<p>  </p> <p>While evidence suggests that the mental health consequences of coronavirus disease 2019 (COVID-19) can persist for several months following infection, little is known about the longer-term mental health consequences and whether certain sociodemographic groups may be particularly impacted. The study objectives were to characterize the longer-term mental health consequences of COVID-19 infection and examine whether such consequences are more pronounced in Black people and people with lower socioeconomic status. 277 Black and White adults (age ≥ 30 years) with a history of COVID-19 (cases; tested positive ≥ 6 months prior to participation) or no history of COVID-19 infection (controls) completed a 45-minute online questionnaire battery. Unadjusted <em>t</em>-tests revealed that cases had greater depressive (<em>d</em> = 0.24), anxiety (<em>d</em> = 0.34), PTSD (<em>d</em> = 0.32), and insomnia (<em>d</em> = 0.31) symptoms than controls. These differences remained significant for symptoms of anxiety, PTSD, and insomnia after adjusting for age, sex, race, education, income, and smoking status. No case-control differences were detected for perceived stress and general psychopathology. Cases had more than double the odds of clinically significant symptoms of anxiety (<em>OR</em> = 2.22) and PTSD (<em>OR</em> = 2.40). Case-control status was more strongly and positively associated with depressive, anxiety, PTSD, perceived stress, and general psychopathology symptoms at lower education levels. Race and income were not moderators of the relationships. The mental health consequences of COVID-19 may be significant, widespread, and persist for at least 6 months after infection, and people with lower education levels may face a greater burden of these consequences.</p>

Acute Respiratory Distress Syndrome (ARDS) is common in COVID-19 patients and is associated with high mortality. The aim of this observational study was to describe patients’ characteristics and outcome, identifying potential risk factors for in-hospital mortality and for developing Long-COVID symptoms. This retrospective study included all patients with COVID-19 associated ARDS (cARDS) in the period from March 2020 to March 2021 who were invasively ventilated at the intensive care unit (ICU) of the University Hospital Dresden, Germany. Between October 2021 and December 2021 patients discharged alive (at minimum 6 months after hospital discharge—midterm survival) were contacted and interviewed about persistent symptoms possibly associated with COVID-19 as well as the quality of their lives using the EQ-5D-5L-questionnaire. Long-COVID was defined as the occurrence of one of the symptoms at least 6 months after discharge. Risk factors for mortality were assessed with Cox regression models and risk factors for developing Long-COVID symptoms by using relative risk (RR) regression. 184 Patients were included in this study (male: n = 134 (73%), median age 67 (range 25–92). All patients were diagnosed with ARDS according to the Berlin Definition. 89% of patients (n = 164) had severe ARDS (Horovitz-index < 100 mmHg). In 27% (n = 49) extracorporeal membrane oxygenation was necessary to maintain gas exchange. The median length of in-hospital stay was 19 days (range 1–60). ICU mortality was 51%, hospital mortality 59%. Midterm survival (median 11 months) was 83% (n = 55) and 78% (n = 43) of these patients presented Long-COVID symptoms with fatigue as the most common symptom (70%). Extreme obesity (BMI > 40 kg/m2) was the strongest predictor for in-hospital mortality (hazard ratio: 3.147, confidence interval 1.000–9.897) and for developing Long-COVID symptoms (RR 1.61, confidence interval 1.26–2.06). In-hospital mortality in severe cARDS patients was high, but > 80% of patients discharged alive survived the midterm observation period. Nonetheless, most patients developed Long-COVID symptoms. Extreme obesity with BMI > 40 kg/m2 was identified as independent risk factor for in-hospital mortality and for developing Long-COVID symptoms.

