Assessing the effect of selective serotonin reuptake inhibitors in the prevention of post-acute sequelae of COVID-19

Computational and Structural Biotechnology Journal, Journal Year: 2024, Volume and Issue: 24, P. 115 - 125

Published: Jan. 9, 2024

BackgroundPost-acute sequelae of COVID-19 (PASC) produce significant morbidity, prompting evaluation interventions that might lower risk. Selective serotonin reuptake inhibitors (SSRIs) potentially could modulate risk PASC via their central, hypothesized immunomodulatory, and/or antiplatelet properties although clinical trial data are lacking.Materials and MethodsThis retrospective study was conducted leveraging real-world within the National COVID Cohort Collaborative (N3C) to evaluate whether SSRIs with agonist activity at sigma-1 receptor (S1R) PASC, since agonism this may serve as a mechanism by which attenuate an inflammatory response. Additionally, determine potential benefit be traced S1R agonism. Presumed defined based on computable phenotype trained U09.9 ICD-10 diagnosis code.ResultsOf 17,908 patients identified, 1521 were exposed baseline SSRI, 1803 non-S1R 14,584 neither. Using inverse probability weighting Poisson regression, relative (RR) assessed.A 29% reduction in RR (0.704 [95% CI, 0.58-0.85]; P = 4 ×10-4) seen among who received SSRI compared unexposed 21% those receiving without (0.79 0.67 - 0.93]; 0.005).Thus, reported associated decrease PASC.

Language: Английский

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Prevalence and Determinants of Long-term Post-COVID Conditions in the United States: 2022 Behavioral Risk Factor Surveillance System

The American Journal of Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 1, 2024

Language: Английский

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Long-COVID-19 autonomic dysfunction: An integrated view in the framework of inflammaging

Mechanisms of Ageing and Development, Journal Year: 2024, Volume and Issue: 218, P. 111915 - 111915

Published: Feb. 13, 2024

Language: Английский

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SSRI Use During Acute COVID-19 Infection Associated with Lower Risk of Long COVID Among Patients with Depression

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Feb. 6, 2024

ABSTRACT Background Long COVID, also known as post-acute sequelae of COVID-19 (PASC), is a poorly understood condition with symptoms across range biological domains that often have debilitating consequences. Some recently suggested lingering SARS-CoV-2 virus in the gut may impede serotonin production and low drive many COVID systems. Therefore, selective reuptake inhibitors (SSRIs), which increase synaptic availability, prevent or treat COVID. SSRIs are commonly prescribed for depression, therefore restricting study sample to only include patients depression can reduce concern confounding by indication. Methods In an observational electronic health records from National Cohort Collaborative (N3C) diagnosis between September 1, 2021, December 2022, pre-existing major depressive disorder, leading indication SSRI use, we evaluated relationship use at time infection subsequent 12-month risk (defined ICD-10 code U09.9). We defined prescription medication beginning least 30 days before not ending infection. To minimize bias, estimated causal associations interest using nonparametric approach, targeted maximum likelihood estimation, aggressively adjust high-dimensional covariates. Results analyzed ( n = 506,903) disorder diagnosis, where 124,928 (25%) were SSRI. found users had significantly lower compared nonusers (adjusted relative 0.90, 95% CI (0.86, 0.94)). Conclusion These findings suggest during be protective against supporting hypothesis key mechanistic biomarker

Language: Английский

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Gastrointestinal manifestations of long COVID

Life Sciences, Journal Year: 2024, Volume and Issue: unknown, P. 123100 - 123100

Published: Sept. 1, 2024

Language: Английский

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Post-infectious irritable bowel syndrome: Focus on serotonin metabolism disturbances and gut microbiota modulation

Medical alphabet, Journal Year: 2025, Volume and Issue: 34, P. 36 - 41

Published: Jan. 24, 2025

Post-infectious irritable bowel syndrome (PI–IBS) is the first phenotype of disease described in literature and most studied to date. The prevalence PI–IBS population continues grow steadily especially post-COVID-19 pandemic period. Taking into account accumulated scientific clinical data dysfunction functional axis «microbiota-gut-brain» associated with formation visceral hypersensitivity intestinal motor disorders due abnormal serotonin metabolism, increased permeability low-grade inflammation considered as a key pathogenetic factor underlying development persistence symptoms. This review article analyzes summarizes information on mechanisms changes neurohumoral regulation, well qualitative quantitative composition microbiota. In addition, possibility using probiotic therapy complex patients are presented.

