ACKNOWLEDGEMENTS I would like to take this moment to extend my utmost appreciation for all the support provided by my supervisor, Dr. Russell de Souza. He assisted me along the way and ensured that I was always on the right path to achieve all my goals and checkpoints in every circumstance. I would also like to thank my committee for providing me with fantastic support: Ms. Laura Banfield for always being there to help solve any problem in this process, and Dr. Zain Chagla for providing a plethora of knowledge from the technical perspective of infectious disease and being so patient. Special thanks to Dr. Alexandra Mayhew for her support in our prevalence meta-analysis. Finally, I would like to thank my family, my wife, Dr. Sanjida Rowshan Anannya, for whom I am here today, and my parents, siblings, and in-laws; you are always there for me in every walk of life. You are why I have gotten to where I am today and are my daily inspiration. / Background: Bacteria is a major cause of many infectious diseases, and the treatment for these diseases is antibiotics designed to kill or subdue the growth of the bacteria. However, bacteria evolve, and if an antibiotic prescription is not the right antibiotic for the right patient at the right time with the correct dose and the right route, Antimicrobial Resistance (AMR) may result. During this pandemic, the use of antibiotics to treat hospitalized COVID-19 patients without any bacterial coinfection threatens the effectiveness of antibiotic treatment for current and future bacterial infections. Methods: A systematic search was conducted of the Embase, Medline, Web of Science, and Cochrane Library databases by generating search terms using the concepts of “COVID-19,” “Bacterial Coinfection,” “Secondary bacterial infection,” and “Antimicrobial resistance” to identify studies that reported the prevalence of antibiotic prescription for the treatment of COVID-19 in hospitalized patients with and without bacterial coinfection. The pooled estimate of the percentage of the total and confirmed appropriate antibiotic prescriptions provided to hospitalized COVID-19 patients was generated using a random effect meta-analysis with inverse variance weighting. Result: Of 157,623 participants from 29 studies included in our review, 67% (CI 64% to 71%, P<0.00001) were prescribed antibiotics, among which 80% (CI 76% to 83%, P<0.00001) prescriptions were given for the COVID-19 patients without any bacterial coinfections. The use of antibiotics varied during the pre-immunosuppressive period (before 16 June 2020) and post-immunosuppressive period of the pandemic and between the High-Income Countries and Upper and Lower Middle-Income Countries. Conclusion: This Systematic Review and Meta-analysis finds greater than expected use of antibiotics to treat hospitalized COVID-19 patients without bacterial coinfections, which can worsen AMR globally. Clear and concrete guidelines for the use of antibiotic prescriptions to treat COVID-19 patients, strict monitoring, and compliance with Antimicrobial Stewardship are needed to prevent over-prescription. / Thesis / Master in Advanced Studies (MAS) / Bacteria is a major cause of many infectious diseases. Before the discovery of Antibiotics in 1928, hundreds of thousands of people used to die due to infectious diseases caused by bacteria. While Antibiotics are essential to treat bacterial infectious diseases, overuse or misuse can accelerate Antibiotic Resistance, a phenomenon when bacteria change and/or develop the ability to escape the drugs designed to kill them. Self-medication, availability of antibiotics without a prescription, and inappropriate dosing of antibiotics can worsen the situation. During the COVID-19 pandemic, antibiotics were commonly prescribed as part of the treatment regime for COVID-19, even when a clear bacterial infection was not identified. In our Systematic Review and Meta-analysis, we aimed to see the frequency of antibiotic prescriptions to treat hospitalized COVID-19 patients without any bacterial coinfections.

No description available.

