Long-COVID fatigue is not predicted by pre-pandemic plasma IL-6 levels in mild COVID-19.

OBJECTIVE AND DESIGN: Fatigue is a prominent symptom in the general population and may follow viral infection, including SARS-CoV2 infection which causes COVID-19. Chronic fatigue lasting more than three months is the major symptom of the post-COVID syndrome (known colloquially as long-COVID). The mechanisms underlying long-COVID fatigue are unknown. We hypothesized that the development of long-COVID chronic fatigue is driven by the pro-inflammatory immune status of an individual prior to COVID-19. SUBJECTS AND METHODS: We analyzed pre-pandemic plasma levels of IL-6, which plays a key role in persistent fatigue, in N = 1274 community dwelling adults from TwinsUK. Subsequent COVID-19-positive and -negative participants were categorized based on SARS-CoV-2 antigen and antibody testing. Chronic fatigue was assessed using the Chalder Fatigue Scale. RESULTS: COVID-19-positive participants exhibited mild disease. Chronic fatigue was a prevalent symptom among this population and significantly higher in positive vs. negative participants (17% vs 11%, respectively; p = 0.001). The qualitative nature of chronic fatigue as determined by individual questionnaire responses was similar in positive and negative participants. Pre-pandemic plasma IL-6 levels were positively associated with chronic fatigue in negative, but not positive individuals. Raised BMI was associated with chronic fatigue in positive participants. CONCLUSIONS: Pre-existing increased IL-6 levels may contribute to chronic fatigue symptoms, but there was no increased risk in individuals with mild COVID-19 compared with uninfected individuals. Elevated BMI also increased the risk of chronic fatigue in mild COVID-19, consistent with previous reports.

Online singing interventions for postnatal depression in times of social isolation: a feasibility study protocol for the SHAPER-PNDO single-arm trial.

BACKGROUND: Postnatal depression (PND) affects 13% of new mothers, with numbers rising during the COVID-19 pandemic. Despite this prevalence, many women have difficulty with or hesitancy towards accessing pharmacological and/or psychological interventions. Group-based mother-baby activities, however, have a good uptake, with singing improving maternal mental health and the mother-infant relationship. The recent lockdowns highlight the importance of adapting activities to an online platform that is wide-reaching and accessible. AIMS: The SHAPER-PNDO study will primarily analyse the feasibility of a 6-week online singing intervention, Melodies for Mums (M4M), for mothers with PND who are experiencing barriers to treatment. The secondary aim of the SHAPER-PNDO study will be to analyse the clinical efficacy of the 6-week M4M intervention for symptoms of postnatal depression. METHODS: A total of 120 mothers and their babies will be recruited for this single-arm study. All dyads will attend 6 weekly online singing sessions, facilitated by Breathe Arts Health Research. Assessments will be conducted on Zoom at baseline and week 6, with follow-ups at weeks 16 and 32, and will contain interviews for demographics, mental health, and social circumstances, and biological samples will be taken for stress markers. Qualitative interviews will be undertaken to understand the experiences of women attending the sessions and the facilitators delivering them. Finally, data will be collected on recruitment, study uptake and attendance of the programme, participant retention, and acceptability of the intervention. DISCUSSION: The SHAPER-PNDO study will focus on the feasibility, alongside the clinical efficacy, of an online delivery of M4M, available to all mothers with PND. We hope to provide a more accessible, effective treatment option for mothers with PND that can be available both during and outside of the pandemic for mothers who would otherwise struggle to attend in-person sessions, as well as to prepare for a subsequent hybrid RCT. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04857593 . Registered retrospectively on 22 April 2021. The first participants were recruited on 27 January 2021, and the trial is ongoing.

Neurogenesis is disrupted in human hippocampal progenitor cells upon exposure to serum samples from hospitalized COVID-19 patients with neurological symptoms.