Language: Английский

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Serotonergic psychedelics as potential therapeutics for post-COVID-19 syndrome (or Long COVID): A comprehensive review

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2025, Volume and Issue: unknown, P. 111279 - 111279

Published: Feb. 1, 2025

Language: Английский

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Disruptions in serotonin- and kynurenine pathway metabolism in post-COVID: biomarkers and treatment

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

Published: Feb. 13, 2025

This opinion article attempts to connect knowledge about post-Covid syndrome (PCS) gained in neuropsychiatry and immunology. It discusses some misunderstandings PCS light of the interplay between serotonergic system kynurenine pathway (KP). From a new perspective, potential biomarkers for further research therapeutic targets are identified.Due severity extent PCS, researchers urgently searching its causes treatments. For neurocognitive autonomic nervous problems such as present it is common encounter dysregulated neurotransmitter systems. Among neurotransmitters, serotonin plays special role immune regulating inflammatory responses by central peripheral mechanisms (1)(2)(3)(4)(5). Serotonin -also known 5-hydroxytryptamine (5-HT) -is with stimulating effect that influences memory, mood, selfconfidence, sleep, emotion, orgasm eating (6)(7)(8)(9).Serotonin not only binds receptors on neurons, but also cells (3,5,10,11). Many studies have indicate receptors, especially 5-HT3 (one receptors), involved pathogenesis chronic conditions (5,10,11). Therapeutic applications receptor antagonists instance been reported rheumatoid arthritis (5,11,12). An essential amino acid KP tryptophan, precursor both (see figure1), we get through food part regular diet (13). The creating an important energy factor modulated infection stress (1,5)and subsets T helper 17 (Th17 cells) produce cytokines signaling function (14).Strong alterations intestinal gene expression upregulate genes viral recognition inflammation pathways downregulate nutrient metabolism, like tryptophan (15). downregulation result serum reduction Various suspect this might be cause complaints (15)(16)(17)(18)(19).In I address question whether disruptions serotonin-and metabolism lead treatment PCS.In study 'Serotonin post-acute sequelae infection' Wong et al. (15) they investigated four human cohorts, animal models organoid cultures. First, conducted among 1540 patients who presented center severe complaints. They identified eight clusters based clinical symptoms, varying from mainly physical problems, loss strength muscles, memory disorders. performed targeted plasma metabolomics 58 representative 3-22 months after found compared 30 healthy controls.For finding three causes: a) diminished absorption tryptophan. Because angiotensin converting enzyme (ACE2) these strongly decreased. Furthermore, COVID-19 virus spike proteins attaches (20,21). As consequence, during infection, has compete over reduced number ACE2 receptors; b) micro-clots thrombocytes. Thrombocytes contain serotonin. reduce thrombocytes thus availability serotonin; c) enhanced monoamine oxidase (MAO) promotes breakdown serotonin.In Sadlier (17), cohort 20 hospitalized were controls, 4-6 6-9 infection. Levels multiple metabolites immunomodulatory properties elevated quinolinate, toxic metabolite. There levels other things glutamate (a neurotransmitter) level was increased.Su (18) longitudinal multi-omic analysis (n=209). followed immediately Covid-19 had less symptoms. measured autoantibodies, specific RNAemia, metabolic profiles, global proteomic blood mononuclear (PBMCs) draws. no 457 controls. What striking stands out reporting neurological symptoms exhibited associated negative regulation circadian sleep/wake cycle. hormone melatonin responsible produced brain (in pineal gland) serotonin.Wong conclude serious greater chance permanently retaining than mild checked Peluso (22) did indeed negatively correlate complaints.However, retrospective Mathé (19) using Liquid Chromatography -Mass Spectrometry (lc-ms/ms) technology 34 at least 6 complaints, which 14 controls.Although colleagues much more extensive most comprehensive all interesting results, agree conclusion reliable biomarker should used routine diagnostic assessment, two arguments.The first reason cannot cross blood-brain barrier appears reaches via cranial nerve, vagus nerve normally uses Acetylcholine (Ach) (9). So, directly related brain. Based models, assume PCS. In vivo, however, technically very difficult measure With possible techniques (microdialysis, functional magnetic resonance imaging (fMRI), fast-scan cyclic voltammetry (FSCV), genetically encoded indicators (GESIs) positron emission tomography (PET) either spatiotemporal resolution