This study sought to characterize cognitive functioning in patients with neurological post-acute sequelae of SARS-CoV-2 infection (Neuro-PASC) and investigate the association of subjective and objective functioning along with other relevant factors with prior hospitalization for COVID-19. Participants were 106 adult outpatients with Neuro-PASC referred for abbreviated neuropsychological assessment after scoring worse than one standard deviation below the mean on cognitive screening. Of these patients, 23 had been hospitalized and 83 had not been hospitalized for COVID-19. Subjective cognitive impairment was evaluated with the self-report cognition subscale from the Patient-Reported Outcome Measurement Information System. Objective cognitive performance was assessed using a composite score derived from multiple standardized cognitive measures. Other relevant factors, including fatigue and depression/mood symptoms, were assessed via the Patient-Reported Outcome Measurement Information System. Subjective cognitive impairment measures exceeded the minimal difficulties noted on objective tests and were associated with depression/mood symptoms as well as fatigue. However, fatigue independently explained the most variance (17.51%) in patients\' subjective cognitive ratings. When adjusting for fatigue and time since onset of COVID-19 symptoms, neither objective nor subjective impairment were associated with prior hospitalization for COVID-19. Findings suggest that abbreviated neuropsychological assessment may not reveal objective difficulties beyond initial cognitive screening in patients with Neuro-PASC. However, subjective cognitive concerns may persist irrespective of hospitalization status, and are likely influenced by fatigue and depression/mood symptoms. The impact of concomitant management of fatigue and mood in patients with Neuro-PASC who report cognitive concerns deserve further study.

Aging leads to physiological changes, including inflammaging-a chronic low-grade inflammatory state with significant implications for various physiological systems, particularly for cardiovascular health. Concurrently, immunosenescence-the age-related decline in immune function, exacerbates vulnerabilities to cardiovascular pathologies in older individuals. Examining the dynamic connections between immunosenescence, inflammation, and cardiovascular aging, this mini-review aims to disentangle some of these interactions for a better understanding of their complex interplay. In the context of cardiovascular aging, the chronic inflammatory state associated with inflammaging compromises vascular integrity and function, contributing to atherosclerosis, endothelial dysfunction, arterial stiffening, and hypertension. The aging immune system\'s decline amplifies oxidative stress, fostering an environment conducive to atherosclerotic plaque formation. Noteworthy inflammatory markers, such as the high-sensitivity C-reactive protein, interleukin-6, interleukin-1β, interleukin-18, and tumor necrosis factor-alpha emerge as key players in cardiovascular aging, triggering inflammatory signaling pathways and intensifying inflammaging and immunosenescence. In this review we aim to explore the molecular and cellular mechanisms underlying inflammaging and immunosenescence, shedding light on their nuanced contributions to cardiovascular diseases. Furthermore, we explore the reciprocal relationship between immunosenescence and inflammaging, revealing a self-reinforcing cycle that intensifies cardiovascular risks. This understanding opens avenues for potential therapeutic targets to break this cycle and mitigate cardiovascular dysfunction in aging individuals. Furthermore, we address the implications of Long COVID, introducing an additional layer of complexity to the relationship between aging, immunosenescence, inflammaging, and cardiovascular health. Our review aims to stimulate continued exploration and advance our understanding within the realm of aging and cardiovascular health.

UNASSIGNED: Sleep disturbances are included in the six most commonly cited complaints in post-COVID-19 conditions. In order to find the optimal management approach and enhance Quality of Life (QoL), we intend to explore sleep disturbances that occur in post-COVID-19 conditions.
UNASSIGNED: This was a cross-sectional study conducted with interviews and questionnaires using the Pittsburgh Sleep Quality Index (PSQI) for assessing sleep quality, Insomnia Severity Index (ISI) for assessing insomnia, Epworth Sleepiness Scale (ESS) for assessing Excessive Daytime Sleepiness (EDS), STOP-BANG questionnaire for assessing Obstructive Sleep Apnea (OSA), and Short Form 36 (SF-36) for assessing QoL. We recruited respondents from several cities in Indonesia and performed an analysis to find the relationship between sleep disturbance and its association with QoL.
UNASSIGNED: This study involved 757 respondents. They were predominantly female, with a median age of 39 years, no comorbidities, and had exhibited mild COVID-19 severity. Subjects with post-COVID-19 conditions experienced insomnia, poor sleep quality, normal sleepiness, and low risk of OSA. Sleep quality caused role limitations due to decreased physical and mental health. Insomnia caused role limitations due to emotional and social functioning problems. Meanwhile, OSA only affected physical functioning.
UNASSIGNED: Numerous aspects of patients\' QoL are affected by sleep disturbance in post-COVID-19 conditions. A comprehensive approach and coordinated care pathways must be effectively managed to improve QoL among individuals experiencing sleep disturbance.

