The post COVID-19 syndrome (PCS) is an emerging phenomenon worldwide with enormous socioeconomic impact. While many patients describe neuropsychiatric deficits, the symptoms are yet to be assessed and defined systematically. In this prospective cohort study, we report on the results of a neuropsychiatric consultation implemented in May 2021. A cohort of 105 consecutive patients with merely mild acute course of disease was identified by its high symptom load 6 months post infection using a standardized neurocognitive and psychiatric-psychosomatic assessment. In this cohort, we found a strong correlation between higher scores in questionnaires for fatigue (MFI-20), somatization (PHQ15) and depression (PHQ9) and worse functional outcome as measured by the post COVID functional scale (PCFS). In contrast, neurocognitive scales correlated with age, but not with PCFS. Standard laboratory and cardiopulmonary biomarkers did not differ between the group of patients with predominant neuropsychiatric symptoms and a control group of neuropsychiatrically unaffected PCS patients. Our study delineates a phenotype of PCS dominated by symptoms of fatigue, somatisation and depression. The strong association of psychiatric and psychosomatic symptoms with the PCFS warrants a systematic evaluation of psychosocial side effects of the pandemic itself and psychiatric comorbidities on the long-term outcome of patients with SARS-CoV-2 infection.

The post COVID-19 syndrome (PCS) is an emerging phenomenon worldwide with enormous socioeconomic impact. While many patients describe neuropsychiatric deficits, the symptoms are yet to be assessed and defined systematically. In this prospective cohort study, we report on the results of a neuropsychiatric consultation implemented in May 2021. A cohort of 105 consecutive patients with merely mild acute course of disease was identified by its high symptom load 6 months post infection using a standardized neurocognitive and psychiatric-psychosomatic assessment. In this cohort, we found a strong correlation between higher scores in questionnaires for fatigue (MFI-20), somatization (PHQ15) and depression (PHQ9) and worse functional outcome as measured by the post COVID functional scale (PCFS). In contrast, neurocognitive scales correlated with age, but not with PCFS. Standard laboratory and cardiopulmonary biomarkers did not differ between the group of patients with predominant neuropsychiatric symptoms and a control group of neuropsychiatrically unaffected PCS patients. Our study delineates a phenotype of PCS dominated by symptoms of fatigue, somatisation and depression. The strong association of psychiatric and psychosomatic symptoms with the PCFS warrants a systematic evaluation of psychosocial side effects of the pandemic itself and psychiatric comorbidities on the long-term outcome of patients with SARS-CoV-2 infection.

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.

Objectif : La Covid-19 a conduit à de nombreuses complications. Parmi celles-ci, on compte le syndrome post-Covid-19, qui inclut fréquemment le malaise post-effort (MPE), observé dans environ 90% des cas. Après une analyse du profil sociodémographique des personnes atteintes de MPE, le présent mémoire a visé à comprendre ce phénomène en évaluant les différentes variables du MPE en fonction du niveau d'activité physique (AP) des personnes touchées. Méthodes : La collecte des données a été faite à l'aide d'un questionnaire mis en ligne sur Lime Survey et distribué via Facebook. Le questionnaire visait à évaluer le niveau d'AP (loisirs, travail et transport) avant et après l'infection par la Covid-19. La population ciblée pour cette étude était constituée de personnes ayant présenté le syndrome post-Covid-19, soit le MPE. Résultats : Globalement, les résultats indiquent que les individus avec MPE (n=154) sont moins actifs et plus sédentaires après avoir contracté la Covid-19 qu’avant. Toutefois, les analyses d’interactions ont permis de faire ressortir des éléments importants. Les personnes atteintes de MPE ont vu un maintien ou une diminution significative de l'AP au travail et totale (intensité moyenne et élevée) après avoir contracté la Covid-19. De façon plus spécifique, ce sont particulièrement les femmes et les personnes dont la dernière infection remonte à plus d'un an qui ont été touchées par cette baisse. Alors que des déplacements à pieds ont diminué chez les femmes, ils ont augmentés chez les hommes. Par ailleurs, les déplacements à vélo ont diminués après la Covid-19 et ce, plus particulièrement pour les hommes, indiquant un potentiel déplacements du vélo vers la marche pour le transport. Répondre positivement aux 5 questions sur le MPE était aussi associé à une plus grande réduction de l’AP d’intensité moyenne ainsi que moyenne et élevée au travail mais à une augmentation moins marquée de la sédentarité. Avoir une récupération plus lente était associée à une réduction plus importante de l’AP d’intensité moyenne à élevée au travail. Et alors que les individus non effrayés par la peur de faire un malaise post-effort augmentaient leur niveau d’AP (intensité moyenne et moyenne/élevée) au travail, ceux effrayés le réduisait à la suite de la Covid. Finalement, ni l’âge, ni le nombre de contaminations qu’ils ont subi et ni le lieu de naissance des répondants avec le MPE n’ont pas eu d’effet sur les changements du mode de vie. Conclusions : Cette étude révèle que les personnes atteintes du syndrome post-Covid-19 à risque de MPE sont non seulement plus sédentaires mais qu’elles rapportent une baisse de l'AP qui touche surtout le travail et ce, de façon plus prononcée chez les personnes gravement atteintes de MPE et chez les femmes. Ces résultats sont importants à considérer dans un contexte de la reprise d'AP au travail post-Covid-19 de ces patients qui peuvent avoir des niveaux de déconditionnement physique plus importants. / Objective: Covid-19 has led to numerous complications. Among these, we count the post-Covid-19 syndrome, which frequently includes post-exertional malaise (PEM), i.e., in about 90% of cases. After analyzing the sociodemographic profile of people with PEM, the current thesis aims to understand this phenomenon by evaluating the different variables of PEM according to the level of physical activity (PA). Methods: We collected data using an online questionnaire hosted on Lime Survey and distributed via Facebook. The questionnaire aimed to assess the level of PA (leisure, work, and transport) before and after Covid-19 infection. The target population for this study consisted of individuals who exhibited post-Covid-19 syndrome, also known as PEM. Results: Overall, the results indicate that individuals with PEM (n=154) are less active and more sedentary after contracting Covid-19 than before. However, interaction analyses have brought out some important elements. People suffering from MPE experienced either a maintenance or a significant decrease in PA at work and overall (medium and high intensity) after contracting Covid-19. More specifically, it was particularly women and people whose last infection was more than a year ago who were affected by this decrease. While walking decreased among women, it increased among men. Moreover, cycling decreased after Covid-19, especially among men, indicating a potential shift from cycling to walking for transportation. Responding positively to the 5 PEM questions was also associated with a greater reduction in medium-intensity PA and medium to high-intensity work, but with a less pronounced increase in sedentary behavior. Having a slower recovery was associated with a greater reduction in medium to high intensity PA at work. And while individuals not scared of PEM increased their level of PA (medium intensity and medium/high) at work, those scared reduced it following Covid. Finally, neither age, nor the number of infections they suffered, nor the birthplace of respondents with ME/CFS had an effect on lifestyle changes. Conclusions: This study reveals that individuals with post-Covid-19 syndrome at risk of PEM are not only more sedentary, but they also report a decrease in PA, primarily impacting work, and this is especially pronounced in those severely affected by PEM and in women. These findings are important to consider in the context of resuming PA at work post-Covid-19 for these patients who may have higher levels of physical deconditioning.