Coronavirus disease 2019 (COVID-19), represents an enormous new threat to our healthcare system and particularly to the health of older adults. Although the respiratory symptoms of COVID-19 are well recognized, the neurological manifestations, and their underlying cellular and molecular mechanisms, have not been extensively studied yet. Our study is the first one to test the direct effect of serum from hospitalised COVID-19 patients on human hippocampal neurogenesis using a unique in vitro experimental assay with human hippocampal progenitor cells (HPC0A07/03 C). We identify the different molecular pathways activated by serum from COVID-19 patients with and without neurological symptoms (i.e., delirium), and their effects on neuronal proliferation, neurogenesis, and apoptosis. We collected serum sample twice, at time of hospital admission and approximately 5 days after hospitalization. We found that treatment with serum samples from COVID-19 patients with delirium (n = 18) decreased cell proliferation and neurogenesis, and increases apoptosis, when compared with serum samples of sex- and age-matched COVID-19 patients without delirium (n = 18). This effect was due to a higher concentration of interleukin 6 (IL6) in serum samples of patients with delirium (mean ± SD: 229.9 ± 79.1 pg/ml, vs. 32.5 ± 9.5 pg/ml in patients without delirium). Indeed, treatment of cells with an antibody against IL6 prevented the decreased cell proliferation and neurogenesis and the increased apoptosis. Moreover, increased concentration of IL6 in serum samples from delirium patients stimulated the hippocampal cells to produce IL12 and IL13, and treatment with an antibody against IL12 or IL13 also prevented the decreased cell proliferation and neurogenesis, and the increased apoptosis. Interestingly, treatment with the compounds commonly administered to acute COVID-19 patients (the Janus kinase inhibitors, baricitinib, ruxolitinib and tofacitinib) were able to restore normal cell viability, proliferation and neurogenesis by targeting the effects of IL12 and IL13. Overall, our results show that serum from COVID-19 patients with delirium can negatively affect hippocampal-dependent neurogenic processes, and that this effect is mediated by IL6-induced production of the downstream inflammatory cytokines IL12 and IL13, which are ultimately responsible for the detrimental cellular outcomes.

A Protocol to Understand the Implementation and Experiences of an Online Community-Based Performance Arts Programme Through and Beyond the COVID-19 Pandemic, Brain Waves

Introduction Individuals living with acquired brain injury experience numerous psychological, physical, and social challenges. Since the COVID-19 pandemic, many have experienced additional isolation, mental health issues and have had limited access to social and physical activities otherwise available in the community. Materials and Methods Brain Waves is a 12-week online performance arts programme developed during the COVID-19 pandemic, for people with acquired brain injury (ABI). The research component of Brain Waves is a qualitative study, using Interpretative Phenomenological Analysis (IPA) and ethnographic methods (Observations and Interviews). The study will recruit two distinct populations: individuals living with acquired brain injury (including people who have experienced traumatic brain injury and stroke who are participating in the programme) and stakeholders (facilitators, involved in the delivery of Brain Waves). This paper presents the protocol for a project which aims to gain an understanding of the implementation and experiences of creating and participating in an online community-based performance arts programme.

Long COVID and long chain fatty acids (LCFAs): Psychoneuroimmunity implication of omega-3 LCFAs in delayed consequences of COVID-19.

