. Comparisons were made between 13 SERT+/+, 16 SERT+/-, and 8 SERT-/- mice siblings from Any-maze tracking data. Results support the conclusion that SERT-/- mice displayed reduced social functioning and showed more depressive-like symptoms and social memory deficits compared to their SERT+/+ and SERT +/- siblings. This suggests the observed differences in social behavior between SERT+/+, SERT+/-, and SERT-/- mice are directly associated with changes in the SERT gene expression. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

The "Janus-like" RNA-editing machinery in innate antiviral immunity

Our innate immune systems are evolved to provide the first line of immune defense against microbial infections. A key effector component is the adenosine deaminase acting on the RNA-1 (ADAR-1)/ interferon (IFN) pathway of the innate cytoplasmic immunity that mounts rapid responses to many viral pathogens. As an RNA-editing enzyme, ADAR-1 targets viral RNA intermediates in the cytoplasmic compartment to interfere with the infection. However, ADAR-1 may also edit characteristic RNA structures of certain host genes, notably, the 5-hydroxytryptamine (serotonin) receptor 2C (5HT2CR). Dysfunction of 5-HT2CR has been linked to the pathology of several human mental conditions, such as Schizophrenia, anxiety, bipolar disorder, major depression, and the mental illnesses of substance use disorders (SUD). Thus, the ADAR-1mediated RNA editing may be either beneficial or harmful;these effects need to be tightly modulated to sustain innate antiviral immunity while restricting undesired off-target self-reactivity. In this communication, we discuss ideas and tools to identify the orphan drug candidates, including small molecules and biologics that may serve as effective modulators of the ADAR-1/IFN innate immunity and are thereby promising for use in treating or preventing SUD-and/or viral infection-associated mental illnesses.Copyright © 2023, Research Trends (P) LTD.. All rights reserved.

Effectiveness of Probiotics

Background: To evaluate the potential of probiotics in stress management caused by the Covid-19 pandemic. Material(s) and Method(s): PubMed, Elsevier, New England journal of Medicine and Google Scholar were searched for the keywords "Probiotics and stress management during the Covid pandemic" up to 30th April 2022. Result(s): Probiotics have a great potential of managing mild stress. The pandemic has brought about physical as well psychological distress and has had a negative impact on the mental health of individuals. Stress increases the risk of cardiovascular diseases, hypertension and neuropsychiatric disorders. Probiotics can be used to alleviate mental stress. Probiotics maintain ecological balance of gut and provide immunity. They also affect mood and health of host by regulating gut-brain axis of host and may be used as Psychobiotics by altering various neurotransmitters like dopamine, serotonin, adrenocorticotrophic hormone, epinephrine, norepinephrine and GABA. The use of probiotics in mild stress will help reduce the risk of adverse effects and dependence associated with the psychotropic drugs. Conclusion(s): The ongoing studies on probiotics seems to be a good solution towards stress and related problems which is rapidly increasing due to COVID-19 pandemic. Probiotics seem to be beneficial in handling stress as they alter the release of neurotransmitters reducing stress level of an individual and have a positive effect on mood. The current pandemic is likely to continue and there is a need for greater preparedness of stress management, therefore, it is essential to explore the full potential of probiotics application in stress management.Copyright © 2022 Authors.

Prevalence of SARS-CoV-2 detected through cartridge-based nucleic acid amplification test (CBNAAT) among patients of Ili and Sari in various districts of Punjab

Background: COVID-19 is an infectious disease caused by the SARSCoV-2 virus. After a December 2019 outbreak in China, the World Health Organization identified SARS-CoV-2 as a new type of coronavirus. Currently, WHO recommends detection of unique sequences of virus RNA by rRT-PCR. ICMR also recommends use of CBNAAT using Cepheid Xpert Xpress SARS-CoV2. The aim of this study is to determine the prevalence of SARS-CoV-2 detected through CBNAAT. Material & Methods: This retrospective study was conducted from July 2020 to December 2021 at VRDL, GMC, Amritsar. The study group consisted of all the patients presenting with symptoms of Influenza Like Illness (ILI) and Severe Acute Respiratory Illness (SARI) who presented to hospital. The data was collected and subjected to statistical analysis. Results: During the present study, a total of 1,259 samples were analyzed for SARS-CoV-2 by CBNAAT from July 2020 to December 2021. Out of total 1,259 cases which were included in the study, 327 cases (25.97%) were found to be SARS-CoV-2 positive while 870 cases (69.10%) were SARSCoV-2 negative and 62 cases were found to be inconclusive. 62 inconclusive samples were further tested by RT-PCR. Out of which, 15 were RT-PCR positive and 47 were RT-PCR negative. Conclusions: The COVID-19 pandemic has put forward unprecedented challenge to the public health system across countries to prepare themselves for this current crisis which included isolation, contact tracing, quarantine and enforcement of a nation wide lockdown starting 25th March, 2020.

Treatment with fluvoxamine in nonhospitalized coronavirus disease 2019 patients

Context: Fluvoxamine may have a potential immune-regulatory action and a therapeutic role in severe acute respiratory syndrome-coronavirus (SARS-CoV-2) infection that may prevent progression and/or hospitalization. Aim(s): Trial that compared fluvoxamine versus placebo in nonhospitalized adults with confirmed SARS-CoV-2 infection (mild and moderate coronavirus disease 2019 cases). Settings and design: This is a double-blinded, randomized clinical trial. Patients and Methods: The study enrolled 162 cases with positive PCR assay for SARS-CoV-2 infection and who were symptomatic within 7 days of the first dose of study medication. Statistical analysis: The demographic, clinical, and laboratory data gathered together will be tabulated and statistically analyzed. The statistical analysis of data was carried out using Excel and the SPSS programs statistical package for AQ8 Social Sciences, version 17. Quantitative data were described as median (minimum-maximum). An analysis of the data was carried out to test statistically significant differences between groups. Quantitative data were presented as mean+/-SD and the Student's t test was used to compare between two groups. Result(s): In all, 162 patients completed the study;72 patients were of mild severity;90 patients were moderate cases and each group was randomized to receive fluvoxamine or placebo besides standard care. In the mild group, no significant difference was recorded while slight significance exists in the moderate severity group. Conclusion(s): Fluvoxamine may have an added value besides the current standard care in reducing the need for hospitalization in outpatient cases, especially pneumonic ones;however, more larger studies are needed. Copyright © 2023 The Egyptian Journal of Chest Diseases and Tuberculosis.