Indiana University-Purdue University Indianapolis (IUPUI) / While evidence suggests that the mental health consequences of coronavirus disease 2019 (COVID-19) can persist for several months following infection, little is known about the longer-term mental health consequences and whether certain sociodemographic groups may be particularly impacted. The study objectives were to characterize the longer-term mental health consequences of COVID-19 infection and examine whether such consequences are more pronounced in Black people and people with lower socioeconomic status. 277 Black and White adults (age ≥ 30 years) with a history of COVID-19 (cases; tested positive ≥ 6 months prior to participation) or no history of COVID-19 infection (controls) completed a 45-minute online questionnaire battery. Unadjusted t-tests revealed that cases had greater depressive (d = 0.24), anxiety (d = 0.34), PTSD (d = 0.32), and insomnia (d = 0.31) symptoms than controls. These differences remained significant for symptoms of anxiety, PTSD, and insomnia after adjusting for age, sex, race, education, income, and smoking status. No case-control differences were detected for perceived stress and general psychopathology. Cases had more than double the odds of clinically significant symptoms of anxiety (OR = 2.22) and PTSD (OR = 2.40). Case-control status was more strongly and positively associated with depressive, anxiety, PTSD, perceived stress, and general psychopathology symptoms at lower education levels. Race and income were not moderators of the relationships. The mental health consequences of COVID-19 may be significant, widespread, and persist for at least 6 months after infection, and people with lower education levels may face a greater burden of these consequences.

2025 / A reductionistic or silo approach lacks a whole-person approach in which all relevant body systems are assessed concurrently with the environment, contributing to gaps in understanding. Also, current person–environment occupational therapy models are not universally appropriate for diverse social contexts. The Advocate Human Capabilities (AHC) model is introduced to bridge this gap in care. The AHC model recognizes the person and the environment are inseparable from the molecular level to the ubiquitous level, with a cacophony of interactions between all body systems and multiple environmental factors. When there is high homeostasis at the molecular level and consonance at the ubiquitous level, persons are optimal with their capabilities. Capabilities lead to occupational choice, engagement, and well-being, which social and cultural determinants can positively or negatively impact. The AHC model is built on evidence-based literature from diverse fields, including neurology, psychology, and behavioral sciences. Western, Eastern, and Indigenous knowledge provides the foundation for the inclusive AHC model supporting diverse populations in Canada, the United States, and worldwide. The model provides a means to investigate why persons are not optimal in their desired occupations, strengthening person–environment interventions and supporting occupational choice and well-being. The AHC model applied to persons with Long COVID will be delivered to occupational therapists via an online workshop. The workshop begins with the current research outlining Long COVID symptoms, complications, population challenges, and current rehabilitation approaches, including the strengths and limitations of the World Health Organization’s rehabilitation guidelines. Workshop participants will be trained in the AHC model with robust supporting evidence. They will also learn how the AHC assessment method applies the AHC model, providing the tools to systematically assess person and environment factors simultaneously while establishing a timeframe individualized to the person’s symptoms and lived experience with Long COVID. Furthermore, participants will learn how to synthesize the information gained, leading to more targeted person–environment interventions from the micro to the macro level, including the nervous system, cognitive, mental health, and physical factors, all supporting occupational choice. The workshop is steeped in adult learning theory. It provides participants with multiple interactive learning experiences, enhancing their knowledge gain and ability to use and apply the model and approach to their occupational therapy practice. Participants will be voluntarily recruited to participate in program evaluation research at the workshop conclusion and 1 year later. The anonymous survey reflects participants’ perceptions regarding the utility and confidence of using the AHC model and whether using the AHC model will improve outcomes (person-identified goals). The developer will use the findings to further inform the AHC model’s development and workshop delivery methods. The AHC model is a new lens reflecting the complex, inseparable person–environment relationship. The AHC model strives to be culturally safe and relevant around the globe, respecting persons’ context, values, and beliefs. / 2026-12-13T00:00:00Z

No description available.

