Reinforcing the Evidence of Mitochondrial Dysfunction in Long COVID Patients Using a Multiplatform Mass Spectrometry-Based Metabolomics Approach.

Despite the recent and increasing knowledge surrounding COVID-19 infection, the underlying mechanisms of the persistence of symptoms for a long time after the acute infection are still not completely understood. Here, a multiplatform mass spectrometry-based approach was used for metabolomic and lipidomic profiling of human plasma samples from Long COVID patients (n = 40) to reveal mitochondrial dysfunction when compared with individuals fully recovered from acute mild COVID-19 (n = 40). Untargeted metabolomic analysis using CE-ESI(+/-)-TOF-MS and GC-Q-MS was performed. Additionally, a lipidomic analysis using LC-ESI(+/-)-QTOF-MS based on an in-house library revealed 447 lipid species identified with a high confidence annotation level. The integration of complementary analytical platforms has allowed a comprehensive metabolic and lipidomic characterization of plasma alterations in Long COVID disease that found 46 relevant metabolites which allowed to discriminate between Long COVID and fully recovered patients. We report specific metabolites altered in Long COVID, mainly related to a decrease in the amino acid metabolism and ceramide plasma levels and an increase in the tricarboxylic acid (TCA) cycle, reinforcing the evidence of an impaired mitochondrial function. The most relevant alterations shown in this study will help to better understand the insights of Long COVID syndrome by providing a deeper knowledge of the metabolomic basis of the pathology.

People with a connective tissue disorder may be especially vulnerable to the endothelial damage that characterizes long COVID due to the fragility of their vasculature and slow wound healing.

A growing body of evidence documents the central role that endothelial damage plays in the pathophysiology of long COVID. But it remains unclear why only certain people get Long COVID and why recovery times are so long for many affected individuals. One potential explanation is that some forms of long COVID are experienced disproportionately by people with a connective tissue disorder who are more vulnerable than others to incurring serious damage to the endothelium and the vascular extracellular matrix from the inflammatory processes triggered by COVID-19 and much slower to heal. Further research is needed to explore this hypothesis.

Potential pathophysiological role of the ion channel TRPM3 in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and the therapeutic effect of low-dose naltrexone.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating disease with a broad overlap of symptomatology with Post-COVID Syndrome (PCS). Despite the severity of symptoms and various neurological, cardiovascular, microvascular, and skeletal muscular findings, no biomarkers have been identified. The Transient receptor potential melastatin 3 (TRPM3) channel, involved in pain transduction, thermosensation, transmitter and neuropeptide release, mechanoregulation, vasorelaxation, and immune defense, shows altered function in ME/CFS. Dysfunction of TRPM3 in natural killer (NK) cells, characterized by reduced calcium flux, has been observed in ME/CFS and PCS patients, suggesting a role in ineffective pathogen clearance and potential virus persistence and autoimmunity development. TRPM3 dysfunction in NK cells can be improved by naltrexone in vitro and ex vivo, which may explain the moderate clinical efficacy of low-dose naltrexone (LDN) treatment. We propose that TRPM3 dysfunction may have a broader involvement in ME/CFS pathophysiology, affecting other organs. This paper discusses TRPM3's expression in various organs and its potential impact on ME/CFS symptoms, with a focus on small nerve fibers and the brain, where TRPM3 is involved in presynaptic GABA release.

Clinical and diagnostic features of long-COVID patients presenting with neurologic symptoms in Chicago.

