Lipid-targeting antiviral strategies: current state and future perspectives

Antiviral Research, Journal Year: 2025, Volume and Issue: unknown, P. 106103 - 106103

Published: Feb. 1, 2025

Language: Английский

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Association of fluvoxamine with mortality and symptom resolution among inpatients with COVID-19 in Uganda: a prospective interventional open-label cohort study

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(12), P. 5411 - 5418

Published: March 3, 2023

Abstract Prior research suggests that fluvoxamine, a selective serotonin reuptake inhibitor (SSRI) used for the treatment of obsessive-compulsive disorder and major depressive disorder, could be repurposed against COVID-19. We undertook prospective interventional open-label cohort study to evaluate efficacy tolerability fluvoxamine among inpatients with laboratory-confirmed COVID-19 in Uganda. The main outcome was all-cause mortality. Secondary outcomes were hospital discharge complete symptom resolution. included 316 patients, whom 94 received addition standard care [median age, 60 years (IQR = 37.0); women, 52.2%]. Fluvoxamine use significantly associated reduced mortality [AHR 0.32; 95% CI 0.19–0.53; p < 0.001, NNT 4.46] increased resolution [AOR 2.56; 1.53–5.51; 4.44]. Sensitivity analyses yielded similar results. These effects did not differ by clinical characteristic, including vaccination status. Among 161 survivors, time 0.81, (0.54–1.23), 0.32]. There trend toward greater side (7.45% versus 3.15%; SMD 0.21; χ 2 3.46, 0.06), most which light or mild severity none serious. One hundred mg prescribed twice daily 10 days well tolerated resolution, without significant increase discharge, Large-scale randomized trials are urgently needed confirm these findings, especially low- middle-income countries, where access vaccines approved treatments is limited.

Language: Английский

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Association of severe mental illness and septic shock case fatality rate in patients admitted to the intensive care unit: A national population-based cohort study

PLoS Medicine, Journal Year: 2023, Volume and Issue: 20(3), P. e1004202 - e1004202

Published: March 13, 2023

Background Patients with severe mental illness (SMI) (i.e., schizophrenia, bipolar disorder, or major depressive disorder) have been reported to excess mortality rates from infection compared patients without SMI, but whether SMI is associated higher lower case fatality (CFRs) among infected remains unclear. The primary objective was compare the 90-day CFR in septic shock and admitted intensive care unit (ICU), after adjusting for social disadvantage physical health comorbidity. Methods findings We conducted a nationwide, population-based cohort study of all adult ICU France between January 1, 2014, December 31, 2018, using French national hospital database. matched (within hospitals) ratio 1:up 4 (matched-controls) age (5 years range), sex, degree deprivation, year hospitalization. Cox regression models were adjustment smoking, alcohol other substance addiction, overweight obesity, Charlson comorbidity index, presence trauma, surgical intervention, Simplified Acute Physiology Score II score, organ failures, source admission (home, transfer ward), length time admission. outcome CFR. Secondary outcomes 30- 365-day CFRs, clinical profiles patients. A total 187,587 identified, including 3,812 2,258 5,246 disorder. Compared controls, significantly schizophrenia (1,052/3,269 = 32.2% versus 5,000/10,894 45.5%; adjusted hazard (aHR) 0.70, 95% confidence interval (CI) 0.65,0.75, p < 0.001), disorder (632/1,923 32.9% 2,854/6,303 45.3%; aHR CI 0.63,0.76, (1,834/4,432 41.4% 6,798/14,452 47.1%; 0.85, 0.81,0.90, 0.001). Study limitations include inability capture deaths occurring outside hospital, lack data on processes care, problems missing miscoding medico-administrative databases. Conclusions Our suggest that, comorbidity, there are improved without. This finding may be result different immunological exposures psychotropic medications, which should further explored.

Language: Английский

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Could antidepressants increase mood and immunity at the same time?

Frontiers in Psychiatry, Journal Year: 2025, Volume and Issue: 16

Published: March 12, 2025

A review of scientific literature suggests that the use antidepressants can be broadly extended to address various forms stress and inflammation as an adjunctive therapy enhances host resistance. While effects on mood are well-documented in terms their emotional, cognitive, behavioral impacts, these aspects do not fully explain cellular mechanisms action. At level, exert trophic promote neurogenesis synaptic connectivity. Studies demonstrate improve cell survival, enhance stem proliferation, reduce danger perception (mood effects) depressed patients animal models depression. These properties highlight a deeper biological mechanism beyond mood-related benefits. The acid sphingomyelinase (ASM) theory offers more compelling explanation compared monoamine hypothesis. Antidepressants functionally inhibit ASM enzyme, thereby reducing production ceramide, which directs cells toward increased cytoprotection, reproduction, well improved mood. This also highlights research demonstrating resistance infections, immunological challenges, stress, findings support potential bolster resilience scenarios involving vaccinations, aggression, depression, even aging.

