Depression and Anxiety Among COVID-19 Patients Admitted to a "Red Zone" Intensive Care Unit: Do the Factors of Self-Awareness of Somatic Health, Anxiety, and Depression Contribute to the Course of Sars-Cov-2 Infection?

BACKGROUND: The prevalence of depressive disorders in the general population increased significantly during the COVID-19 pandemic. The aim of this study is to examine the relationship between history of anxiety and depressive disorders and COVID-19 outcome, hospitalization and severity of anxiety and depression, and whether such relationships are explicable by direct impact of the disease. SUBJECTS AND METHODS: We conducted a questionnaire survey among 98 inpatients in the Department of Infectious Diseases of the Clinics of Samara State Medical University. The self-report questionnaire consisted of 120 items, including socio-demographic characteristics of participants, State-Trait Anxiety Inventory, and the Center for Epidemiologic Studies Depression Scale, with items reflecting subjective feelings about the COVID-19 pandemic. We used one-factor analysis of variance to compare between groups for those indicators that conformed to a normal distribution, and the chi-square test (χ2) or Fisher's exact test to analyze group differences in the distribution of categorical variables was used. RESULTS: The mean (SD) total score on the STAI anxiety scale among hospitalized patients (51 (10.1)) significantly exceeded that of the COMET-G control group (44.9 (11.7) (H=22.8, p<0.001). There was a similar difference in the severity of depression as measured by the CES-D scale (23.4 (12.6) versus 18.0 (11.8), H=15.2 and p<0.001). In contrast to the general population, there were no statistically significant differences in anxiety and depression severity in the matched samples 52 subjects fulfilling the criteria of age, gender, and general perception of health condition. CONCLUSIONS: Anxiety and depression scores among ICU (red zone) inpatients significantly exceeded the scores observed in the COMET-G general population group. Our study did not confirm expected relationship between symptoms of anxiety and depression (based on questionnaire response) and the risk of severe course of COVID-19 (e.g. hospitalization) in matched samples, but proved that the factor of self-awareness of health state may be related to the COVID-19 course severity. Future research would benefit from clinical interview of inpatients and follow-up monitoring of affective disorders to specify whether anxiety and particular type of depression (e.g., anxious) are selectively related to the severity of COVID-19 course and risks of affective disorders persistence after somatic recovery. The accumulation of mental disorders with age, and the bidirectional association of mood disorders and infectious diseases should be considered when assessing the risk factors.

Perceived Psychological Well-Being in Patients with Hemodynamically Insignificant Carotid Arteries Stenosis.

BACKGROUND: Analysis of the perception of the disease in borderline stenosis of the orifice of the internal carotid artery (ICA) (up to 69% in diameter) in asymptomatic patients. SUBJECTS AND METHODS: 48 patients (28 men and 20 women). Group 1: stenosis up to 49% - 23 people (13 men, 10 women), mean age 50.4±16.1 y.o. Group 2: stenosis 50-59% - 18 people (10 men, 8 women), mean age 57.3±16 y.o. Group 3: stenosis 60-69% - 7 people (5 men, 2 women), mean age 61±12.3 y.o. All patients underwent ultrasound Doppler of brachiocephalic arteries, examination with Brief Illness Perception Questionnaire E. Broadbent (Russian version). RESULTS: According to the results of examination of patients with ICA stenosis, patients with more pronounced lesions (60-69%) more often have a type of reaction "negative attitude to the consequences of the disease". CONCLUSIONS: The majority of patients (54.2%) have a "negative type of attitude towards the consequences of the disease". This type of attitude to the disease is most pronounced in women and patients with stenosis of the ICA 60-69%. It is necessary to perform the psychological work with patients with carotid stenosis in order to form in them more adaptive types of perception of the disease, understanding of the disease and a positive attitude towards treatment.

Pharmacogenetic Aspects of COVID-19 Management and Post-COVID-19 Depression Treatment with Fluvoxamine.