Long COVID, a condition characterized by persistent symptoms after COVID-19 infection, is increasingly being recognized worldwide. Neurologic symptoms are frequently reported in survivors of COVID-19, making it crucial to better understand this phenomenon both on a societal scale and for the quality of life of these patients. Between January 1, 2020, and July 31, 2022, Illinois (IL) had a standardized cumulative death rate that ranked it 24th out of the 51 states in the United States (US). However, the US had one of the highest per capita COVID-19 death rates among large, high-income countries. [Bollyky T. et al. 2023] As a result of the increased number of COVID-19 infections, there was a rise in the number of patients experiencing Long COVID. At our neuro-infectious disease clinic in Chicago (IL), we observed an increasing number of patients presenting with cognitive and other neurologic symptoms after contracting COVID-19. Initially, we needed to provide these individuals with a better understanding of their condition and expected outcomes. We were thus motivated to further evaluate this group of patients for any patterns in presentation, neurologic findings, and diagnostic testing that would help us better understand this phenomenon. We aim to contribute to the growing body of research on Long COVID, including its presentation, diagnostic testing results, and outcomes to enlighten the long COVID syndrome. We hypothesize that the neurological symptoms resulting from long COVID persist for over 12 months. We conducted a retrospective analysis of clinical data from 44 patients with long-COVID. Cognitive symptoms were the most common presenting concern. Abnormalities in Montreal Cognitive Assessment, electroencephalogram, serum autoantibody testing, and cerebrospinal fluid were found in minority subsets of our cohort. At 12 months, most patients continue to experience neurologic symptoms, though more than half reported moderate or marked improvement compared to initial presentation. Although most of the patients in this study did not show a consistent occurrence of symptoms suggesting a cohesive underlying etiology, our clinical data demonstrated some features of Long COVID patients in Chicago (IL) that could lead to new research avenues, helping us better understand this syndrome that affects patients worldwide.

COVID-19 and cardiovascular disease in patients with chronic kidney disease.

Millions of people worldwide have chronic kidney disease (CKD). Affected patients are at high risk for cardiovascular (CV) disease for several reasons. Among various comorbidities, CKD is associated with the more severe forms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This is particularly true for patients receiving dialysis or for kidney recipients. From the start of the SARS-CoV-2 pandemic, several CV complications have been observed in affected subjects, spanning acute inflammatory manifestations, CV events, thrombotic episodes and arrythmias. Several pathogenetic mechanisms have been hypothesized, including direct cytopathic viral effects on the myocardium, endothelial damage and hypercoagulability. This spectrum of disease can occur during the acute phase of the infection, but also months after recovery. This review is focussed on the CV complications of coronavirus disease 2019 (COVID-19) with particular interest in their implications for the CKD population.

Long-term symptoms after SARS-CoV-2 infection in a cohort of hospital employees: duration and predictive factors.

PURPOSE: To evaluate the frequency, duration and patterns of long-term coronavirus disease 2019 (COVID-19) symptoms and to analyse risk factors for long-lasting COVID-19 sequelae among a cohort of hospital employees (HEs). METHODS: We conducted a survey regarding persistent COVID-19 related symptoms with all HEs from three medical centres in Cologne, Germany, who were tested SARS-CoV-2 PCR positive from March 2020 until May 2021. Duration of symptoms and possible risk factors for protracted COVID-19 course were analysed. RESULTS: Of 221 included HEs, a number of 104 HEs (47.1%) reported at least one persisting symptom for more than 90 days after initial SARS-CoV-2 detection. Each one cycle higher initial Ct value significantly increased the chances of overcoming symptoms (odds ratio [OR] 1.05; 95% confidence interval (95%CI) 1.01-1.09; p = 0.019). The occurrence of breathlessness within the first ten days (OR 7.89; 95%CI 1.87-41.43; p = 0.008), an initial Ct value under 30 (OR 3.36; 95%CI 1.22-9.94; p = 0.022) as well as the occurrence of anosmia or ageusia within the first ten days (OR 3.01; 95%CI 1.10-8.84; p = 0.037) showed a statistically significant association with increased odds of illness duration over 90 days. CONCLUSION: About half of the HEs suffered from long lasting symptoms over 90 days after almost entirely mild acute COVID-19. Predictive factors could possibly be used for early treatment to prevent development of long-term symptoms after COVID-19 in future.

Multimodal neuroimaging in post-COVID syndrome and correlation with cognition.

Brain changes have been reported in the first weeks after SARS-CoV-2 infection. However, limited literature exists about brain alterations in post-COVID syndrome, a condition increasingly associated with cognitive impairment. The present study aimed to evaluate brain functional and structural alterations in patients with post-COVID syndrome, and assess whether these brain alterations were related to cognitive dysfunction. Eighty-six patients with post-COVID syndrome and 36 healthy controls were recruited and underwent neuroimaging acquisition and a comprehensive neuropsychological assessment. Cognitive and neuroimaging examinations were performed 11 months after the first symptoms of SARS-CoV-2. Whole-brain functional connectivity analysis was performed. Voxel-based morphometry was performed to evaluate grey matter volume, and diffusion tensor imaging was carried out to analyse white-matter alterations. Correlations between cognition and brain changes were conducted and Bonferroni corrected. Post-COVID syndrome patients presented with functional connectivity changes, characterized by hypoconnectivity between left and right parahippocampal areas, and between bilateral orbitofrontal and cerebellar areas compared to controls. These alterations were accompanied by reduced grey matter volume in cortical, limbic and cerebellar areas, and alterations in white matter axial and mean diffusivity. Grey matter volume loss showed significant associations with cognitive dysfunction. These cognitive and brain alterations were more pronounced in hospitalized patients compared to non-hospitalized patients. No associations with vaccination status were found. The present study shows persistent structural and functional brain abnormalities 11 months after the acute infection. These changes are associated with cognitive dysfunction and contribute to a better understanding of the pathophysiology of the post-COVID syndrome.

