CE-MS-Based Clinical Metabolomics of Human Plasma.

Capillary electrophoresis coupled to mass spectrometry (CE-MS) has emerged as a powerful analytical technique with significant implications for clinical research and diagnostics. The integration of information from CE and MS strengthens confidence in the identification of compounds present in clinical samples. The ability of CE to separate molecules based on their electrophoretic mobility coupled to MS enables the accurate identification and quantification of analytes, even in complex biological matrices such as human plasma.Here, we present a detailed protocol for an untargeted metabolomics study using CE-MS and its application in a study on human plasma from patients suffering Long COVID syndrome. The protocol ranges from sample preparation to biological interpretation, detailing a workflow enabling the analysis of cationic and anionic compounds, metabolite identification, and data processing.

Exploring the role of galectin-9 and artemin as biomarkers in long COVID with chronic fatigue syndrome: links to inflammation and cognitive function.

This study aimed to assess plasma galectin-9 (Gal-9) and artemin (ARTN) concentrations as potential biomarkers to differentiate individuals with Long COVID (LC) patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) from SARS-CoV-2 recovered (R) and healthy controls (HCs). Receiver operating characteristic (ROC) curve analysis determined a cut-off value of plasma Gal-9 and ARTN to differentiate LC patients from the R group and HCs in two independent cohorts. Positive correlations were observed between elevated plasma Gal-9 levels and inflammatory markers (e.g. SAA and IP-10), as well as sCD14 and I-FABP in LC patients. Gal-9 also exhibited a positive correlation with cognitive failure scores, suggesting its potential role in cognitive impairment in LC patients with ME/CFS. This study highlights plasma Gal-9 and/or ARTN as sensitive screening biomarkers for discriminating LC patients from controls. Notably, the elevation of LPS-binding protein in LC patients, as has been observed in HIV infected individuals, suggests microbial translocation. However, despite elevated Gal-9, we found a significant decline in ARTN levels in the plasma of people living with HIV (PLWH). Our study provides a novel and important role for Gal-9/ARTN in LC pathogenesis.

Liver function abnormality on admission predicts long COVID syndrome in digestive system.

Background: Clinical practice showed that many patients with SARS-CoV-2 infection presented with long COVID syndrome in digestive system. We sought to investigate the factor affecting the incidence of long COVID syndrome in digestive system. Methods and results: Patients with SARS-CoV-2 infection diagnosed at two centers of Zhongshan Hospital and one center of Shanghai Pudong Hospital from March 01, 2022 to May 31, 2022 were enrolled, collected in the hospital database, and followed up until March 30, 2023. The primary outcome of the study was the occurrence of post-acute sequelae of COVID-19 in the digestive system (long COVID syndrome). Modified Poisson regression was used to calculate the relative risk (RR). This cohort study included 494 patients with SARS-CoV-2 infection, 144 (29.1 %) patients developed liver function abnormality on admission. During the follow-up period, the primary study outcome occurred in 30 (20.8 %) of the group presenting with liver function abnormality on admission and in 20 (5.7 %) of the group without liver function abnormality on admission (adjusted, RR = 3.550, 95%CI: 2.099-6.006, P ≤ 0.001). Conclusion: Our study suggests that patients with COVID-19 who experience liver function abnormality on admission have an increased risk of developing long COVID syndrome in the digestive system.

Effects of aerobic training on cardiopulmonary fitness in patients with long COVID-19: a randomized controlled trial.

