A Molecular Biomarker-Based Triage Approach for Targeted Treatment of Post-COVID-19 Syndrome Patients with Persistent Neurological or Neuropsychiatric Symptoms.

Approximately 30% of COVID-19 cases may experience chronic symptoms, known as post-COVID-19 syndrome (PCS). Common PCS symptoms can include fatigue, cognitive impairment, and persistent physical, neurological, and neuropsychiatric complaints. To improve healthcare and management of the current and future pandemics, we highlight the need for establishing interdisciplinary post-viral outpatient clinics comprised of specialists in fields such as psychiatry, psychotherapy, neurology, cardiology, pneumology, and immunology. In this way, PCS patients with a high health burden can receive modern diagnostics and targeted therapeutic recommendations. A key objective is to distinguish the "sick recovered" from the "healthy recovered." Our hypothesis is that there is a PCS subgroup with autoimmune-mediated systemic and brain-vascular dysregulation, which may lead to circulatory disorders, fatigue, cognitive impairment, depression, and anxiety. This can be clarified using a combination of specific antibody diagnostics and precise clinical, psychological, and apparative testing.

Changes in leukocytes and CRP in different stages of major depression.

BACKGROUND: We recently reported increased levels of neutrophils, monocytes and C-reactive protein (CRP) correlated with symptom severity in acute schizophrenia. Here, we investigated if a similar pattern of innate immune system activation occurs in major depression (MD). METHODS: We assessed differential blood counts, CRP, depression symptoms (HAMD-21) and psychosocial functioning (GAF) in controls (n = 129) and patients with first (FEMD: n = 82) or recurrent (RMD: n = 47) disease episodes of MD at baseline (T0; hospital admission) and after 6-weeks treatment (T6). RESULTS: Considering smoking, BMI and gender as covariates, neutrophils (FEMD: p = 0.034, RMD: p = 0.034) and CRP (FEMD: p < 0.001, RMD: p = 0.021) were higher, and eosinophils (FEMD: p = 0.005, RMD: p = 0.004) lower in patients versus controls at T0. Baseline lymphocyte counts were elevated in RMD (p = 0.003) but not FEMD. Results were confirmed by analyses of nonsmokers. At follow-up, eosinophils rose significantly in FEMD (p = 0.011) but no significant changes were observed in RMD. Improvement in HAMD-21 correlated with T0-T6 changes of neutrophil counts in FEMD (r = 0.364, p = 0.024). Compared with our previous schizophrenia study, raised baseline neutrophil and reduced eosinophil counts in MD had smaller effect sizes and treatment had a weaker association with T0-T6 changes in neutrophils. In addition, lymphocytes were elevated at T0 in recurrent MD but not in schizophrenia patients. CONCLUSIONS: These findings suggest that innate immunity may be involved in early stages of MD, and adaptive immunity may be involved in chronic disease. Thus, further studies may lead to new disease stage-dependent MD treatment strategies targeting different aspects of immune system activation.

Molecular mimicry of NMDA receptors may contribute to neuropsychiatric symptoms in severe COVID-19 cases.

Approximately 30% of individuals with severe SARS-CoV-2 infections also develop neurological and psychiatric complaints. In rare cases, the occurrence of autoimmune encephalitis has been reported after SARS-CoV-2 infection. In this systematic review, we have identified eight SARS-CoV-2-associated cases of anti-NMDA receptor encephalitis. All had cerebrospinal fluid antibodies against the NMDA receptor and a recent onset of working memory deficits, altered mental status, or psychiatric symptoms, such as confusion, agitation, auditory hallucination, catatonia and speech dysfunction. All patients received high-dose steroid and immunoglobulin therapeutics and conditions improved in each case. These findings suggest that clinical attention should be paid to warning signs of autoimmune encephalitis in severe COVID-19 cases. If characteristic features of autoimmune encephalitis are present, autoantibody diagnostics should be performed and confirmed cases should be treated with immunotherapy to minimize neurological impairments.

Reduced habenular volumes and neuron numbers in male heroin addicts: a post-mortem study.