The global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the lasting pandemic of coronavirus disease 2019 (COVID-19) and the post-acute phase sequelae of heterogeneous negative impacts in multiple systems known as the "long COVID." The mechanisms of neuropsychiatric complications of long COVID are multifactorial, including long-term tissue damages from direct CNS viral involvement, unresolved systemic inflammation and oxidative stress, maladaptation of the renin-angiotensin-aldosterone system and coagulation system, dysregulated immunity, the dysfunction of neurotransmitters and hypothalamus-pituitaryadrenal (HPA) axis, and the psychosocial stress imposed by societal changes in response to this pandemic. The strength of safety, well-acceptance, and accumulating scientific evidence has now afforded nutritional medicine a place in the mainstream of neuropsychiatric intervention and prophylaxis. Long chain omega-3 polyunsaturated fatty acids (omega-3 or n-3 PUFAs) might have favorable effects on immunity, inflammation, oxidative stress and psychoneuroimmunity at different stages of SARS-CoV-2 infection. Omega-3 PUFAs, particularly EPA, have shown effects in treating mood and neurocognitive disorders by reducing pro-inflammatory cytokines, altering the HPA axis, and modulating neurotransmission via lipid rafts. In addition, omega-3 PUFAs and their metabolites, including specialized pro-resolvin mediators, accelerate the process of cleansing chronic inflammation and restoring tissue homeostasis, and therefore offer a promising strategy for Long COVID. In this article, we explore in a systematic review the putative molecular mechanisms by which omega-3 PUFAs and their metabolites counteract the negative effects of long COVID on the brain, behavior, and immunity.

Evaluation of a community-based performance arts programme for people who have experienced stroke in the UK: protocol for the SHAPER-Stroke Odysseys study.

INTRODUCTION: Stroke survivors, once in the community, face challenges with their long-term rehabilitation care and present higher levels of loneliness, depression and anxiety than the rest of the population. A community-based performance arts programme, Stroke Odysseys (SO), has been devised to tackle the challenges of living with stroke in the UK. In this study, we aim to evaluate the implementation, impact and experiences of SO for stroke survivors. METHODS AND ANALYSIS: Scaling-up Health Arts Programmes: Implementation and Effectiveness Research (SHAPER)-SO aims to scale-up SO to 75 participants and 47 stakeholders, while simultaneously evaluating the effectiveness and implementation of the programme. The main research aim is to evaluate the implementation, effectiveness, impact and experiences of a community-based performance arts programme (SO for stroke survivors). This mixed-methods study will evaluate the experience and impact of SO on those participating using mixed methods (interviews, observations and surveys) before and after each stage and carry out non-participant observations during a percentage of the workshops, training and tour. Data will be analysed using quantitative and qualitative approaches. This is a study within the SHAPER programme. ETHICS AND DISSEMINATION: Ethical approval has been granted by the King's College London PNM Research Ethics Panel, REC reference: LRS/DP-20/21-21549. Written informed consent will be sought for participants and stakeholders. The results of the study will be reported and disseminated at international conferences and in peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NCT04864470.

Self-guided Cognitive Behavioral Therapy Apps for Depression: Systematic Assessment of Features, Functionality, and Congruence With Evidence.

BACKGROUND: Mental health disorders affect 1 in 10 people globally, of whom approximately 300 million are affected by depression. At least half of the people affected by depression remain untreated. Although cognitive behavioral therapy (CBT) is an effective treatment, access to mental health specialists, habitually challenging, has worsened because of the COVID-19 pandemic. Internet-based CBT is an effective and feasible strategy to increase access to treatment for people with depression. Mental health apps may further assist in facilitating self-management for people affected by depression; however, accessing the correct app may be cumbersome given the large number and wide variety of apps offered by public app marketplaces. OBJECTIVE: This study aims to systematically assess the features, functionality, data security, and congruence with evidence of self-guided CBT-based apps targeting users affected by depression that are available in major app stores. METHODS: We conducted a systematic assessment of self-guided CBT-based apps available in Google Play and the Apple App Store. Apps launched or updated since August 2018 were identified through a systematic search in the 42matters database using CBT-related terms. Apps meeting the inclusion criteria were downloaded and assessed using a Samsung Galaxy J7 Pro (Android 9) and iPhone 7 (iOS 13.3.1). Apps were appraised using a 182-question checklist developed by the research team, assessing their general characteristics, technical aspects and quality assurance, and CBT-related features, including 6 evidence-based CBT techniques (ie, psychoeducation, behavioral activation, cognitive restructuring, problem solving, relaxation, and exposure for comorbid anxiety) as informed by a CBT manual, CBT competence framework, and a literature review of internet-based CBT clinical trial protocols. The results were reported as a narrative review using descriptive statistics. RESULTS: The initial search yielded 3006 apps, of which 98 met the inclusion criteria and were systematically assessed. There were 20 well-being apps; 65 mental health apps, targeting two or more common mental health disorders, including depression; and 13 depression apps. A total of 28 apps offered at least four evidence-based CBT techniques, particularly depression apps. Cognitive restructuring was the most common technique, offered by 79% (77/98) of the apps. Only one-third of the apps offered suicide risk management resources, whereas 17% (17/98) of the apps offered COVID-19-related information. Although most apps included a privacy policy, only a third of the apps presented it before account creation. In total, 82% (74/90) of privacy policies stated sharing data with third-party service providers. Half of the app development teams included academic institutions or health care providers. CONCLUSIONS: Only a few self-guided CBT-based apps offer comprehensive CBT programs or suicide risk management resources. Sharing of users' data is widespread, highlighting shortcomings in health app market governance. To fulfill their potential, self-guided CBT-based apps should follow evidence-based clinical guidelines, be patient centered, and enhance users' data security.