BACKGROUND: Long COVID-19 is characterized by systemic deterioration of the entire body, leading to significant physical and mental disorders. Exercise training has the potential to improve persistent symptoms and cardiopulmonary functions. METHOD: This was a single-center, randomized, controlled trial. Twenty-four patients aged 18 to 75 years who had a history of SARS-CoV-2 infection and long COVID symptoms. Patients were randomly allocated in a 1:1 ratio to receive either a 4-week exercise training program or an attention control group. The training group participated in 12 supervised aerobic sessions on a cycling ergometer over 4 weeks. The outcomes were to assess the impact of a 4-week aerobic exercise on the persistent symptoms and cardiopulmonary fitness, the surrogate endpoints of COVID-19 recovery and cardiopulmonary health. RESULTS: After the 4-week intervention, significant reductions were observed in the total number of symptoms in the training group. Specifically, 67.8% of patients in the training group exhibited reduced or completely resolved symptoms, in comparison to 16.7% in the control group (P = 0.013). After adjusting for gender, significant improvements in the training group were observed for exercise time (Pgroup*time = 0.028), maximum load (Pgroup*time = 0.01), and peak VO2 (Pgroup*time = 0.001), as well as O2 pulse (Pgroup*time = 0.042) and maximum heart rate (Pgroup*time = 0.007). The score of Short Form-12, depression, anxiety, perceived stress, and insomnia did not show significant changes between groups (Pgroup*time > 0.05). CONCLUSION: A supervised aerobic training program has the potential to alleviate persistent symptoms and improve exercise tolerance in patients with long COVID-19. Further research is necessary to confirm these effects in a large population. This intervention could be easily implemented in non-hospital settings, potentially benefiting a broader range of individuals. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT05961462. Registered on July 25, 2023.

A pilot cross-sectional investigation of symptom clusters and associations with patient-reported outcomes in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post COVID-19 Condition.

BACKGROUND: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is associated with long-term disability and poor quality of life (QoL). Cardinal ME/CFS symptoms (including post-exertional malaise, cognitive dysfunction and sleep disturbances) have been observed in Post COVID-19 Condition (PCC). To gain further insight into the potential role of ME/CFS as a post-COVID-19 sequela, this study investigates associations between symptoms and patient-reported outcomes, as well as symptom clusters. METHODS: Participants included Australian residents aged between 18 and 65 years formally diagnosed with ME/CFS fulfilling the Canadian or International Consensus Criteria or PCC meeting the World Health Organization case definition. Validated, self-administered questionnaires collected participants' sociodemographic and illness characteristics, symptoms, QoL and functional capacity. Associations between symptoms and patient-reported outcomes were investigated with multivariate linear regression models. Hierarchical cluster analysis was performed to identify symptom clusters. RESULTS: Most people with ME/CFS (pwME/CFS) and people with PCC (pwPCC) were female (n = 48/60, 80.0% and n = 19/30, 63.3%, respectively; p = 0.12). PwME/CFS were significantly younger (x̄=41.75, s = 12.91 years) than pwPCC (x̄=48.13, s =10.05 years; p =0.017). Autonomic symptoms (notably dyspnoea) were associated with poorer scores in most patient-reported outcome domains for both cohorts. None of the four symptom clusters identified were unique to ME/CFS or PCC. Clusters were largely delineated by the presence of gastrointestinal and neurosensory symptoms, illness duration, ME/CFS criteria met and total symptoms. CONCLUSIONS: Illness duration may explain differences in symptom burden between pwME/CFS and pwPCC. PCC diagnostic criteria must be refined to distinguish pwPCC at risk of long-term ME/CFS-like illness and subsequently deliver necessary care and support.