UNASSIGNED: Persistent post-infectious symptoms, predominantly fatigue, characterize Long COVID. This study investigated the efficacy of Myelophil (MYP), which contains metabolites extracted from Astragalus membranaceus and Salvia miltiorrhiza using 30% ethanol, in alleviating fatigue among subjects with Long COVID.
UNASSIGNED: In this prospective observational study, we enrolled subjects with significant fatigue related to Long COVID, using criteria of scores of 60 or higher on the modified Korean Chalder Fatigue scale (mKCFQ11), or five or higher on the Visual Analog Scale (VAS) for brain fog. Utilizing a single-arm design, participants were orally administered MYP (2,000 mg daily) for 4 weeks. Changes in fatigue severity were assessed using mKCFQ11, Multidimensional Fatigue Inventory (MFI-20), and VAS for fatigue and brain fog. In addition, changes in quality of life using the short form 12 (SF-12) were also assessed along with plasma cortisol levels.
UNASSIGNED: A total of 50 participants (18 males, 32 females) were enrolled; 49 were included in the intention-to-treat analysis with scores of 66.9 ± 11.7 on mKCFQ11 and 6.3 ± 1.5 on the brain fog VAS. After 4 weeks of MYP administration, there were statistically significant improvements in fatigue levels: mKCFQ11 was measured at 34.8 ± 17.1 and brain fog VAS at 3.0 ± 1.9. Additionally, MFI-20 decreased from 64.8 ± 9.8 to 49.3 ± 10.8, fatigue VAS dropped from 7.4 ± 1.0 to 3.4 ± 1.7, SF-12 scores rose from 53.3 ± 14.9 to 78.6 ± 14.3, and plasma cortisol levels also elevated from 138.8 ± 50.1 to 176.9 ± 62.0 /mL. No safety concerns emerged during the trial.
UNASSIGNED: Current findings underline MYP\'s potential in managing Long COVID-induced fatigue. However, comprehensive studies remain imperative.
UNASSIGNED: https://cris.nih.go.kr, identifier KCT0008948.

The COVID-19 pandemic has resulted in many therapies, of which many are repurposed and used for other diseases in the last decade such in Influenza and Ebola. We intend to provide a robust foundation for cardiovascular outcomes of the therapies to better understand the rationale for the clinical trials that were conducted during the COVID-19 pandemic, and to gain more clarity on the steps moving forward should the repurposing provide clinical benefit in pandemic situations. With this state-of-the-art review, we aim to improve the understanding of the cardiovascular involvement of the therapies prior to, during, and after the COVID-19 pandemic to provide meaningful findings to the cardiovascular specialists and clinical trials for therapies, moving on from the period of pandemic urgency.

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.
CONCLUSIONS: 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.

BACKGROUND: COVID-19 is primarily considered a respiratory tract infection, but it can also affect the central nervous system (CNS), which can result in long-term sequelae. In contrast to CNS infections by classic neurotropic viruses, SARS-CoV-2 is usually not detected in cerebrospinal fluid (CSF) from patients with COVID-19 with neurological involvement (neuro-COVID), suggesting fundamental differences in pathogenesis.
METHODS: To assess differences in CNS metabolism in neuro-COVID compared to CNS infections with classic neurotropic viruses, we applied a targeted metabolomic analysis of 630 metabolites to CSF from patients with (i) COVID-19 with neurological involvement [n = 16, comprising acute (n = 13) and post-COVID-19 (n = 3)], (ii) viral meningitis, encephalitis, or myelitis (n = 10) due to herpes simplex virus (n = 2), varicella zoster virus (n = 6), enterovirus (n = 1) and tick-borne encephalitis virus (n = 1), and (iii) aseptic neuroinflammation (meningitis, encephalitis, or myelitis) of unknown etiology (n = 21) as additional disease controls.
RESULTS: Standard CSF parameters indicated absent or low neuroinflammation in neuro-COVID. Indeed, CSF cell count was low in neuro-COVID (median 1 cell/µL, range 0-12) and discriminated it accurately from viral CNS infections (AUC = 0.99) and aseptic neuroinflammation (AUC = 0.98). 32 CSF metabolites passed quality assessment and were included in the analysis. Concentrations of differentially abundant (fold change ≥|1.5|, FDR ≤ 0.05) metabolites were both higher (9 and 5 metabolites) and lower (2 metabolites) in neuro-COVID than in the other two groups. Concentrations of citrulline, ceramide (d18:1/18:0), and methionine were most significantly elevated in neuro-COVID. Remarkably, triglyceride TG(20:1_32:3) was much lower (mean fold change = 0.09 and 0.11) in neuro-COVID than in all viral CNS infections and most aseptic neuroinflammation samples, identifying it as highly accurate biomarker with AUC = 1 and 0.93, respectively. Across all samples, TG(20:1_32:3) concentration correlated only moderately with CSF cell count (ρ = 0.65), protein concentration (ρ = 0.64), and Q-albumin (ρ = 0.48), suggesting that its low levels in neuro-COVID CSF are only partially explained by less pronounced neuroinflammation.
CONCLUSIONS: The results suggest that CNS metabolite responses in neuro-COVID differ fundamentally from viral CNS infections and aseptic neuroinflammation and may be used to discover accurate diagnostic biomarkers in CSF and to gain insights into differences in pathophysiology between neuro-COVID, viral CNS infections and aseptic neuroinflammation.