How are Long-Covid, Post-Sepsis-Syndrome and Post-Intensive-Care-Syndrome related? A conceptional approach based on the current research literature.

Long-Covid (LC), Post-Sepsis-Syndrome (PSS) and Post-Intensive-Care-Syndrome (PICS) show remarkable overlaps in their clinical presentation. Nevertheless, it is unclear if they are distinct syndromes, which may co-occur in the same patient, or if they are three different labels to describe similar symptoms, assigned on the basis on patient history and professional perspective of the treating physician. Therefore, we reviewed the current literature on the relation between LC, PSS and PICS. To date, the three syndromes cannot reliably be distinguished due similarities in clinical presentation as they share the cognitive, psychological and physical impairments with only different probabilities of occurrence and a heterogeneity in individual expression. The diagnosis is furthermore hindered by a lack of specific diagnostic tools. It can be concluded that survivors after COVID-19 sepsis likely have more frequent and more severe consequences than patients with milder COVID-19 courses, and that are some COVID-19-specific sequelae, e.g. an increased risk for venous thromboembolism in the 30 days after the acute disease, which occur less often after sepsis of other causes. Patients may profit from leveraging synergies from PICS, PSS and LC treatment as well as from experiences gained from infection-associated chronic conditions in general. Disentangling molecular pathomechanisms may enable future targeted therapies that go beyond symptomatic treatment.

A review of post COVID syndrome pathophysiology, clinical presentation and management in children and young people.

Post Covid Syndrome (PCS) is a complex multi-system disorder with a spectrum of presentations. Severity ranges from mild to very severe with variable duration of illness and recovery. This paper discusses the difficulties defining and describing PCS. We review the current understanding of PCS, epidemiology, and predisposing factors. We consider potential mechanisms including viral persistence, clotting dysfunction and immunity. We review presentation and diagnosis and finally consider management strategies including addressing symptom burden, rehabilitation, and novel therapies.

Effects of cognitive training and group psychotherapy on cognitive performance of post COVID-19 patients: an exploratory and non-randomized clinical trial.

Cognitive complaints are common signs of the Post COVID-19 (PC) condition, but the extent and type of cognitive impairment may be heterogeneous. Little is known about neuropsychological treatment options. Preliminary evidence suggests cognitive symptoms may improve with cognitive training and naturally over time. In this clinical trial, we examined whether participation in a weekly group consisting of cognitive training and group psychotherapy is feasible and would exert beneficial effects on cognitive performance in PC and whether improvements were associated with intervention group participation or represented a temporal improvement effect during syndrome progression. 15 PC patients underwent an 8-week intervention. Cognitive performance was assessed before and after each intervention group participation. A control group of 15 PC patients with subjective neurocognitive or psychiatric complaints underwent two cognitive assessments with comparable time intervals without group participation. To attribute changes to the intervention group participation, interaction effects of group participation and time were checked for significance. This is an exploratory, non-randomized, non-blinded controlled clinical trial. Within the intervention group, significant improvements were found for most cognitive measures. However, significant time x group interactions were only detected in some dimensions of verbal memory and visuo-spatial construction skills. Significant time effects were observed for attention, concentration, memory, executive functions, and processing speed. The intervention setting was feasible and rated as helpful and relevant by the patients. Our results suggest that cognitive symptoms of PC patients may improve over time. Patients affected by both neurocognitive impairments and mental disorders benefit from group psychotherapy and neurocognitive training. The present study provides evidence for a better understanding of the dynamic symptomatology of PC and might help to develop further studies addressing possible therapy designs. The main limitations of this exploratory feasibility trial are the small sample size as well as the non-randomized design due to the clinical setting.