The intent of this thesis is to provide an in-depth overview of the neurological manifestations associated with long COVID. The review aimed to assess the cognitive functioning symptoms associated with SARS-CoV-2 post-infection (PASC), investigate the potential mechanisms by which SARS-CoV-2 affects the nervous system, contributing to cognitive fatigue, brain fog, and cognitive dysfunction, and explore the parallels between SARS-CoV-2 and Alzheimer’s Disease. Neuroinflammation emerges as a shared element among these mechanisms, significantly impacting cognitive function. The parallels between COVID-19 and Alzheimer's Disease offer insights into how Alzheimer's affects cognition, aiding in understanding COVID-19's impact. The review underscores a notable gender disparity: women exhibit a greater susceptibility to the adverse effects of COVID-19, yet research in this domain remains limited. It advocates for further investigation into sex-specific differences and emphasizes the importance of understanding and spreading awareness about long COVID's impact on neurocognitive function and the nervous system, given the tendency among many medical professionals to underestimate its significance.

This thesis examined the sensitivity of the EQ-5D-5L instrument in measuring health-related quality of life (HRQoL) among patients with persistent symptoms following COVID-19, including fatigue, memory and concentration problems, and dyspnea. Additionally, it was analyzed whether adding these symptoms to the EQ-5D-5L improved the explained variance for HRQoL. Patients from Uppsala University Hospital, Sweden, answered a survey that included questions on five dimensions of health represented by the EQ-5D-5L and an additional question on general health score called EQ-VAS. Multiple linear regression, Spearman’s rank correlation coefficient, and Least Absolute Shrinkage and Selection Operator (LASSO) were used to examine the sensitivity of the EQ-5D-5L. For the explanatory analysis, the Adjusted 𝑅2 was used to evaluate explanatory power with and without the presence of the symptoms. The results showed that the EQ-5D-5L dimensions explained a moderate proportion of the variance for fatigue and memory/concentration problems and a weak proportion for dyspnea. The explanatory analysis provided findings that fatigue significantly improved the explained variance of EQ-VAS by 5.5%, adding memory/concentration problems only improved it marginally, and adding dyspnea was non-significant. Additionally, strong to moderate correlations between fatigue and memory/concentration problems were found with multiple dimensions of the EQ-5D-5L. These findings suggest that the EQ-5D-5L instrument may be a valuable tool in assessing HRQoL in patients with persistent COVID-19 symptoms and that adding fatigue to the EQ-5D-5L could be beneficial for improving explanatory power to HRQoL in patients suffering from infectious disease. / COMBAT post-covid

Значительная доля людей, столкнувшихся с коронавирусной инфекцией имеют осложнение в виде COVID-19-ассоциированной пневмонии и нуждаются в доступной и квалифицированной реабилитации. Цель работы - оценить влияние программы физической реабилитации на толерантность к физическим нагрузкам и функциональное состояние кардио-респираторной системы пациентов, перенесших COVID-19-ассоциированную пневмонию. В исследовании приняли 20 пациентов, перенесших COVID-19-ассоциированную пневмонию. В работе использовались следующие методы исследования: оценка толерантности к физической нагрузке оценивалась с помощью теста шестиминутной ходьбы, для оценки степени одышки после нагрузки использовалась шкала Борга, определяли сатурацию в покое и после проведения теста шестиминутной ходьбы, оценивалась частота сердечных сокращений до и после тестирования, а также выраженность одышки при повседневной деятельности оценивалась по шкале mMRC. Согласно полученным результатам, разработанная программа реабилитации повлияла на повышение толерантности к физическим нагрузкам, улучшение функционального состояния кардио-респираторной системы и субъективной переносимости физической нагрузки у пациентов, перенесших COVID-19-ассоциированную пневмонию. / A significant proportion of people who have experienced coronavirus infection have a complication in the form of COVID-19-associated pneumonia and need affordable and qualified rehabilitation. The aim of the work was to evaluate the impact of the physical rehabilitation program on exercise tolerance and the functional state of the cardio-respiratory system in patients who had undergone COVID-19-associated pneumonia. The study included 20 patients with COVID-19-associated pneumonia. Research methods were used in the work: assessment of exercise tolerance was assessed using a six-minute walk test, the Borg scale was used to assess the degree of dyspnea after exercise, saturation was determined at rest and after a six-minute walk test, heart rate was assessed before and after testing, as well as the severity of dyspnea during daily activities was assessed using the mMRC scale. According to the results obtained, the developed rehabilitation program influenced the increase in exercise tolerance, the improvement of the functional state of the cardio-respiratory system and the subjective exercise tolerance in patients who underwent COVID-19-associated pneumonia.