Post COVID-19 Condition (PCC), or Long COVID, refers to the ongoing symptoms experienced after acute COVID-19 illness. The symptoms reported by people with PCC (pwPCC) resemble Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). However, existing diagnostic criteria for PCC are broad and cannot discern PCC subtypes (such as pwPCC experiencing ME/CFS-like illness), which may require different approaches to care. This study contributes to improving PCC case criteria and approaches to care for both ME/CFS and PCC by investigating the relationships between symptoms and patient-reported outcomes among pwPCC and people with ME/CFS (pwME/CFS).For both cohorts, symptoms had a negative relationship with all aspects of health. Autonomic symptoms, notably breathing issues, returned the most negative associations. Pain, flu-like symptoms and lack of temperature control appeared more burdensome among pwPCC. These symptoms may signify the early stages of ME/CFS. Symptom clusters were also identified for the first time among a combined cohort of pwME/CFS and pwPCC in this study. Importantly, none of the symptom clusters were specific to ME/CFS or PCC. Instead, symptom clusters were defined by the prevalence of gastrointestinal and neurosensory symptoms, illness duration, ME/CFS criteria met and the total number of symptoms.This study suggests that the few differences between ME/CFS and PCC may be explained by illness duration. These findings further implicate ME/CFS as a potential post-COVID-19 outcome. As ME/CFS is associated with profound reductions in quality of life and functioning, identifying pwPCC experiencing ME/CFS-like illness through refined diagnostic criteria must be prioritised to ensure the delivery of necessary care.

Glucocorticoid treatment during COVID-19 infection: does it affect the incidence of long COVID?

BACKGROUND: Long COVID (LC) is a frequent complication of COVID infection. It usually results in cognitive impairment, myalgia, headache and fatigue. No effective treatment has been found yet. We aimed to explore the effect of glucocorticoid (GC) treatment during COVID-19 infection on the later development of LC. METHODS: We examined electronic health records from Clalit Health Services for documentation of COVID-19, GC treatment, and LC frequency. Background diagnoses, demographic data, hospitalization rates, and the use of anti-COVID drugs were recorded. RESULTS: 1,322,599 cases of COVID-19 infection met the inclusion criteria; 13,530 patients (1.02%) received GC treatment. 149,272 patients, 11.29% of COVID-19 patients were diagnosed with LC. Age and female gender were prognostic risk factors for LC (OR 1.06 for age, OR 1.4 for female gender; p value < 0.0001). Background psychiatric diagnoses, migraine, backache and irritable bowel syndrome were predisposing conditions for LC (OR 2.7, p value < .0001). Higher BMI was associated with a greater probability of LC (OR of 1.25 for obese population). COVID patients who received GC were diagnosed with LC more frequently: 2294 cases (16.95%) compared to 146,978 cases (11.23%) in the non-GC group; (adjusted OR of 1.28 ± 0.07, 95% CI, p < 0.0001). CONCLUSIONS: GC treatment during COVID-19 is correlated with the development of LC. In vivo and animal models may be used to explore the mechanism of this correlation. Future directions include prospective studies as well.

The persistence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) after SARS-CoV-2 infection: A systematic review and meta-analysis.

OBJECTIVES: Long COVID-19 (LC) patients experience a number of chronic idiopathic symptoms that are highly similar to those of post-viral Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). We have therefore performed a systematic review and meta-analysis to determine the proportion of LC patients that satisfy ME/CFS diagnostic criteria. METHODS: Clinical studies published between January 2020 to May 2023 were identified using the PubMed, Web of Science, Embase and CINAHL databases. Publication inclusion/exclusion criteria were formulated using the global CoCoPop framework. Data were pooled using a random-effects model with a restricted maximum-likelihood estimator. Study quality was assessed using the Joanna Briggs Institute critical assessment tool. RESULTS: We identified 13 eligible studies that reported a total of 1,973 LC patients. Our meta-analysis indicated that 51% (95% CI, 42%-60%) of LC patients satisfied ME/CFS diagnostic criteria with fatigue, sleep disruption, and muscle/joint pain being the most common symptoms. Importantly, LC patients also experienced the ME/CFS hallmark symptom, post-exertional malaise. CONCLUSIONS: Our study not only demonstrates that LC patients exhibit similar symptom clusters to ME/CFS, but that approximately half of LC patients satisfy a diagnosis of ME/CFS. Our findings suggest that current ME/CFS criteria could be adapted to the identification of a subset of LC patients that may facilitate the standardized diagnosis, management and the recruitment for clinical studies in the future. DATA AVAILABILITY: Data available upon request.

