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Background: Up to 35% of people who have contracted the acute COVID-19 virus are experiencing prolonged symptoms, now known as Long COVID (LC)1. Our data supports that living with LC significantly impacts one’s physical health and cognition, thereby affecting one’s psychosocial well-being (social relationships, emotional wellness, and space/time for fun and joy (leisure)). Our research team worked collaboratively with LC stakeholders (e.g., people with long COVID (PLC), caregivers (CG), health and social care providers (HSCPs), insurance and disability workers, employers, members of the public) and patient-partners to co-design and develop an evidence- and experience-informed ‘LC Education and Awareness Hub’ (www.LivingWithLongCOVID.ca) that aims to address LC care needs across the continuum (i.e., acute, in/out-patient, community). Relevance and target audience: In alignment with ICIC’s pillars of integrated care, the relevance of this work in a global context will help advocate for LC population health needs by helping reduce health disparities, platform the voices of people with lived experience, and highlight the benefits of co-design methods to identify common goals and values. This work also has the potential to increase workforce capacity and capability through collaborative and integrated approaches across the care continuum. This project aims to leverage LC-specific resources and supports towards target audiences (i.e., provider-, patient-, caregiver-, and public-facing) to help optimize integrated rehabilitation supports. Methods: 26 key stakeholders (n=12 PWLC, n-4 CG and n=10 HSCPs) were recruited to participate in 8 virtual co-design2 workshops (May to July, 2023). Participants were engaged in a series of brainstorming, discussion, and consensus-building activities using personas and journey maps as tools for data collection. Outcome(s): Four key areas were identified as needing to be addressed within the ‘hub:’ (1) education, (2) advocacy and public health messaging, (3) health and social care reform and care integration, and (4) peer support. Our group also brainstormed meaningful knowledge translation outcomes that will be mobilized and disseminated into practice to better support all LC stakeholders. The ‘LC Education and Awareness Hub’ and KT outcomes will be digitally housed online (www.LivingWithLongCOVID.ca). Conclusion: This research can raise awareness of LC globally, identify the network of integrated support needed for LC care provision, and address the specific needs of all LC stakeholders involved across the continuum of care. In alignment with the ICIC24 conference theme, our person-centered and patient-integrated approaches to this project creates more potential for this work to ‘make integrated care a reality’ for people living with, or supporting someone with, LC.

Background: Up to 35% of people who have contracted the acute COVID-19 virus are experiencing prolonged symptoms, now known as Long COVID (LC)1. Our data supports that living with LC significantly impacts one’s physical health and cognition, thereby affecting one’s psychosocial well-being (social relationships, emotional wellness, and space/time for fun and joy (leisure)). Our research team worked collaboratively with LC stakeholders (e.g., people with long COVID (PLC), caregivers (CG), health and social care providers (HSCPs), insurance and disability workers, employers, members of the public) and patient-partners to co-design and develop an evidence- and experience-informed ‘LC Education and Awareness Hub’ (www.LivingWithLongCOVID.ca) that aims to address LC care needs across the continuum (i.e., acute, in/out-patient, community). Relevance and target audience: In alignment with ICIC’s pillars of integrated care, the relevance of this work in a global context will help advocate for LC population health needs by helping reduce health disparities, platform the voices of people with lived experience, and highlight the benefits of co-design methods to identify common goals and values. This work also has the potential to increase workforce capacity and capability through collaborative and integrated approaches across the care continuum. This project aims to leverage LC-specific resources and supports towards target audiences (i.e., provider-, patient-, caregiver-, and public-facing) to help optimize integrated rehabilitation supports. Methods: 26 key stakeholders (n=12 PWLC, n-4 CG and n=10 HSCPs) were recruited to participate in 8 virtual co-design2 workshops (May to July, 2023). Participants were engaged in a series of brainstorming, discussion, and consensus-building activities using personas and journey maps as tools for data collection. Outcome(s): Four key areas were identified as needing to be addressed within the ‘hub:’ (1) education, (2) advocacy and public health messaging, (3) health and social care reform and care integration, and (4) peer support. Our group also brainstormed meaningful knowledge translation outcomes that will be mobilized and disseminated into practice to better support all LC stakeholders. The ‘LC Education and Awareness Hub’ and KT outcomes will be digitally housed online (www.LivingWithLongCOVID.ca). Conclusion: This research can raise awareness of LC globally, identify the network of integrated support needed for LC care provision, and address the specific needs of all LC stakeholders involved across the continuum of care. In alignment with the ICIC24 conference theme, our person-centered and patient-integrated approaches to this project creates more potential for this work to ‘make integrated care a reality’ for people living with, or supporting someone with, LC.