Background: Post COVID-19 Condition (PCC, also known as long COVID and post-acute sequelae of COVID-19) is a major public health concern with severe and pervasive impacts on physical and mental health. PCC is highly heterogeneous and may manifest as different clusters of symptoms of varying intensity and duration. The etiology of PCC remains uncertain, though several underlying pathophysiological mechanisms, such as cellular damage, inflammatory cytokines, and a hypercoagulable state, are thought to contribute to PCC inception and trajectory. Examination of potential serological markers of PCC, accounting for clinical covariates, may yield emergent pathophysiological insights. Objectives: Primary objectives of this thesis are to 1) Identify key clinical and potential serological predictors of PCC; 2) Acquire clinical and serological data in a large-scale prospective observational study; 3) Assess relationships between PCC and serological markers, accounting for clinical covariates; 4) Systematically review evidence to date on primary observational studies comparing serological response between people with and without persistent symptoms post COVID-19 recovery; 5) Discuss persisting gaps in knowledge and data quality, and propose strategies for resolve. Methods: This thesis is framed around three core efforts: 1) The design of survey questions and study materials, recruitment of participants, and data collection in a large-scale prospective cohort study launched in 2020; 2) The assessment of relationships between pre-defined serological predictors and PCC, accounting for clinical covariates; and 3) A robust rapid review of PCC onset and phenotype as functions of serological markers. Expert opinion was sought to define serological predictors. Clinical predictors were defined a priori based on systematic reviews meeting AMSTAR 2 guidelines. Conclusions: To address objectives, we described efforts to collect clinical and serological data from a large-scale prospective cohort study; identify PCC-cases and infected-controls; assess associations between pre-defined serological predictors (IgG titres targeting SARS-CoV-2 spike (S), nucleocapsid (N), and receiver binding domain (RBD) antigens, and efficient neutralization) and PCC; and synthesized findings from an extensive rapid review on PCC as a function of serological markers. Our multivariate analysis using Stop the Spread Ottawa data is, to our knowledge, the first Canadian study to report the direction and magnitude of association between selected serological predictors (anti-IgG response to S, N, and RBD SARS-CoV-2 antigens, and neutralizing efficiency) and PCC status and impact on quality of life. Finally, we described five potential strategies which may improve the accessibility, quality, and amalgamation of data pertaining to PCC: 1) Fostering comparability between studies to enable synthesis of multiple datasets; 2) Advancing the characterization and consensus on PCC phenotypes; 3) Employing innovative modelling strategies that could potentially yield novel insights; 4) Promoting robust collaboration and knowledge sharing among research teams; and 5) Engaging people with lived experience at all stages of research.