Disrupted Candidacy: A Longitudinal Examination of the Constrained Healthcare-Access Journeys of National Health Service Workers in Scotland Seeking Supports for Long COVID Illness.

INTRODUCTION: Evidence examines how persons experiencing Long COVID (LC) struggle to secure healthcare for symptoms. However, few studies examine healthcare workers experiencing LC, nor the complex and multiple difficulties faced when seeking and receiving healthcare. METHODS: This study is based on two phases of longitudinally conducted qualitative interviews, 6 months apart, with National Health Service (NHS) workers experiencing LC, from different occupational roles at NHS locales in Scotland (first interviews, n = 50; second interviews, n = 44). RESULTS: Multiple factors restricted healthcare access, including worries about pressuring the NHS and concerns over LC being legitimised. When healthcare was sought, workers struggled to secure support, referrals and treatment. The following reasons were included: (1) context: the restrictive pandemic healthcare context; (2) illness climate: low GP knowledge surrounding LC and how this could be treated, trends for ascribing symptoms to other causes and reluctance to diagnose LC; (3) sense-making of LC: healthcare availability linked to occupational role identity. To visualise and examine healthcare barriers, candidacy theory is applied, drawing inferences between healthcare context, illness climate, sense-making and identities. CONCLUSION: NHS workers' complex journeys represent Disrupted Candidacy, intersecting challenges across candidacy domains, restricting the seeking and receiving of LC healthcare. Findings provide insights into why NHS workers resisted and withdrew from healthcare-seeking, and the barriers they faced when attempting to secure LC support. This study presents a pathway for future LC illness research to use a modified candidacy theory framework. PATIENT AND PUBLIC CONTRIBUTION: This research focuses on amplifying and learning from lived experiences, and the voices of NHS workers in Scotland experiencing LC. Interviews represent primary data for this study; thus, participants and their healthcare journeys are centred in this research and all aspects of production, reporting and output. Explicit discussions of stakeholder group involvement are highlighted in the methods section.

Long COVID and Health Inequalities: What's Next for Research and Policy Advocacy?

INTRODUCTION: Organised by the 'Qualitative Long Covid Network', a workshop for qualitative Long COVID (LC) researchers, LC charity representatives and people with LC took place in June 2023, where research on the intersectional inequalities affecting LC prevalence, recognition and care was shared and discussed. METHODS: Five key themes were drawn up from presentations, discussions and reflections during the workshop, which are presented in this study. RESULTS: The following five themes are discussed: the unfairness of LC, difficulties in accessing care, mistrust of the healthcare system, a lack of understanding of LC and experiences of stigma and discrimination. Factors that widen or narrow inequalities related to LC were identified. CONCLUSION: A call to action is proposed to investigate and address inequalities through a robust LC research agenda that speaks with conviction to policy and decision-makers. We argue that there needs to be a strong investment in research and evidence-based policy and practice to mitigate the worst effects of the condition and address the inequalities in experience, treatment and support, which are experienced more often and more acutely by some of society's most vulnerable and disadvantaged individuals. PATIENT AND PUBLIC (PPI) CONTRIBUTION: Projects included in this article had PPI ongoing activity to inform their research. A member of the CONVALESCENCE PPI group presented at the QLC Network 'Long Covid and Health Inequalities' workshop, as did members of Long COVID Kids, Long COVID Support and Long COVID SOS charities. They were all invited to be co-authors of this article.

A call from patient-researchers to advance research on long COVID.

Long COVID is a chronic and often disabling illness with long-term consequences. Although progress has been made in the clinical characterization of long COVID, no approved treatments exist and disconnects between patients and researchers threaten to hinder future progress. Incorporating patients as active collaborators in long COVID research can bridge the gap and accelerate progress toward treatments and cures.

Facilitators and barriers of long-term exercise adherence in healthcare workers formerly suffering from post-COVID-19 syndrome : A qualitative 1-year follow-up and quantitative pilot study of the COFIT trial.