Introduction and ObjectivesExisting evidence suggests there is an appetite for a structured maintenance programme following Covid rehabilitation to maintain functional ability.1 The objective of this study was to explore whether, three months on, this perception had changed, and whether maintenance warrants further exploration.MethodsCovid rehabilitation completers were invited for a face-to-face visit three months following discharge. During the visit, patients completed objective outcomes (previously reported2), and a semi-structured interview. Interviews, conducted by a research assistant were recorded and transcribed verbatim. Reflexive thematic analysis was conducted using NVivo (V1.6.1), and themes reviewed by two research team members who specialise in qualitative research.ResultsA total of 19 interviews were conducted (mean age 57.8±7 years; 79% white; 74% women).Three themes were generated (figure 1):1. I’ve got what I need to proceed (with caution)Participants felt they had progressed, had good understanding of their symptoms and how to manage them, and therefore had the confidence to proceed exercising with caution, taking into account their fatigue.2. I’ve found the onward path that works for meParticipants felt motivated to continue exercising in the way they had chosen. Individualised options were selected based on accessibility, what mattered to them, and how it worked alongside their own routine.3. I’ll return, if things changePatients felt symptoms had improved, but accepted they remained variable. They appreciated this may be the case and expressed appetite to return to rehabilitation should things change.Abstract P31 Figure 1Themes with illustrative quotes[Image Omitted. See PDF.]ConclusionDespite rehabilitation completers expressing an appetite for maintenance at point of discharge, three months later, most continued exercising independently, albeit with caution. Participants only felt they would need further input if there was a change to their symptoms, suggesting rehabilitation provided the skills and knowledge for effective onward self-management of Long Covid.ReferencesHouchen-Wolloff L, et al. An exploratory survey of maintenance option preferences for post-COVID patients following a rehabilitation programme [abstract]. Am. J. Respir. Crit. Care Med. 2023;207:A2168.Hong A, et al. ‘P28-Incremental and endurance shuttle walk test performance and functional assessment of chronic illness therapy fatigue scale are maintained or improved at 3-months following a 6-week in-person or online covid rehabilitation programme’. Thorax. 2023;78(Suppl 4), A123-A123.

This study aimed to identify plasma protein biomarkers for nutritional status as potential prognosticators of mortality in long-COVID-19, addressing the gap in understanding the disease's long-term cardiovascular risks and the role of immunity and nutrition in its progression. In this study, initially, 329 individuals were recruited, meeting the inclusion criteria, comprising 89 healthy controls, 186 patients with mild infection, and 54 with severe disease. Two months post-COVID, follow-up was conducted, categorizing patients into survivors (n=212) and non-survivors (n=28). 2-Dimensional Gel Electrophoresis (2DE) of plasma samples for protein separation was performed; after that, proteins were identified through LC-MS/MS. Mascot version 2.3.02 was followed by analysis using Samespots software 4.5.1 to calculate protein volume and area coverage. GraphPad Prism 5.0 was used for statistical analysis. LC-MS/MS confirmed Transthyretin (TTR) and serotransferrin (TF) as potential predictive biomarkers as the study found significant downregulation of TF and TTR in COVID-19 patients in comparison to healthy subjects, with a further decrease observed in severe cases compared to mild cases. Non-survivors also showed a significantly lower level. The study uncovered serum nutritional biomarkers capable of accurately predicting COVID-19 prognosis and long-COVID mortality due to cardiovascular complications, facilitating tailored nutritional care and guidance for individuals combating SARS-CoV-2. These findings underscore the significance of developing tailored nutritional protocols to enhance dietary practices, complemented by using probiotics and prebiotics, to manage COVID-19 and other infections.