L'encéphalomyélite myalgique (EM), communément appelée syndrome de fatigue chronique (SFC), est une maladie chronique complexe, impliquant divers facteurs biochimiques, métaboliques, génétiques et épigénétiques dans sa pathogenèse. L'EM se caractérise par une fatigue persistante et débilitante, un malaise post-effort (PEM), des douleurs, des troubles du sommeil, des troubles cognitifs et d'autres symptômes. L'EM constitue un problème de santé important, compte tenu de sa prévalence dans la population générale. Cependant, notre compréhension des origines de l’EM reste limitée; son diagnostic est difficile et il n’existe aucun traitement curatif définitif ni de biomarqueur officiellement approuvé. Les approches de prise en charge actuelles visent principalement à soulager les symptômes, soulignant le besoin urgent de mieux comprendre ses causes sous-jacentes. Le développement de l’EM est reconnu comme une confluence de prédispositions génétiques et d’expositions environnementales, compte tenu de l’hétérogénéité clinique de cette pathologie. Ces dernières années, de nombreuses voies étiologiques ont été suggérées, notamment un développement post-infectieux de l’EM, qui reste l’une des principales hypothèses. L'implication de mécanismes épigénétiques, principalement la méthylation de l'ADN, un régulateur bien documenté de l'expression des gènes, est également apparu comme un acteur essentiel dans la pathogenèse de l'EM. Il est intéressant de noter, et avec une note d’inquiétude, que près de deux ans après la pandémie de SRAS-CoV-2 à l’origine du COVID-19, une cohorte croissante d’individus auparavant en bonne santé souffre du Long COVID (LC), une manifestation de symptômes persistants provenant de l’infection initiale. Il est remarquable de constater qu’il existe un chevauchement évident entre les présentations cliniques de l’EM et de la LC. Cependant, les mécanismes qui sous-tendent ce chevauchement restent encore à élucider. Dans le cadre de cette thèse, je me suis intéressée dans un premier temps à identifier les changements épigénétiques associés à l'EM à partir de la salive. Le choix d’utiliser la salive représente une approche non-invasive et découle également du fait que des études précédentes ont mis en évidence que les profils de méthylation de l’ADN obtenu des cellules buccales présentes dans la salive étaient assez similaires aux profiles observés au niveau du cerveau et des muscles (des tissus difficilement accessibles mais pourtant atteints dans l’EM) comparativement aux cellules mononuclées du sang périphériques (PBMCs). Cette approche pourrait aider à établir une signature épigénétique susceptible de combler le fossé conceptuel entre la génétique et l'influence environnementale dans la pathogenèse de l'EM. En effet, les sites CpG/gènes identifiés avec une méthylation différentielle pourraient être impliqués dans des mécanismes physiopathologiques associés au développement et/ou à la gravité de l'EM. Après correction de Bonferroni, mes travaux ont révélé un seul site CpG, "cg19803194", différentiellement méthylé chez les patients atteints d'EM par rapport aux sujets sains appariés pour l’âge. Ce site CpG est situé dans le corps du gène PTPRN2 codant pour la tyrosine phosphatase receptor type N2. De plus, le gène PTPRN2 contient un microARN intronique, le miR-153-3p (miR-153-2), qui est corégulé avec son gène hôte. En raison des défis éthiques et logistiques liés à l'accès aux tissus cérébraux ou musculaires, nous avons mesuré les niveaux circulants en miR-153-3p dans le plasma comme mesure de substitution pour évaluer les fluctuations de l'expression de PTPRN2. Nous avons donc analysé ce miARN comme un proxy prometteur pour mieux comprendre la dynamique d’expression de PTPRN2. Notre stratification des patients atteints d'EM basée sur les niveaux de méthylation de l'ADN cg19803194 (hypo vs hyper) a révélé qu'une réduction des niveaux circulants du miR-153-3p a été observée dans le groupe hypo-méthylé, ce qui concorde avec de précédentes études montrant que l'hypométhylation au niveau du corps des gènes, entraine habituellement une diminution de leur transcription. Cependant, l’intrigue a été amplifiée par un schéma contre-intuitif observé chez un sous-ensemble de patients. Cette découverte inattendue, nous a incité à découvrir un mécanisme alternatif régissant la régulation des niveaux de miR-153-3p en circulation, qui implique de manière complexe une interaction dynamique des niveaux nucléaires de PHB2 (Prohibitine 2) dans le contrôle de la maturation de certains miARN dont le miR-153-3p. La LC est un trouble complexe avec des symptômes prolongés et hétérogènes qui s’apparentent avec l’EM. Dans le cadre de ma seconde étude, nous avons utilisé une manoeuvre