Definitions and symptoms of the post-COVID syndrome: an updated systematic umbrella review.

Post-COVID syndrome (PCS) describes a persistent complex of symptoms following a COVID-19 episode, lasting at least 4 to 12 weeks, depending on the specific criteria used for its definition. It is often associated with moderate to severe impairments of daily life and represents a major burden for many people worldwide. However, especially during the first two years of the COVID-19 pandemic, therapeutic and diagnostic uncertainties were prominent due to the novelty of the disease and non-specific definitions that overlooked functional deficits and lacked objective assessment. The present work comprehensively examines the status of PCS definitions as depicted in recent reviews and meta-analyses, alongside exploring associated symptoms and functional impairments. We searched the database Pubmed for reviews and meta-analysis evaluating PCS in the period between May 31, 2022, to December 31, 2023. Out of 95 studies, 33 were selected for inclusion in our analyses. Furthermore, we extended upon prior research by systematically recording the symptoms linked with PCS as identified in the studies. We found that fatigue, neurological complaints, and exercise intolerance were the most frequently reported symptoms. In conclusion, over the past eighteen months, there has been a notable increase in quantity and quality of research studies on PCS. However, there still remains a clear need for improvement, particularly with regard to the definition of the symptoms necessary for diagnosing this syndrome. Enhancing this aspect will render future research more comparable and precise, thereby advancing and understanding PCS.

Effects of an integrative multimodal inpatient program on fatigue and work ability in patients with Post-COVID Syndrome-a prospective observational study.

Post-COVID syndrome (PCS) is characterized by a variety of non-specific symptoms. One of the leading symptoms is fatigue. So far, there is no evidence-based causal therapy established and treatment of PCS is primarily symptom-oriented. The Clinic for Internal and Integrative Medicine in Bamberg, Germany, offers a comprehensive multimodal integrative inpatient therapy for PCS patients. Within a prospective uncontrolled observational study, the results of N = 79 patients were analysed. Post-COVID fatigue patients were hospitalized for up to 14 days. The treatment consists of individual modules depending on the patient's needs. It includes a wide range of integrative non-pharmacological treatment modalities. Outcomes were assessed before and after the inpatient treatment as well as 6 months after discharge from the hospital. Results show that fatigue of post-COVID patients in this study (M = 76.30, SD = 10.18, N = 64) was initially significantly higher than in the subsample "women aged 60-92 years" of the general German population (M = 51.5, Schwarz et al. [Schwarz et al. in Onkologie 26:140-144, 2003]; T(63) = 19.50, p < .001). Fatigue was significantly and clinically relevant reduced directly after discharge (MT1 = 76.21, SD = 11.38, N = 42; MT2 = 66.57, SD = 15.55, N = 42), F(1, 41) = 19.80, p < .001, partial eta squared = .326, as well as six months after discharge (MT3 = 65.31, SD = 17.20, N = 42), F(1, 41), p < .001, partial eta squared = .371. Additionally, self-reported ability to work (NRS, 0-10) improved significantly from admission (MT1 = 2.54, SD = 2.23, N = 39) to discharge (MT2 = 4.26, SD = 2.60, N = 39), F(1, 38) = 26.37, p < .001, partial eta squared = .410), as well as to six months later (MT3 = 4.41, SD = 3.23, N = 39), F(1, 38) = 15.00, p < .001, partial eta squared = .283. The study showed that patients suffering from chronic post-COVID syndrome for several months can achieve a significant improvement in their leading fatigue symptoms and a significant improvement in the subjective assessment of their ability to work through a comprehensive two-week multimodal integrative inpatient program.

Portrait of mental health identified by people with the post-covid syndrome.