Introduction As part of the recent international COVID Sleep Study-II, long COVID syndrome was found to be associated with chronic insomnia. However, an article submitted for publication out of the Hôpital Hôtel-Dieu found no significant difference between long-COVID-related insomnia and standard insomnia with respect to routine polysomnographic (PSG) parameters. In light of these findings, we seek to better understand the difference between long COVID insomnia and standard chronic insomnia by conducting a fractal analysis of the raw PSG signals of our subjects. Methods 15 long COVID patients with complaints of chronic insomnia were included as subjects, as well as 34 matched controls without long COVID who had similar complaints of chronic insomnia. All participants underwent one night of polysomnographic recording. We perform our analysis on movements of the abdomen (as an approximation of deep breathing quality) and on EEG waves, considering that shortness of breath and cognitive dysfunction are commonly associated with long COVID. Building upon an existing repertoire of medical research using the fractal dimension (FD) of patients’ signal data to differentiate pathologic and physiologic processes, we make use of Detrended Fluctuation Analysis (DFA) to calculate the FD of the abdomen (FDA) and of an aggregated EEG wave (FDE) for each patient. Results We find a decrease in the FDA (p=0.036) and increase in the FDE (p=0.012) of long COVID insomniacs with respect to those of our control group. These results are shown to be significant after applying a Holm-Bonferroni correction for multiple hypotheses. Conclusion Despite our small data sample, an in-depth analysis of PSG signals shows significant differences in the fractal nature of long-COVID-related insomnia with respect to standard chronic insomnia. Our results furthermore match our expectations, given that related research outside of the COVID domain indicates a decrease in the FD of muscle movements and an increase in the FD of EEG waves in unhealthy individuals. Further research could employ more participants in order to extend our results to other data channels outside of EEG signals and the abdomen. Support (if any)

Accumulating evidence points toward a very high prevalence of prolonged neurological symptoms among coronavirus disease 2019 (COVID-19) survivors. To date, there are no solidified criteria for ‘long-COVID’ diagnosis. Nevertheless, ‘long-COVID’ is conceptualized as a multi-organ disorder with a wide spectrum of clinical manifestations that may be indicative of underlying pulmonary, cardiovascular, endocrine, hematologic, renal, gastrointestinal, dermatologic, immunological, psychiatric, or neurological disease. Involvement of the central or peripheral nervous system is noted in more than one-third of patients with antecedent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, while an approximately threefold higher incidence of neurological symptoms is recorded in observational studies including patient-reported data. The most frequent neurological manifestations of ‘long-COVID’ encompass fatigue; ‘brain fog’; headache; cognitive impairment; sleep, mood, smell, or taste disorders; myalgias; sensorimotor deficits; and dysautonomia. Although very limited evidence exists to date on the pathophysiological mechanisms implicated in the manifestation of ‘long-COVID’, neuroinflammatory and oxidative stress processes are thought to prevail in propagating neurological ‘long-COVID’ sequelae. In this narrative review, we sought to present a comprehensive overview of our current understanding of clinical features, risk factors, and pathophysiological processes of neurological ‘long-COVID’ sequelae. Moreover, we propose diagnostic and therapeutic algorithms that may aid in the prompt recognition and management of underlying causes of neurological symptoms that persist beyond the resolution of acute COVID-19. Furthermore, as causal treatments for ‘long-COVID’ are currently unavailable, we propose therapeutic approaches for symptom-oriented management of neurological ‘long-COVID’ symptoms. In addition, we emphasize that collaborative research initiatives are urgently needed to expedite the development of preventive and therapeutic strategies for neurological ‘long-COVID’ sequelae.

