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.

Cryptogenic Stroke In The Context of Pandemic-Related Stress: The Role of Arterial Hemodynamics.

BACKGROUND: Up to 45% of ischemic strokes are cryptogenic, which is an impediment to proposing preventative measures. In this investigation we aimed to study underlying heart arrhythmias in patients with cryptogenic stroke, taking into consideration the context of the COVID-19 pandemic and stressful lockdown conditions. SUBJECTS AND METHODS: In this cross-sectional study we observed 52 patients with cryptogenic stroke >1 month after acute presentation, and a control group consisting of 88 patients without stroke. All patients undewent the laboratory and instrumental investigation consisting of the following: lipid spectrum; hemostasiograms; hemoglobin A1c; transthoracic or/and transesophageal echocardiography; 24-hours monitoring of ECG; computer tomography or magnetic resonance imaging of the brain. We studied the hemodynamics of the common carotid arteries using Doppler ultrasound imaging and digital sphygmography (SG). RESULTS: The groups were indentical with respect to the preponderance of study parameters (sex, age, comorbidities, instrumental and laboratory data). The ischemic stroke group had a statistically significant difference in the prevalence of the first type of extrasystolic arrhythmia according to our gradation of extrasystoles, which are ventricular systoles of extrasystolic contraction appearing before the transmitral blood flow peak (peak E in echocardiography). We observed that earlier ventricular systoles of extrasystole in the cardiac cycle predicted for greater growth of hemodynamic and kinetic parameters. Calculating the indices of a four-field table established the significant relationship between the moment of appearance of extrasystolic ventricular contraction in the cardiac cycle and the risk for cryptogenic stroke (normalized value of the Pearson coefficient (C`) of the two paramaters was 0.318). CONCLUSIONS: Extrasystolic arrhythmia appeared as an additional risk factor of earlier stroke. The most dangerous type of arrhythmia was when the ventricular contraction of the extrasystole appeared before the transmitral blood flow peak in the cardiac cycle. This observation could present a risk-marker for brain-related cardiovascular complications such as stroke, which might be patients suffering from different internal diseases, especially in the context of environmental stress conditions of the current pandemic and its related lockdown measures.

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.

Virtual Reality-Based Interventions for Treating Depression in the Context of COVID-19 Pandemic: Inducing the Proficit in Positive Emotions as a Key Concept of Recovery and a Path Back to Normality.

BACKGROUND: During the COVID-19 pandemic as much as 40% of the global population reported deterioration in depressive mood, whereas 26% experienced increased need for emotional support. At the same time, the availability of on-site psychiatric care declined drastically because of the COVID-19 preventive social restriction measures. To address this shortfall, telepsychiatry assumes a greater role in mental health care services. Among various on-line treatment modalities, immersive virtual reality (VR) environments provide an important resource for adjusting the emotional state in people living with depression. Therefore, we reviewed the literature on VR-based interventions for depression treatment during the COVID-19 pandemic. SUBJECTS AND METHODS: We searched the PubMed and Scopus databases, as well as the Internet, for full-length articles published during the period of 2020-2022 citing a set of following key words: "virtual reality", "depression", "COVID-19", as well as their terminological synonyms and word combinations. The inclusion criteria were: 1) the primary or secondary study objectives included the treatment of depressive states or symptoms; 2) the immersive VR intervention used a head-mounted display (HMD); 3) the article presented clinical study results and/or case reports 4) the study was urged by or took place during the COVID-19-associated lockdown period. RESULTS: Overall, 904 records were retrieved using the search strategy. Remarkably, only three studies and one case report satisfied all the inclusion criteria elaborated for the review. These studies included 155 participants: representatives of healthy population (n=40), a case report of a patient with major depressive disorder (n=1), patients with cognitive impairments (n=25), and COVID-19 patients who had survived from ICU treatment (n=89). The described interventions used immersive VR scenarios, in combination with other treatment techniques, and targeted depression. The most robust effect, which the VR-based approach had demonstrated, was an immediate post-intervention improvement in mood and the reduction of depressive symptoms in healthy population. However, studies showed no significant findings in relation to both short-term effectiveness in treatment of depression and primary prevention of depressive symptoms. Also, safety issues were identified, such as: three participants developed mild adverse events (e.g., headache, "giddiness", and VR misuse behavior), and three cases of discomfort related to wearing a VR device were registered. CONCLUSIONS: There has been a lack of appropriately designed clinical trials of the VR-based interventions for depression since the onset of the COVID-19 pandemic. Moreover, all these studies had substantial limitations due to the imprecise study design, small sample size, and minor safety issues, that did not allow us making meaningful judgments and conclude regarding the efficacy of VR in the treatment of depression, taking into account those investigations we have retrieved upon the inclusion criteria of our particularistic review design. This may call for randomized, prospective studies of the short-term and long-lasting effect of VR modalities in managing negative affectivity (sadness, anxiety, anhedonia, self-guilt, ignorance) and inducing positive affectivity (feeling of happiness, joy, motivation, self-confidence, viability) in patients suffering from clinical depression.

Association between COVID-19 and catatonia manifestation in two adolescents in Central Asia: Incidental findings or cause for alarm?

Catatonia is a rare neuropsychiatric syndrome that can accompany various medical conditions, including schizophrenia, autoimmune encephalitis, and infectious diseases. We present two cases of catatonia in males aged 12 and 17 years from Central Asia who tested positive for SARS-Cov-2 antibodies. Detailed medical assessments declined other potential precipitating factors, including schizophrenia or anti-NMDA receptor autoimmune encephalitis. FDG-PET in the younger patient demonstrated focal hypometabolism in left frontotemporal and right associative visual cortex, matching patterns previously seen in adults with catatonia. These isolated findings raise concerns about a possible causal relationship between COVID-19 infection and risk of catatonia manifestation in adolescents.

A comprehensive review of imaging findings in COVID-19 - status in early 2021.

Medical imaging methods are assuming a greater role in the workup of patients with COVID-19, mainly in relation to the primary manifestation of pulmonary disease and the tissue distribution of the angiotensin-converting-enzyme 2 (ACE 2) receptor. However, the field is so new that no consensus view has emerged guiding clinical decisions to employ imaging procedures such as radiography, computer tomography (CT), positron emission tomography (PET), and magnetic resonance imaging, and in what measure the risk of exposure of staff to possible infection could be justified by the knowledge gained. The insensitivity of current RT-PCR methods for positive diagnosis is part of the rationale for resorting to imaging procedures. While CT is more sensitive than genetic testing in hospitalized patients, positive findings of ground glass opacities depend on the disease stage. There is sparse reporting on PET/CT with [18F]-FDG in COVID-19, but available results are congruent with the earlier literature on viral pneumonias. There is a high incidence of cerebral findings in COVID-19, and likewise evidence of gastrointestinal involvement. Artificial intelligence, notably machine learning is emerging as an effective method for diagnostic image analysis, with performance in the discriminative diagnosis of diagnosis of COVID-19 pneumonia comparable to that of human practitioners.