de provocation standardisée pour induire un malaise post-effort (PEM), ce qui nous a permis de stratifier les patients LC en deux groupes : LC1 (sévère) et LC2 (léger à modéré) en fonction de la gravité du PEM. Les patients LC1 présentaient des scores de gravité de la maladie significativement plus élevés et des scores neurocognitifs plus mauvais que les patients classés dans le groupe LC2. Ceci était étroitement lié aux scores PEM élevés chez les patients LC1 et aux scores PEM réduits chez les patients LC2. Nous avons également utilisé le profilage de la méthylation de l'ADN des cellules mononucléées du sang périphérique (PBMC) pour étudier les changements dans la méthylation de l'ADN associés aux symptômes de la LC (n = 24) par rapport aux participants ayant eu la COVID-19, suivie d’une rémission complète (SC pour Short COVID en anglais) (n = 4). Il est intéressant de noter que nous avons identifié des altérations de plusieurs gènes impliqués dans le dysfonctionnement neurocognitif et le changement de la réponse immunitaire liés à la persistance des symptômes de la LC. En outre, dans le cadre de ma troisième étude, nous avons effectué une analyse complète de la méthylation de l'ADN à l'échelle du génome, à partir d'échantillons de salive provenant du même groupe de patients LC (n=24) LC, de 4 participants SC et de 13 témoins sains (HC) pré-pandémiques. Nous avons étudié les signatures épigénétiques associées à la LC. Nous avons constaté que les patients LC présentaient une hypométhylation significative de trois gènes communs, MEST, DDR1 et LRP1, par rapport aux participants SC et HC. Ces gènes sont impliqués dans la cascade de l’inflammation, l’altération de la réponse immunitaire et des maladies neurologiques. Nous avons également signalé des altérations de la méthylation de LGR6, ZFAND2A et TDG dans les PBMCs et la salive chez les mêmes individus associés à la sévérité de la LC. Plus précisément, nous avons constaté une hypométhylation au niveau des gènes LGR6 et ZFAND2A et une hyperméthylation au niveau du gène TDG dans les cas graves (groupe LC1) par rapport aux cas légers à modérés (groupe LC2). Cette convergence de profils entre la salive et les PBMCs souligne l'importance de LGR6, ZFAND2A et TDG dans la gravité des LC. L’ensemble des résultats obtenus dans le cadre de cette thèse apporte un éclairage nouveau et pertinent sur les mécanismes épigénétiques qui sous-tendent l’EM et la COVID longue. Les nouvelles connaissances présentées dans les trois manuscrits ci-joints devraient nous permettre de mieux comprendre l’EM et la COVID longue, de développer de futures stratégies diagnostiques, thérapeutiques et préventives, mais également de mieux gérer les effets à long terme de ces conditions. En effet, les altération épigénétiques identifiées dans ces deux contextes pathologiques, plus précisément au niveau de la méthylation de l’ADN, pourraient être impliquées dans la sévérité et la persistance des symptômes de ces pathologies complexes, distinctes et présentant tout de même des similitudes. / Myalgic encephalomyelitis (ME), also known as chronic fatigue syndrome (CFS), is a complex chronic disease involving various biochemical, metabolic, genetic, and epigenetic factors. Patients with ME experience persistent and debilitating fatigue, post-exertional malaise (PEM), pain, sleep disturbances, cognitive impairment, and other symptoms. ME is a significant health problem, with an estimated prevalence of 0.2% to 0.5% in the general population. However, our understanding of the origins of ME remains limited; its diagnosis is complex, and there is no definitive cure or officially approved biomarker. Current management approaches focus primarily on relieving symptoms, highlighting the urgent need to understand its underlying causes better. The development of ME is thought to be a confluence of genetic predispositions and environmental exposures. In recent years, many etiological pathways have been suggested, including a post-infectious development of ME, which remains one of the main hypotheses. The involvement of epigenetic mechanisms, primarily DNA methylation, a well-documented regulator of gene expression, has also emerged as a critical player in the pathogenesis of ME. Interestingly, and with a note of concern, nearly two years after the SARS-CoV-2 pandemic that caused COVID-19, a growing cohort of previously healthy individuals suffer from Long COVID (LC), a manifestation of persistent symptoms from the initial infection. Remarkably, there is a clear overlap between the clinical presentations of ME and LC. However, the mechanisms underlying this overlap remain to be elucidated. This thesis investigated the epigenetic mechanisms underlying ME and LC. As part