Tim Nicholson is a Reader in Neuropsychiatry at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King’s College London where he leads the Neuropsychiatry Research and Education Group (NREG). He is an Honorary Consultant Neuropsychiatrist at the South London and Maudsley NHS Foundation Trust. His clinical and research work focuses on Functional Neurological Disorder (FND), immunopsychiatry and broader neuropsychiatric disorders – including those resulting from COVID-19.He set up a pioneering specialist multidisciplinary clinic for FND in 2012 and has over 20 years of experience working clinically with FND and it was the topic of his PhD and the majority of his subsequent research activity including leading on studies into mechanisms, outcome measures and novel treatments such as Transcranial Magnetic Stimulation (TMS) and more recently psychedelics and Virtual Reality. He has also led and been involved in research investigating autoimmune causes of psychiatric symptoms, such as OCD and psychosis, and been involved in work seeking to understand the extent and causes of both acute and chronic neurological and psychiatric complications of COVID-19. He currently works in a multidisciplinary team clinic for Long COVID at King’s College Hospital providing neuropsychiatric input.He is on the executive committee of the Neuropsychiatry faculty of the Royal College of Psychiatrist and the British Neuropsychiatry Association. He is secretary of the Fellowship of Postgraduate Medicine and chairs the MSc in Clinical Neuropsychiatry at the IoPPN. He is co-chair of the patient liaison committee of the FND Society, on the committee of the UK FND network and on the medical advisory board of FND Hope, FND Action and Long COVID Support.Functional Neurological Disorder (FND) is a complex disorder at the junction of neurology and psychiatry and therefore body and mind as well as physical and mental health. There are several key, potentially even unique, features of FND which pose particular challenges to selecting which outcomes (aspects of a disorder and it’s impacts) we should be measuring and then how we should measure these in both clinical services and research settings.There is increasing awareness of the critical importance of selecting the most meaningful outcomes and the optimal methods and instruments to measure them. It is also increasingly recognised that consensus is need on these choices to standardise and harmonise data so it can be optimally collated and compared, especially for clinical trials to accelerate the development of evidence based treatments. Furthermore it is critical that the perspectives of patients, carers, research funders and clinical service commissioners are involved in this consensus process to compliment those of clinical and research experts.In this talk I will give an overview of the unique challenges to measuring FND, the subtle complexities and importance of this topic and the currently recommended best options. I will also summarise current and planned research efforts in measuring FND and related disorders to provide some potential insights into how these recommendations might evolve in the coming years.

The association of SARS-CoV-2 variants with long-COVID symptoms is still scarce, but new data are appearing at a fast pace. This systematic review compares the prevalence of long-COVID symptoms according to relevant SARS-CoV-2 variants in COVID-19 survivors. The MEDLINE, CINAHL, PubMed, EMBASE and Web of Science databases, as well as the medRxiv and bioRxiv preprint servers, were searched up to 25 October 2022. Case-control and cohort studies analyzing the presence of post-COVID symptoms appearing after an acute SARS-CoV-2 infection by the Alpha (B.1.1.7), Delta (B.1.617.2) or Omicron (B.1.1.529/BA.1) variants were included. Methodological quality was assessed using the Newcastle–Ottawa Scale. From 430 studies identified, 5 peer-reviewed studies and 1 preprint met the inclusion criteria. The sample included 355 patients infected with the historical variant, 512 infected with the Alpha variant, 41,563 infected with the Delta variant, and 57,616 infected with the Omicron variant. The methodological quality of all studies was high. The prevalence of long-COVID was higher in individuals infected with the historical variant (50%) compared to those infected with the Alpha, Delta or Omicron variants. It seems that the prevalence