OBJECTIVES: This study aimed to produce a patient-centered understanding of mental health symptoms of people with the post-COVID-19 syndrome (PCS). METHODS: A cross-sectional analysis of 414 participants in a longitudinal study was carried out involving people who self-identified as having symptoms of PCS. People were asked to name their most frequent and most bothersome mental health symptoms affected by PCS using the structure of the Patient Generated Index (PGI). The text threads from the PGI were grouped into topics using BERTopic analysis. RESULTS: 20 topics were identified from 818 text threads referring to PCS mental health symptoms. 35% of threads were identified as relating to anxiety, discussed in terms of five topics: generalized/social anxiety, fear/worry, post-traumatic stress, panic, and nervous. 29% of threads were identified as relating to low mood, represented by five topics: depression, discouragement, emotional distress, sadness, and loneliness. A cognitive domain (22% of threads) was covered by four topics referring to concentration, memory, brain fog, and mental fatigue. Topics related to frustration, anger, irritability. and mood swings (7%) were considered as one domain and there were separate topics related to motivation, insomnia, and isolation. CONCLUSIONS: This novel method of digital transformation of unstructured text data uncovered different ways in which people think about classical mental health domains. This information could be used to evaluate whether existing measures cover the content identified by people with PCS, to initiate a clinical conversation, or to justify the development of a new measure of the mental health impact of PCS.

Long COVID in pediatrics-epidemiology, diagnosis, and management.

This review summarizes current knowledge on post-acute sequelae of COVID-19 (PASC) and post-COVID-19 condition (PCC) in children and adolescents. A literature review was performed to synthesize information from clinical studies, expert opinions, and guidelines. PASC also termed Long COVID - at any age comprise a plethora of unspecific symptoms present later than 4 weeks after confirmed or probable infection with severe respiratory syndrome corona virus type 2 (SARS-CoV-2), without another medical explanation. PCC in children and adolescents was defined by the WHO as PASC occurring within 3 months of acute coronavirus disease 2019 (COVID-19), lasting at least 2 months, and limiting daily activities. Pediatric PASC mostly manifest after mild courses of COVID-19 and in the majority of cases remit after few months. However, symptoms can last for more than 1 year and may result in significant disability. Frequent symptoms include fatigue, exertion intolerance, and anxiety. Some patients present with postural tachycardia syndrome (PoTS), and a small number of cases fulfill the clinical criteria of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). To date, no diagnostic marker has been established, and differential diagnostics remains challenging. Therapeutic approaches include appropriate self-management as well as the palliation of symptoms by non-pharmaceutical and pharmaceutical strategies.    Conclusion: PASC in pediatrics present with heterogenous severity and duration. A stepped, interdisciplinary, and individualized approach is essential for appropriate clinical management. Current health care structures have to be adapted, and research was extended to meet the medical and psychosocial needs of young people with PASC or similar conditions. What is Known: • Post-acute sequelae of coronavirus 2019 (COVID-19) (PASC) - also termed Long COVID - in children and adolescents can lead to activity limitation and reduced quality of life. • PASC belongs to a large group of similar post-acute infection syndromes (PAIS). Specific biomarkers and causal treatment options are not yet available. What is New: • In February 2023, a case definition for post COVID-19 condition (PCC) in children and adolescents was provided by the World Health Organization (WHO), indicating PASC with duration of at least 2 months and limitation of daily activities. PCC can present as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). • Interdisciplinary collaborations are necessary and have been established worldwide to offer harmonized, multimodal approaches to diagnosis and management of PASC/PCC in children and adolescents.

Personalised Health Behaviour Support Programme in Adults With Post-COVID Syndrome: A Randomised, Controlled Pilot Feasibility Trial.

BACKGROUND: We investigated whether a novel 8-week personalised health behaviour support programme, focusing on the stability of symptoms and strategies to improve activities of daily living, was feasible and acceptable in adults with post-COVID syndrome. METHODS: In this randomised, controlled, pilot feasibility trial, 32 adults with post-COVID syndrome (continued symptoms for ≥ 12 weeks) were randomised 1:1 to receive personalised health behaviour support (self-reported physical activity and symptom diaries, plus seven one-to-one remotely delivered personalised self-management support sessions), once weekly for 8-weeks, or usual care (referral to online 'your COVID-19 recovery' programme). The primary outcome was the feasibility of recruiting and randomising adults with post-COVID syndrome. The secondary outcomes were to assess the acceptability and safety of the intervention and various outcome measures. RESULTS: Of the 48 adults who expressed interest in the study, 32 (67%) were eligible and completed the baseline assessment. All 32 adults were willing to be randomised to either the personalised health behaviour support programme (n = 17) or usual care (n = 15) and 27 (age: 45 ± 12 years) adults completed follow-up at 9 weeks. The intervention was deemed feasible, with high adherence (92% and 94% completion rates for the physical activity and symptom diaries, respectively) and excellent acceptability rates (94% 'liked the intervention a lot'). The intervention was deemed safe, with no symptom exacerbations reported. CONCLUSION: An 8-week personalised health behaviour support programme was feasible for adults with post-COVID syndrome, with good adherence and acceptability rates. Early pilot data from this small sample also suggests meaningful improvements in physical activity, fatigue and respiratory symptoms. PATIENT OR PUBLIC CONTRIBUTION: People living with post-COVID syndrome were involved from the outset with the study design, review of study documentation and interpretation of the data following completion. Furthermore, several participants have supported the local dissemination of findings following the completion of the study.