The Habenula is increasingly being investigated in addiction. Reduced volumes of other relevant brain regions in addiction, such as nucleus accumbens, globus pallidus and hypothalamus have been reported. Reduced volumes of the habenula as well as reduced neuronal cell count in the habenula have also been reported in mood disorders and an overlap between mood disorders and addiction is clinically widely recognized. Thus, our aim was to investigate possible volume and neuronal cell count differences in heroin addicts compared to healthy controls. Volumes of the medial (MHB) and lateral habenula (LHB) in heroin addicts (n = 12) and healthy controls (n = 12) were assessed by morphometry of 20 µm serial whole brain sections. Total brain volume was larger in the heroin group (mean 1466.6 ± 58.5 cm3 vs. mean 1331.5 ± 98.8 cm3), possibly because the heroin group was about 15 years younger (p = 0.001). Despite larger mean whole brain volume, the mean relative volume of the MHB was smaller than in healthy non-addicted controls (6.94 ± 2.38 × 10-6 vs.10.64 ± 3.22 × 10-6; p = 0.004). A similar finding was observed regarding relative volumes of the LHB (46.62 ± 10.90 × 10-6 vs. 63.05 ± 16.42 × 10-6 p = 0.009). In parallel, neuronal cell numbers were reduced in the MHB of heroin-addicted subjects (395,966 ± 184,178 vs. 644,149 ± 131,140; p < 0.001). These findings were not significantly confounded by age and duration of autolysis. Our results provide further evidence for brain-structural deficits in heroin addiction.

Possible temporal relationship between SARS-CoV-2 infection and anti-NMDA receptor encephalitis: a meta-analysis.

The global impact of SARS-CoV-2 infection has raised concerns about secondary diseases beyond acute illness. This review explores the significance and potential underlying mechanisms of how SARS-CoV-2 infection might elicit an immune response targeting N-methyl-D-aspartate (NMDA) receptors, and its implications for autoimmune-driven neuropsychiatric manifestations. We identified 19 published case reports of NMDA receptor encephalitis associated with SARS-CoV-2 infection or vaccination by a systematic literature search. The significance of these reports was limited since it is not clear if a coincidental or causal relationship exists between SARS-CoV-2 infection or vaccination and manifestation of NMDA receptor encephalitis. The included studies were hampered by difficulties in establishing if these patients had pre-existing NMDA receptor antibodies which entered the brain by infection- or vaccination-associated transient blood-brain barrier leakage. In addition, four cases had comorbid ovarian teratoma, which is a known trigger for development of NMDA receptor encephalitis. Considering that billions of people have contracted COVID-19 or have been vaccinated against this virus, the publication of only 19 case reports with a possible link to NMDA receptor encephalitis, indicates that it is rare. In conclusion, these findings do not support the case that SARS-CoV-2 infection or vaccination led to an increase of existing or de novo encephalitis mediated by an autoimmune response targeting NMDA receptor function. Nevertheless, this work underscores the importance of ongoing vigilance in monitoring viral outbreaks and their potential impact on the central nervous system through basic, epidemiological and translational research.

Digital technology and mental health during the COVID-19 pandemic: a narrative review with a focus on depression, anxiety, stress, and trauma.

The sudden appearance and devastating effects of the COVID-19 pandemic resulted in the need for multiple adaptive changes in societies, business operations and healthcare systems across the world. This review describes the development and increased use of digital technologies such as chat bots, electronic diaries, online questionnaires and even video gameplay to maintain effective treatment standards for individuals with mental health conditions such as depression, anxiety and post-traumatic stress syndrome. We describe how these approaches have been applied to help meet the challenges of the pandemic in delivering mental healthcare solutions. The main focus of this narrative review is on describing how these digital platforms have been used in diagnostics, patient monitoring and as a treatment option for the general public, as well as for frontline medical staff suffering with mental health issues.

Potential Cross-Links of Inflammation With Schizophreniform and Affective Symptoms: A Review and Outlook on Autoimmune Encephalitis and COVID-19.

Based on current implications of the SARS-CoV-2 pandemic with regards to mental health, we show that biological links exist between inflammation and mental illness in addition to psychoreactive effects. We describe key principles of the biological interaction of the immune system and the mind, as well as the possible routes of viral entry into the brain. In addition, we provide a stepwise scheme for the diagnosis and therapy of autoimmune-encephalitis with schizophrenia-like symptomatology as a general guide for clinical practice and in the specialized scenario of infections, such as those caused by the SARS-CoV-2 virus.