BACKGROUND: Early exercise intervention studies showed promising positive effects of physical exercising on post-COVID-19 symptoms; however, little is known about long-term training adherence and what influences it. MATERIAL AND METHODS: Semi-structured interviews were conducted with 17 participants of the 8­week original exercise intervention study. Facilitators and barriers were identified via thematic analysis and compared between those participants who continued their regular exercise behavior (continuous exercise group, CEG, n = 7) and those who stopped exercising (discontinuous exercise group, DEG, n = 10). Physical performance parameters and questionnaires regarding psychological health dimensions and work ability were assessed analogously to the original study. RESULTS: Qualitative analysis showed that two of the top three facilitators, (improving physical and mental health, sport has high priority) were the same in both groups. The respective third of the top three facilitators was (re)build physical and cognitive performance in the CEG and training in the group in the DEG. The top three barriers (exhaustion, sport has little priority, procrastination) were not only the same in both groups but also in the same order. CONCLUSION: The strongest post-COVID-19 associated facilitator for long-term exercise adherence is when the need for further reconditioning is felt. The strongest post-COVID-19 associated barrier is exhaustion. Availability of exercising in a group is a key factor in increasing long-term exercise adherence.

Impact of SARS-CoV-2 viral load on restrictive spirometry patterns in mild COVID-19 recovered middle-aged individuals: a six-month prospective study.

BACKGROUND: Long term respiratory complications of Corona Virus Disease-2019 (COVID-19) are of great concern. Many studies have reported altered respiratory patterns in COVID-19 recovered individuals and most of them were from severe to critically ill patients. The association of viral load at the time of infection with symptoms of long COVID-19 specifically on pulmonary functions after months of recovery is still not known. This study was aimed to assess the impact of SARS-CoV-2 viral load during mild-moderate COVID-19 disease on pulmonary functions in middle-aged population after 6-8 months of acute infection. METHODS: This study included 300 (102 healthy controls and 198 COVID-19 recovered) individuals between age 30-60 of either gender. Mild-moderate COVID-19 recovered individuals were recruited between a period of 6-8 months post-acute infection. Spirometry was performed with MIR-Spirolab-III. The association of spirometry pattern was compared with SARS-CoV-2 viral loads during acute infection. RESULTS: We observed up to 70% of the participants presented with either shortness of breath (11.5%), body aches (23.5%), recurrent cough (4.4%), recurrent respiratory infections (9.5%) and/or fatigue (33.3%) at follow up. In our study, 35.5% of COVID-19 recovered individuals had abnormal respiratory patterns (33.5% had restrictive and 2% had obstructive patterns). Viral load ≤ 20 CT value was associated with restrictive respiratory patterns (p = 0.004). No association was found between viral load and disease severity (p = 0.23). CONCLUSION: In this study, we found one third of mild-moderate COVID-19 recovered individuals have restrictive respiratory patterns after 6-8 months of recovery. These findings had a strong association with SARS-CoV-2 viral loads during acute infection which has been reported for the first time in our study. Studying the relationship between viral load and pulmonary functions can contribute to identifying potential risk factors for long COVID and developing preventive measures to mitigate the long-term impact on lung health. CLINICAL TRIAL NUMBER: Not applicable.

Cardiology Consult for the General Pediatrician after Cardiac Manifestations from a SARS-CoV-2 Infection.

The novel Coronavirus Disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, created a need for evidence-based guidelines for the evaluation, management, and follow-up after infection. Data have become rapidly available, creating a challenge for medical providers to stay abreast of the ever-evolving recommendations. This document, written collaboratively by pediatric cardiovascular experts, pediatricians, and sports medicine specialists, is focused on SARS-- CoV-2-related pediatric cardiac manifestations. It aims to provide a systemic review of high-yield literature related to all cardiovascular entities as a tool for primary pediatric clinicians to utilize as they consider the cardiac consequences of acute SARS-CoV-2 infection, MIS-C, vaccine-related myocarditis, return-to-play, and long COVID-19 syndrome.