of this thesis, I was initially interested in identifying the epigenetic changes associated with ME from saliva. Saliva is a non-invasive sample that can be easily collected, and previous studies have shown that the DNA methylation profiles obtained from buccal cells present in saliva are similar to those observed in the brain and muscles. This suggests that saliva could be used as a proxy for these tissues, which are difficult to access but are thought to be involved in the pathogenesis of ME. I used Bonferroni's correction to identify a single CpG site, "cg19803194", differentially methylated in ME patients compared to age-matched healthy subjects. This CpG site is located in the body of the PTPRN2 gene, which encodes the tyrosine phosphatase receptor type N2. The PTPRN2 gene also contains an intronic microRNA, miR-153-3p (miR-153-2), which is co-regulated with its host gene. Due to ethical and logistical challenges, I measured circulating levels of miR-153-3p in plasma as a surrogate measure to assess fluctuations in PTPRN2 expression. This miRNA is a promising proxy for understanding the expression dynamics of PTPRN2 because it is located in the same gene and is co-regulated with it. My stratification of ME patients based on cg19803194 DNA methylation levels (hypo vs hyper) revealed that a reduction in circulating levels of miR-153-3p was observed in the hypo-methylated group. These findings agree with previous studies showing that hypomethylation in the body of genes usually decreases their transcription. However, a counterintuitive pattern was observed in a subset of patients. This unexpected finding prompted me to discover an alternative mechanism governing the regulation of circulating miR-153-3p levels. This mechanism involves a dynamic interaction of nuclear PHB2 (Prohibitin 2) levels in controlling the maturation of certain miRNAs, including miR-153-3p. LC is a complex disorder with prolonged and heterogeneous symptoms that resemble myalgic encephalomyelitis (ME). In my second study, we used a standardized provocative maneuver to induce post-exertional sickness (PEM), which allowed us to stratify LC patients into two groups: LC1 (severe) and LC2 (mild to moderate), depending on the severity of the PEM. LC1 patients had significantly higher disease severity scores and worse neurocognitive scores than patients classified in the LC2 group. This was closely related to high PEM scores in LC1 patients and reduced PEM scores in LC2 patients. We also used peripheral blood mononuclear cell (PBMC) DNA methylation profiling to investigate changes in DNA methylation associated with LC symptoms (n=24) compared to participants who had COVID followed by complete remission Short COVID (SC) (n = 4). Interestingly, we identified alterations in several genes implicated in neurocognitive dysfunction and changes in immune response related to the persistence of LC symptoms. In my third study, we also performed a comprehensive genome-wide DNA methylation analysis of saliva samples from the same group of LC patients (n=24), 4 SC participants, and 13 pre-pandemic healthy controls (HC). We studied the epigenetic signatures associated with LC. We found that LC patients showed significant hypomethylation of three common genes, MEST, DDR1, and LRP1, compared to SC and HC participants. These genes are involved in the cascade of inflammation, impaired immune response, and neurological disease. We also reported LGR6, ZFAND2A, and TDG methylation alterations in PBMCs and saliva in the same individuals associated with CL severity. Specifically, we found hypomethylation at the LGR6 and ZFAND2A genes and hypermethylation at the TDG gene in severe cases (LC1 group) compared to mild to moderate cases (LC2 group). This convergence of profiles between saliva and PBMCs highlights the importance of LGR6, ZFAND2A, and TDG in the severity of CL. All the results obtained in this thesis shed new and relevant light on the epigenetic mechanisms underlying ME and LC. The new knowledge in the three attached manuscripts allowed us to understand ME and LC better, develop future diagnostic, therapeutic, and preventive strategies, and better manage these conditions' long-term effects. Epigenetic alterations, more precisely at the level of DNA methylation, have been identified in both ME and long-term COVID. These alterations could be involved in the severity and persistence of the symptoms of these complex pathologies, which are distinct but share some similarities. The findings of this thesis suggest that epigenetics could be a promising target for developing new treatments for ME and long-term COVID. Further research is needed to confirm these findings and to develop effective therapeutic interventions.