What can neuroimmunology teach us about the symptoms of long-COVID?

Long-Coronavirus Disease (Long-COVID) is becoming increasingly recognized due to the persistence of symptoms such as profound fatigue, neurocognitive difficulties, muscle pains and weaknesses and depression, which would last beyond 3-12 weeks following infection with SARS-CoV-2. These particular symptoms have been extensively observed and studied in the context of previous psychoneuroimmunology research. In this short commentary, we discuss how previous neuroimmunology studies could help us to better understand pathways behind the development of these prolonged symptoms. Various mechanisms, including viral neuroinvasion, glial cells activation, neurogenesis, oxidative stress have been shown to explain these symptoms in the context of other disorders. Previous neuroimmunology findings could represent helpful pointers for future research on long-COVID symptoms and suggest potential management strategies for patients suffering with long-COVID.

The three frontlines against COVID-19: Brain, Behavior, and Immunity.

The pandemic outbreak of coronavirus disease 2019 (COVID-19) is raising global anxiety and fear of both real and perceived health threat from the virus. Overwhelming evidence shows infected patients experiencing neuropsychiatric complications, suggesting that the "psychoneuroimmunity" model might be beneficial in understanding the impact of the virus. Therefore, this Special Issue on "Immunopsychiatry of COVID-19 Pandemic" was launched immediately after the pandemic was declared, with the first paper accepted on the March 25th, 2020. A total of ninety-three papers were accepted, the last one was on the July 10th, 2020 when the initial acute phase started declining. The papers of this Special Issue have illuminated the social impact, psychopathology, neurological manifestation, immunity responses, and potential treatments and prevention on COVID-19. For example, anxiety disorders, mood disorders, and suicidal ideation are most common psychiatric manifestations. COVID-19 infection can have central and/or peripheral nervous system symptoms, including headache, sleep disorders, encephalopathy, and loss of taste and smell. A "three-steps" Neuro-COVID infection model (neuro-invasion, clearance and immune response) was established. The current therapeutic interventions for COVID-19 include supportive intervention, immunomodulatory agents, antiviral therapy, and plasma transfusion. Psychological support should be implemented, improving the psychological wellbeing, as well as to enhance psychoneuroimmunity against COVID-19.

Omega-3 fatty acids in the psychological and physiological resilience against COVID-19.

As the infected cases of COVID-19 reach more than 20 million with more than 778,000 deaths globally, an increase in psychiatric disorders including anxiety and depression has been reported. Scientists globally have been searching for novel therapies and vaccines to fight against COVID-19. Improving innate immunity has been suggested to block progression of COVID-19 at early stages, while omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been shown to have immunomodulation effects. Moreover, n-3 PUFAs have also been shown to improve mood disorders, thus, future research is warranted to test if n-3 PUFAs may have the potential to improve our immunity to counteract both physical and mental impact of COVID-19.