Emergency department utilization among children with Long COVID symptoms: a COVID-19 research consortium study.

BACKGROUND AND OBJECTIVES: Long COVID, characterized by persistent symptoms beyond the acute infection phase, remains poorly characterized in children. Our study aim is to determine if children who exhibit any symptoms/conditions associated with Long COVID after acute COVID-19 infection have higher Emergency Department (ED) utilization compared to those who do not exhibit these symptoms. METHODS: Data from the HealthJump ambulatory database from the COVID-19 Research Database Consortium was utilized to identify pediatric COVID-19 cases from March 2020 to May 2023. Long COVID cases were defined based on symptoms/conditions occurring 30-180 days after initial COVID diagnosis. Descriptive statistics and multivariable logistic regression models were used to model the relationship between Long COVID and child ED utilization. RESULTS: Out of 130,010 children diagnosed with COVID-19, 43,645 (33.6%) exhibited at least one Long COVID symptom/condition. Children with Long COVID symptoms/conditions had 152% higher odds (OR: 2.52, CI: 2.32-2.73) of ED visits, while those with specific symptoms including "chest pain" had 255% higher odds (AOR: 3.55, CI: 2.73-4.54) and "fluid and electrolyte disturbances" had 229% higher odds (AOR: 3.29, CI: 2.23-4.73) compared to those without those symptoms/conditions. CONCLUSION: This study reveals that children with Long COVID symptoms had notably higher odds of ED visits, with chest pain, fluid imbalances, and generalized pain being most closely linked to such visits. This study highlights the burden of Long COVID on ED providers and underscores the importance of improved guidance for managing Long COVID symptoms in children.

Knowledge, Attitudes, and Practices Among Community Populations Toward Long COVID in China.

Purpose: This study aimed to assess the knowledge, attitudes and practices (KAP) among community populations toward Long COVID. Patients and Methods: This cross-sectional study was conducted between March 2023 and June 2023 at the Ordos Mongolian hospital and Ordos Central Hospital in Ordos, Inner Mongolia, China, employing a self-designed questionnaire to collect demographic data from community populations and evaluate their knowledge, attitudes, and practices toward Long COVID. Results: A total of 591 participants were enrolled in this study. Among them, 343 (58.04%) were female and 317 (53.64%) aged 40 to 59 years. The mean knowledge, attitudes and practices scores were 6.02±1.19 (possible range: 0-7), 26.83±2.96 (possible range: 7-35), and 45.91±7.20 (possible range: 11-55), respectively. The Pearson's correlation analysis indicated significant positive correlations between knowledge and attitudes (r=0.210, P<0.001), and attitudes and practices (r=0.476, P<0.001). The structural equation model demonstrated that knowledge positively affect attitudes, as indicated by a path coefficient of 1.028 (P<0.001), and attitudes positively affect practices, with a path coefficient of 0.817 (P<0.001). Conclusion: Although our findings indicate that community populations generally have adequate knowledge, active attitudes, and proactive practices regarding Long COVID, there is still a need for healthcare providers to further enhance Long COVID awareness in the community. This involves fostering positive attitudes through open communication, emphasizing the importance of early intervention and treatment adherence, and encouraging continued adherence to preventive measures.

Comparing personality traits of healthcare workers with and without long COVID: Cross-sectional study.