BACKGROUND: Quarantine measures with self-isolation of varying duration have been significant psychosocial stressors in the context of the COVID-19 pandemic. The serotonin selective reuptake inhibitor fluvoxamine has been considered as a prophylaxis against depression in early COVID-19 patients, with additional benefits apparently arising from its antiviral activity. In this narrative review, we draw attention to the body of evidence showing efficacy of fluvoxamine in protecting against depressive disorders in COVID-19 patients, while also attenuating the severity of COVID-19 disease, with a notable reduction in the need for intubation and lower mortality. We consider this potential two-fold action of fluvoxamine in the light of its pharmacogenetic and pharmacological profiles. SUBJECTS AND METHODS: Full-text publications in English and Russian in Google Scholar, PubMed, NCBI, Web of Science, and E-Library databases were selected by keywords, solitary and in combination (fluvoxamine, COVID-19, depression, anxiety, antidepressants, adverse reactions) for the period from March 01, 2020 to June 06, 2022. We also analyzed the full-text publications in English and Russian language reporting adverse reactions caused by fluvoxamine use for the period from 2012 to 2022. RESULTS: The literature search yielded 10 papers reporting on the efficacy fluvoxamine in relieving depressive symptoms in COVID-19 patients, and 3 papers on its effect on medical outcome. The preponderance of data indicated a dual therapeutic action of fluvoxamine, and our further literature investigation was informative about drug-drug interactions and genetic factors moderating the antidepressant efficacy of fluvoxamine. CONCLUSIONS: Patients with COVID-19 seeking psychopharmacological treatment for depressive symptoms must be informed of the benefits and risks of fluvoxamine use. Several lines of findings indicate this agent to possess an additional antiviral action. However, optimal dosage regimens and the trade-off with drug-drug interactions remain unclear. Pharmacogenetic testing may assist in evidence-based optimization of fluvoxamine dosages in the context of COVID-19 infection with comorbid depression.

Possible Clinical and Pharmacogenetic Predictors of the Efficacy and Safety of Carbamazepine in Post-COVID-19 Depression.

BACKGROUND: Individuals who have suffered from novel coronavirus disease (COVID-19) are at risk for developing post-COVID neuropsychiatric disorders, which are an integral part of the Long COVID syndrome. Depression and/or anxiety are considered the most common psychiatric disorders after experiencing COVID-19. Certain antiepileptic drugs, notably, carbamazepine (CMZ), are effective in the treatment of mood disorders, especially as mood stabilizers in bipolar affective disorder (BAD), but the efficacy of CMZ in Long COVID remains to be established. The aim of the review was to investigate pharmacogenetic predictors of safety and efficacy of CMZ in patients with depressive symptoms of Long COVID during the post-infection period. SUBJECTS AND METHODS: We carried out a systematic search for publications in English and Russian on the safety and efficacy of CMZ in depressive disorders of different etiologies in the PubMed, Web of Science, Springer, Clinical Keys, Google Schooler, E-Library databases using keywords and combined word searches (carbamazepine, COVID-19, depression, epilepsy, post-COVID-syndrome) for the period from January 01,2020 to June 10, 2022. RESULTS: We review the main adverse drug reactions (ADRs) associated with CMZ, drug-drug interactions, and genetic predictors of the development of ADR. Here, we consider as risk factors, candidate genes for CMZ metabolism, CMZ transport, immunohistocompatibility genes, and candidate genes for QT prolongation. CONCLUSIONS: The choice of antidepressant treatment for patients with Long COVID is fraught because of the frequent occurrence of subclinical (interictal) epileptiform activity in the EEG. Consequently, antidepressant medications with a proconvulsant effect are contraindicated for Long COVID patients. CMZ may be a promising alternative for the treatment of depressive disorders in Long COVID states, given its mood-stabilizer, antidepressant, and antiepileptic profile.

Randomized multicenter noninferiority phase III clinical trial of the first biosimilar of eculizumab.

Currently, eculizumab is the main effective treatment for paroxysmal nocturnal hemoglobinuria (PNH). The aim of this randomized multicenter noninferiority study was to evaluate the efficacy and safety of the Biosimilar (Elizaria) in comparison with the Originator (Soliris) in patients with PNH. Biosimilar and Originator were administered at a dose of 600 mg weekly for 4 weeks at the initial stage in naive patients, as well as for maintenance therapy at a dose of 900 mg every 2 weeks in all patients. The primary endpoint was a comparative assessment of hemolytic activity based on the area under the lactate dehydrogenase (LDH) concentration-time curve during the maintenance therapy. Thirty-two (32) patients were randomized for therapy with Biosimilar (n = 16) or Originator (n = 16). The mean values of LDH concentration-time curve were similar in both treatment groups without statistically significant differences (p > 0.05). Evaluation of secondary endpoints has shown no statistically significant differences between the groups. Safety values were comparable in both treatment groups. The data obtained confirm that the Biosimilar is not inferior to the Originator in terms of the main efficacy parameter, and is also comparable with it in terms of safety and additional efficacy parameters. Clinicaltrials.gov identifier: NCT04463056.

Comprehensive Analysis of Factors Associated with New Episode of Postoperative Atrial Fibrillation after Coronary Artery Bypass Graft Surgery.