Virtual pulmonary rehabilitation approaches in patients with post COVID syndrome: a pilot study.

BACKGROUND: The characteristics of optimal virtual pulmonary rehabilitation (PR) for individuals with post-COVID syndrome (PCS) have not been identified. This study aimed to assess the feasibility, safety, and satisfaction associated with a virtual PR program with the exercise component delivered through group or self-directed sessions. METHODS: Adults with PCS-respiratory symptoms were randomly assigned to the video conference (PRVC) or self-directed (PRSD) group and completed an exercise program (aerobic, strengthening, and breathing exercises) three times/week for eight weeks. PRVC sessions were led by a physiotherapist via Zoom, whereas the PRSD group exercised individually following a pre-recorded video. Both groups received personalized exercise recommendations, education related to the condition, and a weekly follow up call. Satisfaction was assessed through a patient survey. Lung function, dyspnea, fatigue, sit-to-stand capacity, health-related quality of life, and participation were assessed pre- and post-PR. RESULTS: Fourteen PCS individuals (49 ± 9 years, 86% females) completed 83% of the sessions. All participants were satisfied with information provided by the therapist and frequency of data submission, whereas most were satisfied with the frequency and duration of exercise sessions (88% in PRVC and 83% in PRSD). A higher proportion of participants in the PRVC (88%) were satisfied with the level of difficulty of exercises compared with the PRSD (67%), and 84% of the sample reported a positive impact of the program on their health. No adverse events were reported. Significant changes in sit-to-stand capacity (p = 0.012, Cohen's r = 0.67) and questions related to fatigue (p = 0.027, Cohen's r = 0.58), neurocognitive (p = 0.045, Cohen's r = 0.53), and autonomic (p = 0.024, Cohen's r = 0.60) domains of the DePaul Symptom Questionnaire short-form were also found between groups. CONCLUSION: Virtual PR with exercises delivered via video conference or pre-recorded video were feasible, safe, and well-received by individuals with PCS. TRIAL REGISTRATION: NCT05003271 (first posted: 12/08/2021).

Post-COVID syndrome prevalence: a systematic review and meta-analysis.

BACKGROUND: Since the Coronavirus disease 2019 (COVID-19) pandemic began, the number of individuals recovering from COVID-19 infection have increased. Post-COVID Syndrome, or PCS, which is defined as signs and symptoms that develop during or after infection in line with COVID-19, continue beyond 12 weeks, and are not explained by an alternative diagnosis, has also gained attention. We systematically reviewed and determined the pooled prevalence estimate of PCS worldwide based on published literature. METHODS: Relevant articles from the Web of Science, Scopus, PubMed, Cochrane Library, and Ovid MEDLINE databases were screened using a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-guided systematic search process. The included studies were in English, published from January 2020 to April 2024, had overall PCS prevalence as one of the outcomes studied, involved a human population with confirmed COVID-19 diagnosis and undergone assessment at 12 weeks post-COVID infection or beyond. As the primary outcome measured, the pooled prevalence of PCS was estimated from a meta-analysis of the PCS prevalence data extracted from individual studies, which was conducted via the random-effects model. This study has been registered on PROSPERO (CRD42023435280). RESULTS: Forty eight studies met the eligibility criteria and were included in this review. 16 were accepted for meta-analysis to estimate the pooled prevalence for PCS worldwide, which was 41.79% (95% confidence interval [CI] 39.70-43.88%, I2 = 51%, p = 0.03). Based on different assessment or follow-up timepoints after acute COVID-19 infection, PCS prevalence estimated at ≥ 3rd, ≥ 6th, and ≥ 12th months timepoints were each 45.06% (95% CI: 41.25-48.87%), 41.30% (95% CI: 34.37-48.24%), and 41.32% (95% CI: 39.27-43.37%), respectively. Sex-stratified PCS prevalence was estimated at 47.23% (95% CI: 44.03-50.42%) in male and 52.77% (95% CI: 49.58-55.97%) in female. Based on continental regions, pooled PCS prevalence was estimated at 46.28% (95% CI: 39.53%-53.03%) in Europe, 46.29% (95% CI: 35.82%-56.77%) in America, 49.79% (95% CI: 30.05%-69.54%) in Asia, and 42.41% (95% CI: 0.00%-90.06%) in Australia. CONCLUSION: The prevalence estimates in this meta-analysis could be used in further comprehensive studies on PCS, which might enable the development of better PCS management plans to reduce the effect of PCS on population health and the related economic burden.