Aim: Pathological mechanisms of "long COVID" after recovery from the main symptoms of COVID-19 are unclear. We compared psychological differences between individuals with and without long COVID symptoms after initial COVID-19 infections. Methods: This study includes medical workers with and without history of COVID-19. We assessed the degree of depression, health-related quality of life (HRQOL), the degree of anxiety and fear of COVID-19, and we used an original questionnaire. In the COVID-19 group, we also assessed personality traits and anxiety. The COVID-19 group was subclassified into those with and without long COVID to examine differences in circumstantial and psychological examinations. Results: Of 310 participants (141 men, 169 women, median age: 40 years), 167 had history of COVID-19 (83/84, 37 years) and 143 did not (58 men/85 women, 46 years). In the COVID-19 group, 26 had long COVID (12/14, 32 years) and 141 did not (58/85, 46 years). Fewer participants in the COVID-19 group had had COVID-19 vaccinations. The long COVID group had higher number of symptoms at the time of illness and higher NEO Five Factor Inventory Neuroticism scores than the non-long COVID group. They also had poorer mental health according to HRQOL than those without. Conclusion: Risk factors for long COVID may include the number of symptoms at the time of illness and neurotic tendency on NEO Five Factor Inventory. Participants with long COVID had poorer mental health according to HRQOL. People with long COVID might be especially sensitive to and pessimistic about the symptoms that interfere with their daily lives, resulting in certain cognitive and behavioral patterns. They may benefit from early psychiatric intervention.

Occupational and industry prevalence of new long-term symptoms within American Red Cross blood donors with and without history of SARS-CoV-2 infection.

PURPOSE: Limited information is known about the burden of Long COVID by occupation and industry. This study compares the occurrence of self-reported new long-term symptoms lasting 4 weeks or longer among blood donors with and without prior SARS-CoV-2 infection by occupation and industry. METHODS: The American Red Cross invited blood donors 18 years and older who donated during May 4-December 31, 2021 to participate in online surveys. New long-term symptoms lasting 4 weeks or longer were assessed by self-reported occurrence of any of 35 symptoms since March 2020. SARS-CoV-2 infection status was determined by serological testing and self-report. We describe the prevalence of new long-term symptoms by SARS-CoV-2 infection status. We calculate the difference in reported new long-term symptoms by SARS-CoV-2 infection status within occupation and industry categories. RESULTS: Data were collected from 27,907 employed adults - 9763 were previously infected and 18,234 were never infected with SARS-CoV-2. New long-term symptoms were more prevalent among those previously infected compared to the never-infected respondents (45% vs 24%, p < 0.05). Among all respondents, new long-term symptoms by occupation ranged from 26% (installation, maintenance, and repair) to 41% (healthcare support) and by industry ranged from 26% (mining) to 55% (accommodation and food services). New long-term neurological and other symptoms were commonly reported by those previously infected with SARS-CoV-2. DISCUSSION: New long-term symptoms are more prevalent among certain occupation and industry groups, which likely reflects differential exposure to SARS-CoV-2. These findings highlight potential need for workplace accommodations in a variety of occupational settings to address new long-term symptoms.

Effects of Sulfur Thermal Water inhalations in long-COVID syndrome: spa-centred, double-blinded, randomised case-control pilot study.

BACKGROUND: The long-COVID syndrome is characterised by a plethora of symptoms. Given its social and economic impact, many studies have stressed the urgency of proposing innovative strategies other than hospital settings. In this double-blind randomised case-control trial, we investigate the effects of sulfur thermal water inhalations, rich in H2S, compared to distilled water inhalations on symptoms, inflammatory markers, nasal microbiome in long-COVID patients. METHODS: 30 outpatients aged 18-75, with positive diagnosis for long-COVID were randomised in two groups undergoing 12 consecutive days of inhalations. The active Group (STW) received sulfur thermal water inhalations whereas the placebo group received inhalations of sterile distilled non-pyrogenic water (SDW). Each participant was tested prior treatment at day 1 (T0), after the inhalations at day 14 (T1) and at 3 months follow-up (T2). At each time point, blood tests, nasal swabs for microbiome sampling, pulmonary functionality tests (PFTs) and pro-inflammatory marker measure were performed. RESULTS: The scores obtained in the administered tests (6MWT, Borg score, and SGRQ) at T0, showed a significant variation in STW group, at T1 and T2. Serum cytokine levels and other inflammatory biomarkers reported a statistically significant decrease. Some specific parameters of PFT's showed ameliorations in STW group only. Changes in the STW nasopharyngeal microbiota composition were noticed, especially from T0 to T2. CONCLUSIONS: Inhalations of sulfur thermal water exerted objective and subjective improvements on subjects affected by long-COVID. Significant reduction of inflammatory markers, dyspnea scores and quantitative and qualitative changes in the nasopharyngeal microbiome were also assessed.

