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.

Alterations of Monoaminergic Systems in Alzheimer’s Disease: A Traditional Review

Alzheimer’s disease (AD) is an age-related, neurodegenerative disease with characteristic clinical and pathological features. The death rate from AD was exacerbated by the coronavirus disease 2019 pandemic in 2020. The most common neuropathological findings are extraneuronal senile plaques and intraneuronal neurofibrillary tangles. AD is a multisystemic disease that affects many neuronal structures, including monoaminergic systems. Functional changes in neurotransmitters are closely related to the pathophysiology of AD. It is known that many neurotransmitters such as acetylcholine decrease as a result of loss of neuronal synapses and neuronal death. In the monoaminergic system, basically, the substantia nigra nucleus providing the dopaminergic innervation, the dorsal raphe nucleus providing the serotonergic innervation, the locus ceruleus nucleus providing the noradrenergic innervation, and the tuberomamillar nucleus providing the histaminergic innervation are exposed to significant degeneration in AD. There are changes in the levels of relevant neurotransmitters in the regions projected from these nuclei. Combined therapy (cognitive enhancing treatments, drugs to treat neuropsychiatric symptoms, disease-modifying therapies) important to reduce behavioral abnormalities and effectively restore cognitive functions in AD patients. Treatment strategies for AD require understanding the molecular mechanism behind the monoaminergic system. With this traditional review, we aim to discuss in detail the changes that occur in the monoaminergic system, especially in dopamine, noradrenaline, serotonin and histamine mechanisms in AD, and present a perspective on this issue. As a result;more studies in humans and animal models are needed to better understand the signaling mechanism of the monoaminergic system and the effects of monoaminergic receptors. Thus, the development of new treatment strategies for AD will accelerate. © 2022 by Türkiye Klinikleri.

The Significant Role of the Sympathetic Nervous System in Hospitalization and Death of Patients With COVID-19: Psycho-Neuroendocrine-Immune Aspect of Stress

The primary immune responses to CoV-19 are inter-individual variability against this virus. Studies on the neuro-immune system demonstrate that interactions in these communication pathways can be a reason for several psychiatric disorders and immune-mediated diseases. Stress-related behaviors are significant in the psycho-immune interactions, and even stress-related factors such as socioeconomic status can also play a vital role in these interactions. A literature review on the topic was carried out, and 150 articles were included. Catecholamine and glucocorticoids are stress neurohormones. Noradrenaline as signaling molecules, through macrophages, can be an essential stimulus for cytokine secretion. Glucocorticoids, by both pro-and anti-inflammatory roles in specific conditions, can inhibit the elevation of the inflammatory response by inhibiting the pro-inflammatory macrophage activation and also enhance the anti-inflammatory activity in monocyte/macrophage populations the further eliminate. Stress with this flawed amplification feedback system can disrupt immune homeostasis (cytokine storm) in the patient with COVID-19. This investigation showed that there is a strong link between psycho-neuroendocrine-immune axis organizations against respiratory viral infections during the COVID-19 epidemic. The stress cascade must be responsible for meeting the body's hemostatic challenges in the necessary physiological and metabolic interactions. The motivation of the stress system leads to behavioral/physical variations that are strangely consistent in their qualitative presentation. These variations must be generally adaptive and increase the chances of the individual's survival. In coronavirus respiratory disease, identifying people with acute/chronic psychosocial stress is of particular importance for providing prompt care as soon as possible, as scheduling intervention appears to be an essential factor in reducing stress and hospitalization rate in the intensive care unit (ICU). Copyright © 2022 Tehran University of Medical Sciences. All rights reserved.

ACE2 Inhibitor MLN-4760 Enhances Noradrenalin-induced Contraction and Stimulates Endothelium-dependent Contraction of Femoral Arteries: the Benefit of Taxifolin Treatment

The importance of disclosing the various effects of the inhibition of angiotensin-converting enzyme-2 (ACE2) in regulation of vascular tone has been shown during the COVID-19 pandemic. Various substances with antioxidant properties were proposed to have a beneficial effect in mitigating the progress of COVID-19. Therefore, we have investigated the effect of 14-day ACE2 inhibitor MLN-4760 treatment (s.c.) and 10-day oral coadministration of taxifolin (TAX) on the regulation of vascular tone of isolated femoral arteries. Our results showed that the ACE2 inhibitor MLN-4760 enhanced the maximal noradrenalin-induced contraction as well as the sensitivity to noradrenalin (NA). The acetylcholine-induced endothelium-dependent relaxation was not changed after MLN-4760 administration, but the acetylcholine-induced endothelium-dependent contraction was augmented. TAX administration reduced the maximal NA-induced contraction, but did not change the sensitivity to NA. The endothelium-dependent relaxation was improved after TAX application as shown by the calculation of area under the curve. TAX did not influence the acetylcholine-induced endothelium-dependent contraction. In conclusion, administration of MLN-4760 leads to increased NA-induced contraction of femoral arteries, which can be partially mediated through increased endotheliumdependent contraction. TAX mitigated the enhanced NA-induced contraction caused by MLN-4760 administration, but did not affect endothelium-dependent contraction. [ FROM AUTHOR] Copyright of Acta Facultatis Pharmaceuticae Universitatis Comenianae is the property of Sciendo and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Intravenous vitamin C administration to patients with septic shock: a pilot randomised controlled trial.