"Brain Fog" After COVID-19 Infection: How the Field of Neuropsychology Can Help Clear the Air.

The chapter explores the role of neuropsychology in understanding brain fog as a subjective complaint in the context of COVID-19. It discusses the historical and medical significance of the term "brain fog" and its psychological and neurological aspects. The chapter identifies the cognitive domains commonly affected by brain fog, such as attention, executive function, memory, and language. Additionally, it emphasizes the impact of societal changes during the COVID-19 pandemic on the general population as a crucial backdrop for understanding the issue. The chapter also highlights the important role of clinical and research neuropsychologists in gaining clarity on grouped data and individual patients' cognitive and emotional difficulties after COVID-19 infection. It discusses indications for neuropsychological rehabilitation and therapy and describes typical therapy phases and methods, including new approaches like telemedicine, virtual reality, and mobile app-based rehabilitation and self-tracking. The chapter underscores that experiences of brain fog can vary among COVID-19 patients and may change over time. It provides clinicians and interested parties with an in-depth understanding of brain fog and its manifestations, concomitant subtypes, and concrete strategies for addressing it. The chapter emphasizes the critical role of neuropsychology in scientifically examining brain fog and advocating for personalized approaches to cognitive rehabilitation.

Effects of an 8-week high-dose vitamin D supplementation on fatigue and neuropsychiatric manifestations in post-COVID syndrome: A randomized controlled trial.

AIM: This study evaluated the effectiveness of high-dose vitamin D supplementation in alleviating fatigue and neuropsychiatric symptoms in post-COVID syndrome. METHODS: In an 8-week, double-blind, randomized, placebo-controlled trial, 80 patients with post-COVID fatigue or neuropsychiatric symptoms were enrolled. Participants were randomly assigned to receive either 60,000 IU of vitamin D weekly (n = 40) or a placebo (n = 40) for 8 weeks. Clinical outcomes were assessed using the 11-item Chalder Fatigue Scale (CFQ-11); 21-item Depression, Anxiety, and Stress Scale (DASS-21); Pittsburgh Sleep Quality Index (PSQI); Addenbrooke's Cognitive Examination III (ACE); and Trail Making Test A and B (TMT-A and TMT-B). Baseline and 8-week measurements of inflammatory markers, including interleukin 6 (IL-6) and C-reactive protein (CRP), were also collected. RESULTS: Significant improvements were found in the vitamin D group for CFQ (coefficient -3.5, P = 0.024), DASS-anxiety (-2.0, P = 0.011), and ACE (2.1, P = 0.012). No significant differences were observed in PSQI, DASS-depression, TMT, IL-6, or CRP levels. The incidence of adverse events was comparable between groups, with no serious adverse events reported. CONCLUSION: High-dose vitamin D supplementation may benefit patients with post-COVID syndrome by reducing fatigue, alleviating anxiety, and improving cognitive symptoms, with minimal side effects.

Long COVID: lights and shadows on the clinical characterization of this emerging pathology.

More than 800 million individuals have contracted SARSCOV2 infection worldwide. It was estimated that almost 10-20% of these might suffer from Long COVID. It is a multisystemic syndrome, which negatively affects the quality of life with a significant burden of health loss compared to COVID negative individuals. Moreover, the risk of sequelae still remains high at 2 years in both nonhospitalized and hospitalized individuals. This review summarizes studies regarding long COVID and clarifies the definitions, the risk factors and the management of this syndrome. Finally, it delves into the most frequent long-term outcomes, especially postural orthostatic tachycardia syndrome" (POTS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), brain fog, and their therapeutical possibilities.