too poor or technique invasive or/and expensive .However, vivo you (23). authorsWong can move up hippocampus, control causing disorders our describe into 95 selective reuptake inhibitors (SSRIs) 'Treatment SSRIs' ( 16), give however another explanation. We hypothesize occurs brainstem After all, pons origin serotoninergic there, axons sent throughout (CNS) (6,7). afferent arises (6,7) full attach (20). Hypometabolic areas (24,25).Further corroboration argument rRecent Besteher (26) confirms argument. fMRI scans suffering neuropsychiatric (n = 30) significantly larger gray matter volumes (GMV) controls 20). Such example prefrontal cortex (PFC) -which range higher order cognitive functions limbic (27). predominates (27,28). authors state enlargement GMV could sign recovery neurogenesis compensation (26). However, Another explanation cerebral swelling caused reactions.Using PET -for transmission systems -researchers see exactly what happening enlarged Given persist, seems likely pathology. Moreover, provides plausible positive SSRIs when there something wrong balance those regions (16).Furthermore, Su melatonin, serotonin, reduced. additional support-contrary -that may reduced.The second reject biomarker, variability degree variable cohorts different (15,(17)(18)(19). probably many variables studies. as: time passed measurement: ranging 0 22 months, their exact quantification (especially subjective complaints) subgroups belonged cohort. believe methodology therefore results vary research.Unlike (9,13) better option (14,16). expected if instead levels, case comparative above preferably comparable.Beside given colleagues, fourth cause: KP, create nicotinamide adenine dinucleotide (NAD+), interacts extensively system, activated (14,(29)(30)(31). formation process demands lot 14) figure1) because deficiency (9).In study, decline lasted longer. Therefore, major reduction. Guo (30) show persistently INDO-2, stimulates production (figure 1). Cron (14) (such quinoline), while depleted. Additionally, Cysique significant relationship impairment (29). These overactivity KP. active left Figure 1 2.4. overactive deficiencies hormones neurotransmitters illustrates too. regulates cycle (17,32). sleep (16,33).Too due runaway feedback loop blocks tetrahydrobiopterin (BH4), coenzyme dopamine, turn ensures (nor)epinephrine Norepinephrine sympathetic increases frequency force muscle contractions (34)why symptom SNRI (selective norepinephrine inhibitor) SSRI (16).If look metabolites, quinolinic glutaminergic antagonists. accumulation (35) leads various concentration palpitations (35), often suffer (16,33). That why recommend (16) Nacetylcysteine drug restore (35). (36). stimulatesexcept besides pathological propose would preferable choose 5-hydroxytryptophan (5-HTP, confused 5-HT)5hydroxytryptophan) 5-HTP direct does feed barrier. 2.5.2. reduces -to lesser -norepinephrine presynaptic neuron allows synapse transmit signal postsynaptic longer period Normally usually described depression anxiety (37).Wong mice treated fluoxetine (an SSRI) improved Previously, several took SSRIs, lower developing (38)(39)(40)(41)(42)(43).In exploratory thirds PCS-patients showed considerable even strong being (16). confirmed hypothesis regarding importance formulated seven action one hypothetical mechanism. short: , short. instance, a. influence hypothalamic -pituitary -adrenalaxis (HPA-axis, system) (44-51), b. circulatory (52,53), c. . Bby prolonging clotting theoretically help dissolve microclots (54), d. oxidative e. tThe fluvoxamine shown extra anti-inflammatory effects inhibiting sphingomyelinase (ASM) (55), f. pro-inflammatory interleukin 2 (IL 2) IL CNS (56) -in achieve effects, must then sigma1 agonist receptor) (56),. g. stimulate hippocampus (9,57). Finally, slow down (9).Disruptions -and provide clear direction advancing line inquiry. literature noticed While evident scientists explore focus route (14,(29)(30)(31) (15,(17)(18)(19)36), typically overlook possibility routes related, regard pathology overlooked.Additionally, sSerotonin assessment turned (15,(17)(18)(19)22). Tryptophan option. comparable.Toxic good well, (29).Wong advised do examine (15)(16)(17)36). A randomized controlled trial (RCT) follow under strict conditions, testing pharmacogenetic profile advance, since absorb break quickly slowly lack desired side effects. excluded RCT outside context RCT. sensitive stop increasing dosage threatens tip without affecting requirements RCT.Furthermore recommended Therefore option.This review call collaboration immunologists, neurologists psychiatrists field neuroimmunology. already examples psychiatric diseases immunologically, schizophrenia (58)(59)(60)(61)(62), childhood (61,63,64) still unravel neuroimmunology immunological psychotropic drugs considered. (KP) same building block system. From: Treatment