Language: Английский

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Role of Cytochrome P450 2C9 in COVID-19 Treatment: Current Status and Future Directions

European Journal of Drug Metabolism and Pharmacokinetics, Journal Year: 2023, Volume and Issue: 48(3), P. 221 - 240

Published: April 24, 2023

The major human liver drug metabolising cytochrome P450 (CYP) enzymes are downregulated during inflammation and infectious disease state, especially coronavirus 2019 (COVID-19) infection. influx of proinflammatory cytokines, known as a 'cytokine storm', severe COVID-19 leads to the downregulation CYPs triggers new cytokine release, which further dampens CYP expression. Impaired metabolism, along with inevitable co-administration drugs or 'combination therapy' in patients various comorbidities, could cause drug–drug interactions, thus worsening condition. Genetic variability polymorphism CYP2C9 across different ethnicities contribute susceptibility. A number used inducers inhibitors of, metabolised by, CYP2C9, might pharmacokinetic pharmacodynamic interactions. It is also worth mentioning that some interactions due altered activity other including CYP3A4. Isoniazid/rifampin for tuberculosis co-infection; lopinavir/ritonavir cobicistat/remdesivir combination therapy; multi-drug therapy ivermectin, azithromycin, montelukast acetylsalicylic acid, TNR4 therapy, all improved recovery COVID-19. However, inducers, both, plausibly isoforms lead treatment failure, hepatotoxicity serious side effects thromboembolism bleeding, observed combined use azithromycin/warfarin. Further, herbs inhibitors, showed anti-COVID-19 properties, silico predictions postulated phytochemical compounds inhibit SARS-CoV-2 virus particles. vaccines elicit immune responses activate turn suppresses expression be source compromised metabolism subsequent interaction. Future studies recommended determine regulation COVID-19, while recognising involvement possibly utilising target gene tackle ever-mutating SARS-CoV-2.

Language: Английский

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Excess mortality and its causes among older adults with schizophrenia versus those with bipolar disorder and major depressive disorder: a 5-year prospective multicenter study

European Archives of Psychiatry and Clinical Neuroscience, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 31, 2024

Language: Английский

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The IRE1α-XBP1 arm of the unfolded protein response is a host factor activated in SARS-CoV-2 infection

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2024, Volume and Issue: 1870(5), P. 167193 - 167193

Published: April 21, 2024

Language: Английский

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Medications Modulating the Acid Sphingomyelinase/Ceramide System and 28-Day Mortality among Patients with SARS-CoV-2: An Observational Study

Pharmaceuticals, Journal Year: 2023, Volume and Issue: 16(8), P. 1107 - 1107

Published: Aug. 4, 2023

Prior evidence indicates the potential central role of acid sphingomyelinase (ASM)/ceramide system in infection cells with SARS-CoV-2. We conducted a multicenter retrospective observational study including 72,105 adult patients laboratory-confirmed SARS-CoV-2 who were admitted to 36 AP-HP (Assistance Publique-Hôpitaux de Paris) hospitals from 2 May 2020 31 August 2022. examined association between ongoing use medications functionally inhibiting (FIASMA), which reduces vitro, upon hospital admission 28-day all-cause mortality 1:1 ratio matched analytic sample based on clinical characteristics, disease severity and other (N = 9714). The univariate Cox regression model showed that FIASMA medication at was associated significantly lower risks (HR 0.80; 95% CI 0.72-0.88; p < 0.001). In this study, substantially reduced among hospitalized COVID-19. These findings support continuation these during treatment infections. Randomized trials (RCTs) are needed confirm results, starting molecules greatest effect size e.g., fluoxetine, escitalopram, amlodipine.

Language: Английский

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Drug-induced phospholipidosis is not correlated with the inhibition of SARS-CoV-2 - inhibition of SARS-CoV-2 is cell line-specific

Frontiers in Cellular and Infection Microbiology, Journal Year: 2023, Volume and Issue: 13

Published: Aug. 11, 2023

Recently, Tummino et al. reported that 34 compounds, including Chloroquine and Fluoxetine, inhibit SARS-CoV-2 replication by inducing phospholipidosis, although failed to suppress viral in Calu-3 cells patients. In contrast, Fluoxetine represses human precision-cut lung slices (PCLS) cells. Thus, it is unlikely these compounds have similar mechanisms of action. Here, we analysed a subset the phospholipidosis assays using PCLS as patient-near system. Trimipramine induced but cells, which contradicts findings proposed mechanism. only slightly reduced 2.7 orders magnitude. Tilorone suppressed 1.9 magnitude without causing phospholipidosis. induction not correlated with inhibition SARS-CoV-2, act via other mechanisms. However, show such Amiodarone, Tamoxifen Tilorone, antiviral activity on also inhibited PCLS. Our results indicate against are cell-line specific. Data from Vero E6 can lead non-transferable results, underlining importance an appropriate cell system for analysing SARS-CoV-2. We observed correlation between active

Language: Английский

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Genetic analyses point to alterations in immune-related pathways underpinning the association between psychiatric disorders and COVID-19

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: unknown

Published: July 3, 2024

Language: Английский

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