of long-COVID in individuals infected with the Omicron variant is the smallest, but current data are heterogeneous, and long-term data have, at this stage, an obviously shorter follow-up compared with the earlier variants. Fatigue is the most prevalent long-COVID symptom in all SARS-CoV-2 variants, but pain is likewise prevalent. The available data suggest that the infection with the Omicron variant results in fewer long-COVID symptoms compared to previous variants; however, the small number of studies and the lack of the control of cofounders, e.g., reinfections or vaccine status, in some studies limit the generality of the results. It appears that individuals infected with the historical variant are more likely to develop long-COVID symptomatology.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection, the cause of coronavirus disease 2019 (COVID-19), is characterized by acute clinical pathologies, including various coagulopathies that may be accompanied by hypercoagulation and platelet hyperactivation. Recently, a new COVID-19 phenotype has been noted in patients after they have ostensibly recovered from acute COVID-19 symptoms. This new syndrome is commonly termed Long COVID/Post-Acute Sequelae of COVID-19 (PASC). Here we refer to it as Long COVID/PASC. Lingering symptoms persist for as much as 6 months (or longer) after acute infection, where COVID-19 survivors complain of recurring fatigue or muscle weakness, being out of breath, sleep difficulties, and anxiety or depression. Given that blood clots can block microcapillaries and thereby inhibit oxygen exchange, we here investigate if the lingering symptoms that individuals with Long COVID/PASC manifest might be due to the presence of persistent circulating plasma microclots that are resistant to fibrinolysis. Methods We use techniques including proteomics and fluorescence microscopy to study plasma samples from healthy individuals, individuals with Type 2 Diabetes Mellitus (T2DM), with acute COVID-19, and those with Long COVID/PASC symptoms. Results We show that plasma samples from Long COVID/PASC still contain large anomalous (amyloid) deposits (microclots). We also show that these microclots in both acute COVID-19 and Long COVID/PASC plasma samples are resistant to fibrinolysis (compared to plasma from controls and T2DM), even after trypsinisation. After a second trypsinization, the persistent pellet deposits (microclots) were solubilized. We detected various inflammatory molecules that are substantially increased in both the supernatant and trapped in the solubilized pellet deposits of acute COVID-19 and Long COVID/PASC, versus the equivalent volume of fully digested fluid of the control samples and T2DM. Of particular interest was a substantial increase in α(2)-antiplasmin (α2AP), various fibrinogen chains, as well as Serum Amyloid A (SAA) that were trapped in the solubilized fibrinolytic-resistant pellet deposits. Conclusions Clotting pathologies in both acute COVID-19 infection and in Long COVID/PASC might benefit from following a regime of continued anticlotting therapy to support the fibrinolytic system function.

La long covid syndrome è sempre più studiata e dibattuta. Cresce il numero delle pubblicazioni scientifiche, e i gruppi e le associazioni di pazienti affetti dalla sindrome sono sempre più attivi. C’è la preoccupazione che l’attenzione internazionale per questa sindrome potrebbe determinare un eccesso di procedimenti diagnostici e di interventi medici non necessari. D’altra parte, disponiamo di una robusta mole di evidenze di una costellazione di sintomi e disturbi sofferti dai pazienti guariti da covid-19. Affrontare questo problema significa dunque affrontare la coesistenza con covid-19 nel lungo periodo, annettendo questa patologia in una prospettiva di cronicità. La raccolta e l’analisi dei dati, dunque, potrebbero già permettere una stratificazione delle popolazioni a rischio, mettendo i servizi sociali nella condizione di rispondere in maniera adeguata alla domanda di assistenza, che si prevede possa pervenire da parte di un numero molto elevato di pazienti. Ma è essenziale che la real-world evidence vada di pari passo con la selezione, l’analisi e l’interpretazione delle informazioni raccolte nei database amministrativi, nei registri di malattia e nelle banche dati messe a punto da università e istituzioni per promuovere una sanità pubblica realmente personalizzata.