Language: Английский

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Objectifying persistent subjective cognitive impairment following COVID-19 infection: cross-sectional data from an outpatient memory-clinic in Germany

European Archives of Psychiatry and Clinical Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 28, 2025

Abstract Objective Subjective cognitive impairment is frequently reported by patients experiencing Post-COVID symptoms. This study aims to assess objective in attention, memory, and executive functions among these patients. Further, we investigated potential determinants of impairment. Methods In this cross-sectional study, standardized neuropsychological testing (Vienna Testing System), assessment symptom aggravation, psychiatric anamnesis, psychometrics (BDI-II, Fatigue Severity Scale) were conducted 229 who voluntarily presented our outpatient memory-clinic due subjective following COVID-19. Blood-samples collected peripheral immune markers (IL-6, CRP) APOE-ε4 genotype. Results at least one domain was present 39% the 47% showed symptoms moderate or severe depression. The APOE -ε4 allele 32% Higher rates depressive (OR = 1.41, 95%-CI 1.02–1.95) higher burden 3.29, 1.51–7.40) predicted impairment, regardless age, sex, years formal education, time since infection, medication for diabetes hypertension. severity, acute COVID-19 severity inflammation had no impact. Conclusions more likely associated with high depression rather than relatively low performance. Thus, emphasizes necessity extensive evaluation when examining clinical practice. link between does not appear be specific Therefore, depression- APOE-ε4-mediated neurodegenerative pathomechanisms might a promising therapeutical target.

Language: Английский

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Neuropsychiatric Manifestations of Long COVID-19: A Narrative Review of Clinical Aspects and Therapeutic Approaches

Life, Journal Year: 2025, Volume and Issue: 15(3), P. 439 - 439

Published: March 11, 2025

The COVID-19 (C-19) pandemic has highlighted the significance of understanding long-term effects this disease on quality life those infected. Long (L-C19) presents as persistent symptoms that continue beyond main illness period, usually lasting weeks to years. One lesser-known but significant aspects L-C19 is its impact neuropsychiatric manifestations, which can have a profound effect an individual’s life. Research shows creates issues such mental fog, emotional problems, and brain symptoms, along with sleep changes, extreme fatigue, severe head pain, tremors seizures, pain in nerves. People cognitive problems plus fatigue mood disorders experience great difficulty handling everyday activities, personal hygiene, social interactions. Neuropsychiatric make people withdraw from activity hurt relationships, thus causing feelings loneliness. unpredictable state generates heavy psychological pressure through suffering, including depression anxiety. changes impairment, swings it hard for work or study effectively, decreases their output at school lowers job contentment. purpose narrative review summarize clinical data present literature regarding manifestations L-C19, identify current methods diagnosis treatment lead correct management condition, highlight these patients’

Language: Английский

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