A review of intravenous immunoglobulin in the treatment of neuroimmune conditions, acute COVID-19 infection, and post-acute sequelae of COVID-19 Syndrome.

Intravenous immunoglobulin (IVIG) is an immunomodulatory therapy that has been studied in several neuroimmune conditions, such as Guillain-Barré Syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and multiple sclerosis. It has also been proposed as a potential treatment option for acute COVID-19 infection and post-acute sequelae of SARS-CoV-2 infection (PASC). IVIG is thought to function by providing the recipient with a pool of antibodies, which can, in turn, modulate immune responses through multiple mechanisms including neutralization of cytokines and autoantibodies, saturation of neonatal fragment crystallizable receptors, inhibition of complement activation, and regulation of T and B cell mediated inflammation. In acute COVID-19, studies have shown that early administration of IVIG and plasmapheresis in severe cases can reduce the need for mechanical ventilation, shorten ICU and hospital stays, and lower mortality. Similarly, in PASC, while research is still in early stages, IVIG has been shown to alleviate persistent symptoms in small patient cohorts. Furthermore, IVIG has shown benefits in another condition which has symptomatic overlap with PASC, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), though studies have yielded mixed results. It is important to note that IVIG can be associated with several potential adverse effects, such as anaphylaxis, headaches, thrombosis, liver enzyme elevations and renal complications. In addition, the high cost of IVIG can be a deterrent for payers and patients. This review provides a comprehensive update on the use of IVIG in multiple neuroimmune conditions, ME/CFS, acute COVID-19, and PASC, as well as covers its history, production, pricing, and mechanisms of action. We also identify key areas of future research, including the need to optimize the use of Ig product dosing, timing, and patient selection across conditions, particularly in the context of COVID-19 and PASC.

Protocol for a pilot study: Feasibility of a web-based platform to improve nutrition, mindfulness, and physical function in people living with Post COVID-19 condition (BLEND).

Individuals with Post COVID-19 condition (PCC), or long COVID, experience symptoms such as fatigue, muscle weakness, and psychological distress, including anxiety, depression, or sleep disorders that persist after recovery from COVID-19. These ongoing symptoms significantly compromise quality of life and diminish functional capacity and independence. Multimodal digital interventions targeting behavioural factors such as nutrition and mindfulness have shown promise in improving health outcomes of people with chronic health conditions and may be beneficial for those with PCC. The BLEND study (weB-based pLatform to improve nutrition, mindfulnEss, and physical function, in patients with loNg COVID) study is an 8-week pilot randomized controlled trial evaluating the feasibility of a digital wellness platform compared to usual care among individuals with PCC. The web-based wellness platform employed in this study, My Viva Plan (MVP)®, integrates a holistic, multicomponent approach to promote wellness. The intervention group receives access to the digital health platform for 8 weeks with encouragement for frequent interactions to improve dietary intake and mindfulness. The control group receives general content focusing on improvements in dietary intake and mindfulness. Assessments are conducted at baseline and week 8. The primary outcome is the feasibility of platform use. Secondary and exploratory outcomes include a between-group comparison of changes in body composition, nutritional status, quality of life, mindfulness, physical activity, and physical performance after 8 weeks. Findings of this study will inform the development of effective web-based wellness programs tailored for individuals with PCC to promote sustainable behavioural changes and improved health outcomes.