BACKGROUND: Intravenous vitamin C administration in septic shock may have a sparing effect on vasopressor requirements, and vitamin C's enzyme cofactor functions provide a mechanistic rationale. Our study aimed to determine the effect of intravenous vitamin C administration on vasopressor requirements and other outcomes in patients with septic shock. METHODS: This was a double-blind, randomised placebo-controlled trial in 40 patients with septic shock who were randomised (1:1) to receive intravenous vitamin C (at a dose of 25 mg/kg of body weight every 6 h) or placebo (intravenous 5% dextrose) for up to 96 h, or until death or discharge. The primary outcome was intravenous vasopressor requirements (dose and duration), and secondary outcomes included Sequential Organ Failure Assessment (SOFA) scores, intensive care unit (ICU) and hospital length of stay, and mortality. In addition, blood samples were collected to determine vitamin C kinetics and inflammatory marker concentrations. RESULTS: Median plasma vitamin C concentrations were deficient at baseline (9.2 [4.4, 12] µmol/L) and increased to 408 (227, 560) µmol/L following 72 h of intervention. The mean duration of intravenous vasopressor infusion in the vitamin C group was 48 (95% CI 35-62) hours and in the placebo group was 54 (95% CI 41-62) hours (p = 0.52). The dose of vasopressor delivered over time was comparable between the two groups, as were SOFA scores (p > 0.05). The median ICU length of stay in the intervention group was 3.8 (2.2, 9.8) days versus 7.1 (3.1, 20) days in the placebo group (p = 0.12). The median hospital length of stay for the vitamin C group was 18 (11, 35) days versus 22 (10, 52) days for the placebo group (p = 0.65). Mortality was comparable between the two groups (p > 0.05). Of the inflammatory markers, neutrophil counts were elevated in the vitamin C group relative to placebo by 72 h (p = 0.01). C-reactive protein and myeloperoxidase concentrations were elevated at baseline, however, the two groups were comparable over time (p > 0.05). CONCLUSIONS: Our pilot study indicated that intravenous vitamin C did not provide significant decreases in the mean dose or duration of vasopressor infusion. Further research that takes into account the potential impact of intervention timing, dose and duration, and location of trial, may provide more definitive evidence. TRIAL REGISTRATION: ACTRN12617001184369 (11/8/2017).

An analysis of antidepressant prescribing trends in England 2015-2019.

Background Growing concerns about the impact of coronavirus disease 2019 (COVID-19) will likely lead to increased mental health diagnoses and treatment. To provide a pre-COVID-19 baseline, we have examined antidepressant prescribing trends for 5 years preceding COVID-19. Methods A retrospective analysis of anonymised data on medicines prescribed by GPs in England from the Open-Prescribing Database (January 2015 to December 2019) identified the 10 most prescribed antidepressant and, for comparison, cardiovascular medicines. Results Prescription items for the 10 most prescribed antidepressants rose 25% from 58 million (2015) to 72 million (2019). Citalopram was the most prescribed antidepressant; prescriptions for sertraline rose fastest at 2 million items year on year. Over the same period, costs for antidepressant prescribing fell 27.8%. Across all Clinical Commissioning Groups (CCGs) in England, antidepressant prescribing levels, adjusted for population were positively correlated with the index of multiple deprivation (IMD) score. In comparison, prescribing for the top 10 most prescribed cardiovascular medicines increased by 2.75% from 207 million (2015) to 213 million (2019) items. Limitations Anonymised data in the Open-Prescribing Database means no patient diagnoses or treatment plans are linked to this data. Conclusion Antidepressant prescribing, particularly sertraline, is increasing. Prescribing is higher in more deprived regions, but costs are falling to < 2% of all items prescribed. Absolute numbers of prescriptions for cardiovascular medicines are higher, likely reflecting the greater prevalence of cardiovascular disease, and are rising more slowly. This study will enable future work to look at the impact of COVID-19 on prescribing for mental health.

Acrocyanosis and digital necrosis are associated with poor prognosis in COVID-19.

Acrocyanosis and digital necrosis, which caused by microangiopathic and immunothrombosis phenomenon, may accompanied by microvascular involvement of other organs. Therefore, this finding can play a prognostic role in covid-19 outcome.

To stress or not to stress: Brain-behavior-immune interaction may weaken or promote the immune response to SARS-CoV-2.

The COVID-19 pandemic continues to strongly affect people with health disadvantages, creating a heavy burden on medical systems and societies worldwide. Research is growing rapidly and recently revealed that stress-related factors such as socio-economic status, may also play a pivotal role. However, stress research investigating the underlying psychoneuroimmune interactions is missing. Here we address the question whether stress-associated neuroendocrine-immune mechanisms can possibly contribute to an increase in SARS-CoV-2 infections and influence the course of COVID-19 disease. Additionally, we discuss that not all forms of stress (e.g. acute versus chronic) are detrimental and that some types of stress could attenuate infection-risk and -progression. The overall aim of this review is to motivate future research efforts to clarify whether psychosocial interventions have the potential to optimize neuroendocrine-immune responses against respiratory viral infections during and beyond the COVID-19 pandemic. The current state of research on different types of stress is summarized in a comprehensive narrative review to promote a psychoneuroimmune understanding of how stress and its mediators cortisol, (nor)adrenaline, neuropeptides and neurotrophins can shape the immune defense against viral diseases. Based on this understanding, we describe how people with high psychosocial stress can be identified, which behaviors and psychosocial interventions may contribute to optimal stress management, and how psychoneuroimmune knowledge can be used to improve adequate care for COVID-19 and other patients with viral infections.