The aim of the study was to perform a comprehensive fundamental analysis of the factors of inflammation, oxidative stress, fibrosis, myocardial dysfunction, ischemia and omega-3 index associated with postoperative atrial fibrillation (POAF) after coronary artery bypass graft (CABG) surgery in patients with coronary artery disease. The study involved 158 patients who were admitted to the hospital to undergo CABG surgery. Patients were divided into two groups: group 1 comprised 111 patients without POAF (82% males, median age-62.0 (56.0; 66.0) years), and group 2 comprised 47 patients with POAF (84.4% males, median age-65.0 (61.0; 70.0) years). POAF occurred 5.2 (2.0; 7.0) days after CABG. In all the patients, we evaluated laboratory tests before and 3-4 days after CABG. All the patients also underwent echocardiography. According to results of multifactorial regression analysis, the odds ratio of POAF development for left atrial diameter >41 mm was 4.3 (95% confidence interval (CI) 2.0-9.7, p < 0.001), interleukin (IL)-6 postoperative levels >22.07 pg/mL-3.0 (95% CI 1.4-8.2, p = 0.006), IL-8 postoperative levels >9.67 pg/mL-2.3 (95% CI 1.2-7.3, p = 0.006), superoxide dismutase postoperative levels in plasma >1100.5 U/g-3.2 (95% CI 1.4-9.2, p = 0.03), glutathione postoperative levels ≤0.194 micromole/g of hemoglobin-1.9 (95% CI 1.2-6.3, p < 0.001), glutathione peroxidase postoperative levels ≤17.36 millimole/g of hemoglobin-2.2 (95% CI 1.1-8.2, p < 0.001), glutathione reductase postoperative levels ≤2.99 millimole/g of hemoglobin-2.3 (95% CI, 1.1-5.7, p < 0.001), malondialdehyde postoperative levels >1.25 micromole/g of hemoglobin-2.0 (95% CI, 1.2-7.9, p < 0.001), NO postoperative levels in plasma >36.4 micromole/L-1.5 (95% CI, 1.1-5.9, p < 0.001) and omega-3 index ≤1.59%-2.6 (95% CI 1.5-9.1, p < 0.001). Our study showed that increased left atrial diameter, high postoperative levels of inflammatory factors, oxidative stress, fibrosis indicators and omega-3 index were associated with POAF in patients who underwent CABG.

Biosimilar erythropoietin in anemia treatment (BEAT)-Efficacy and safety of a 1:1 dose conversion from EPREX® to EPIAO® in patients with end-stage renal disease on hemodialysis: A prospective, randomized, double blind, parallel group study.

BACKGROUND: EPREX®/ERYPO®/PROCRIT® (epoetin alfa, Janssen-Cilag GmbH) was the first available recombinant human erythropoietin (rHuEPO) and was universally reference product as per the recommendation provided by European Medicines Agency. EPIAO® is a biosimilar formulation of EPREX®, and making it a 1:1 dose conversion from EPREX® according to recommendation of European Medicines Agency. This study evaluated the clinical efficacy and safety of EPIAO® in subjects with end-stage renal disease receiving hemodialysis after intravenous administration. METHODS: This study was a multicenter, prospective, randomized, double-blind, parallel-group, 2-cohort, maintenance phase, therapeutic equivalence study to evaluate a 1:1 dose conversion from EPREX® to EPIAO® in terms of clinical efficacy and safety that was conducted at 20 sites in 2 countries in patients with end-stage renal disease on hemodialysis. Eligible subjects were treated with EPREX® (reference product of epoetin) for a period of at least 3 months before the treatment period, and then were randomly assigned to the group of EPREX® or EPIAO®. Primary endpoints were mean absolute change in hemoglobin level and mean absolute change in weekly epoetin dosage from baseline to 6 months after treatment with EPIAO®/EPREX® in parallel groups. RESULTS: A total of 200 people received the random intervention and were included in the safety set. After 6, 9, and 12 months of treatment with EPIAO® or EPREX®, there were no significant differences in the hemoglobin levels of the 2 groups compared with baseline. The 95% confidence interval for the treatment difference was within the predetermined acceptable range: ±0.5 g/dL. There were no significant differences in the epoetin dosage of the 2 groups compared with the baseline. The 95% confidence interval for the treatment difference was within the predetermined acceptable range: ± 45 IU/kg. There were no significant differences in the incidence of adverse events between the EPIAO® and EPREX® groups. Most adverse events were mild to moderate and were reverted/resolved. CONCLUSION: EPIAO® demonstrated promising effectiveness and manageable safety in patients with end-stage renal disease on hemodialysis.