Long COVID is a condition that develops in a subset of patients after COVID-19 infection comprising of symptoms of varying severity encompassing multiple organ systems. Currently, long COVID is without consensus on a formal definition, identifiable biomarkers, and validated treatment. Long COVID is expected to be a long-term chronic condition for a subset of patients and is associated with suffering and incapacity. There is an urgent need for clear management guidelines for the primary care provider, who is essential in bridging the gap with more specialized care to improve quality of life and functionality in their patients living with long COVID. The purpose of this mini review is to provide primary care providers with the latest highlights from existing literature regarding the most common long COVID symptoms and current management recommendations. This review also highlights the underutilized interventions of stellate ganglion blocks and low-dose naltrexone, both with well-established safety profiles demonstrated to improve quality of life and functionality for patients suffering with some symptoms of long COVID, and encourages prompt referral to interventional pain management.

Acute SARS-CoV-2 infection triggers the generation of diverse and functional autoantibodies (AABs), even after mild cases. Persistently elevated autoantibodies have been found in some individuals with long COVID (LC). Using a >21,000 human protein array, we identified diverse AAB targets in LC patients that correlated with their symptoms. Elevated AABs to proteins in the nervous system were found in LC patients with neurocognitive and neurological symptoms. Purified Immunoglobulin G (IgG) samples from these individuals reacted with human pons tissue and were cross-reactive with mouse sciatic nerves, spinal cord, and meninges. Antibody reactivity to sciatic nerves and meninges correlated with patient-reported headache and disorientation. Passive transfer of IgG from patients to mice led to increased sensitivity and pain, mirroring patient-reported symptoms. Similarly, mice injected with IgG showed loss of balance and coordination, reflecting donor-reported dizziness. Our findings suggest that targeting AABs could benefit some LC patients.

UNASSIGNED: Insomnia, poor sleep quality and extremes of sleep duration are associated with COVID-19 infection. This study assessed whether these factors are related to Post-Acute Sequelae of SARS-CoV-2 infection (PASC).
UNASSIGNED: Cross-sectional survey of a general population of 24,803 U.S. adults to determine the association of insomnia, poor sleep quality and sleep duration with PASC.
UNASSIGNED: Prevalence rates of PASC among previously COVID-19 infected participants for three definitions of PASC were COPE (21.9%), NICE (38.9%) and RECOVER PASC Score (15.3%). PASC was associated with insomnia in all 3 models in fully adjusted models with adjusted odds ratios (aORs) and 95% confidence intervals (CI) ranging from 1.30 (95% CI: 1.11-1.52, p≤0.05, PASC Score) to 1.52 (95% CI: 1.34-1.71, p≤0.001, (NICE). Poor sleep quality was related to PASC in all models with aORs ranging from 1.77 (95% CI: 1.60-1.97, p≤0.001, NICE) to 2.00 (95% CI: 1.77-2.26, p≤0.001, COPE). Sleep <6 hours was associated with PASC with aORs between 1.59 (95% CI: 1.40-1.80, p≤0.001, PASC Score) to 1.70 (95% CI: 1.53-1.89, p≤0.001, COPE). Sleep ≥ 9 hours was not associated with PASC in any model. Although vaccination with COVID-19 booster decreased the likelihood of developing PASC, it did not attenuate associations between insomnia, poor sleep quality and short sleep duration with PASC in any of the models.
UNASSIGNED: Insomnia, poor sleep quality and short sleep duration are potential risk factors for PASC. Interventions to improve sleep may decrease the development of PASC.