Our objective was to analyze longitudinal cellular and humoral immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in people with multiple sclerosis (pwMS) on B-cell depleting treatment (BCDT) compared to pwMS without immunotherapy. We further evaluated the impact of COVID-19 infection and vaccination timing. PwMS (n = 439) on BCDT (ocrelizumab, rituximab, ofatumumab) or without immunotherapy were recruited for this prospective cohort study between June 2021 and June 2022. SARS-CoV-2 spike-specific antibodies and interferon- release of CD4 and CD8 T-cells upon stimulation with spike protein peptide pools were analyzed at different timepoints (after primary vaccination, 3 and 6 months after primary vaccination, after booster vaccination, 3 months after booster). Humoral response to SARS-CoV-2 was consistently lower whereas T-cell response was higher in patients with BCDT compared to controls. Cellular and humoral responses decreased over time after primary vaccination and increased again upon booster vaccination, with significantly higher antibody titers after booster than after primary vaccination in both untreated and B-cell-depleted pwMS. COVID-19 infection further led to a significant increase in SARS-CoV-2-specific responses. Despite attenuated B-cell responses, a third vaccination for patients with BCDT seems recommendable, since at least partial protection can be expected from the strong T-cell response. Moreover, our data show that an assessment of T-cell responses may be helpful in B-cell-depleted patients to evaluate the efficacy of SARS-CoV-2 vaccination.

El virus SARS-CoV-2 que origina la infección respiratoria conocida como COVID-19, puede afectar a múltiples órganos y sistemas y generar diversas complicaciones, así como provocar síntomas persistentes más allá de la fase aguda. El pulmón es el órgano primario de afectación de la enfermedad y todavía hoy se desconoce la capacidad de recuperación pulmonar tras la infección por SARS-CoV-2. Los primeros datos contemplaban un porcentaje elevado de secuelas pulmonares tras la neumonía, no obstante, otros acercamientos más recientes a la enfermedad resultan más alentadores y evidencian que la trascendencia a largo plazo puede ser menor con alteraciones pulmonares residuales un año después del diagnóstico inicial entre el 2% y 24% de los casos. A pesar de ello, todas estas condiciones han provocado que en los supervivientes de la infección se constante una peor Calidad de Vida Relacionada con la Salud (CVRS). Generalmente, las peores puntuaciones se obtienen en la fase aguda, es decir, durante el primer mes después del diagnóstico, pero perduran en el tiempo y se pueden constatar tras varios meses (6 meses) después de la infección. No existe uniformidad en cuanto a los aspectos de la CVRS más afectados por la enfermedad y parece variar en el tiempo. Los síntomas persistentes y algunos factores como el género femenino, la edad avanzada, la necesidad de ingreso hospitalario o ingreso en UCI, el estatus social bajo o enfermedades como la diabetes mellitus o la insuficiencia cardiaca se han asociado con peores puntuaciones en la CVRS en estudios previos. El objetivo de esta tesis doctoral consiste en analizar el estado de salud y la Calidad de Vida Relacionada con la Salud en pacientes que han superado una neumonía por COVID-19. Además, también tiene como objetivos específicos examinar su evolución, evaluar el impacto que las secuelas pulmonares post-COVID-19 tienen en la Calidad de Vida Relacionada con la Salud e identificar la influencia del género en la Calidad de Vida Relacionada con la Salud en pacientes que han desarrollado secuelas pulmonares tras la infección por SARS-CoV-2. Todo ello para, en última instancia, intentar aumentar los conocimientos sobre la enfermedad y con ello mejorar la calidad de la asistencia a los pacientes afectados por COVID-19. Con este propósito se ha diseñado un estudio observacional prospectivo de pacientes supervivientes a neumonía por SARS-CoV-2, entre febrero y mayo de 2020. Se ha realizado una evaluación a los 3 y 12 meses del inicio de la enfermedad de cada paciente. Los datos se han obtenido mediante la revisión de la historia clínica y la realización a los pacientes de una exploración física, pruebas de imagen como una radiografía de tórax y un TCAR torácico y pruebas de función pulmonar como una espirometría y difusión pulmonar. La Calidad de Vida Relacionada con la Salud se ha evaluado a través de la administración del cuestionario genérico SF-36. Han participado un total de 305 pacientes que ingresaron por neumonía COVID-19, de los cuales 130 (42,6%) completaron el seguimiento a los 3 y 12 meses. La edad media del grupo de seguimiento fue de 55,9 ± 15,9 años. Los síntomas persistentes más prevalentes fueron disnea (37,3%) y astenia (36,9%) y se detectaron secuelas pulmonares en 27 participantes (8,8%). De ellos, 17 (5,5%) eran hombres y 10 (3,2%) mujeres. La alteración radiológica más frecuente fueron las opacidades en vidrio deslustrado (88,9%), con una extensión leve. Sólo se encontraron cambios fibróticos en el 2% de los casos. Al comparar el grupo de estudio con la población general, se detectó un deterioro significativo en todos los dominios del cuestionario SF-36 a los 3 y 12 meses tras la infección por COVID-19, excepto en la Salud Mental. Las mayores diferencias se dieron en el Rol Físico y en el Rol Emocional. Al estudiar las diferencias entre los pacientes con y sin secuelas pulmonares, a los 3 y 12 meses de evolución sólo se encontraron puntuaciones más bajas en los dominios de Vitalidad y Salud Mental en el grupo sin secuelas. Los días de hospitalización y el índice de Charlson actuaron como factores influyentes en la Calidad de Vida Relacionada con la Salud. En cuanto al género, las mujeres presentan puntuaciones más bajas en el cuestionario SF-36. La peor calidad de vida de las mujeres se mantuvo a los 12 meses, con diferencias estadísticamente significativas en la Función Física, la Salud General y la Vitalidad. La presente tesis doctoral aporta información relevante acerca de la infección por COVID-19 y su impacto en la Calidad de Vida Relacionada con la Salud. El objetivo de esta tesis doctoral consiste en analizar el estado de salud y la Calidad de Vida Relacionada con la Salud en pacientes que han superado una neumonía por COVID-19. Además, también tiene como objetivos específicos examinar su evolución, evaluar el impacto que las secuelas pulmonares post-COVID-19 tienen en la Calidad de Vida Relacionada con la Salud e identificar la influencia del género en la Calidad de Vida Relacionada con la Salud en pacientes que han desarrollado secuelas pulmonares tras la infección por SARS-CoV-2. Todo ello para, en última instancia, intentar aumentar los conocimientos sobre la enfermedad y con ello mejorar la calidad de la asistencia a los pacientes afectados por COVID-19. Con este propósito se ha diseñado un estudio observacional prospectivo de pacientes supervivientes a neumonía por SARS-CoV-2, entre febrero y mayo de 2020. Se ha realizado una evaluación a los 3 y 12 meses del inicio de la enfermedad de cada paciente. Los datos se han obtenido mediante la revisión de la historia clínica y la realización a los pacientes de una exploración física, pruebas de imagen como una radiografía de tórax y un TCAR torácico y pruebas de función pulmonar como una espirometría y difusión pulmonar. La Calidad de Vida Relacionada con la Salud se ha evaluado a través de la administración del cuestionario genérico SF-36. Han participado un total de 305 pacientes que ingresaron por neumonía COVID-19, de los cuales 130 (42,6%) completaron el seguimiento a los 3 y 12 meses. La edad media del grupo de seguimiento fue de 55,9 ± 15,9 años. Los síntomas persistentes más prevalentes fueron disnea (37,3%) y astenia (36,9%) y se detectaron secuelas pulmonares en 27 participantes (8,8%). De ellos, 17 (5,5%) eran hombres y 10 (3,2%) mujeres. La alteración radiológica más frecuente fueron las opacidades en vidrio deslustrado (88,9%), con una extensión leve. Sólo se encontraron cambios fibróticos en el 2% de los casos. Al comparar el grupo de estudio con la población general, se detectó un deterioro significativo en todos los dominios del cuestionario SF-36 a los 3 y 12 meses tras la infección por COVID-19, excepto en la Salud Mental. Las mayores diferencias se dieron en el Rol Físico y en el Rol Emocional. Al estudiar las diferencias entre los pacientes con y sin secuelas pulmonares, a los 3 y 12 meses de evolución sólo se encontraron puntuaciones más bajas en los dominios de Vitalidad y Salud Mental en el grupo sin secuelas. Los días de hospitalización y el índice de Charlson actuaron como factores influyentes en la Calidad de Vida Relacionada con la Salud. En cuanto al género, las mujeres presentan puntuaciones más bajas en el cuestionario SF-36. La peor calidad de vida de las mujeres se mantuvo a los 12 meses, con diferencias estadísticamente significativas en la Función Física, la Salud General y la Vitalidad. La presente tesis doctoral aporta información relevante acerca de la infección por COVID-19 y su impacto en la Calidad de Vida Relacionada con la Salud.

The world is grappling with an escalating risk of viral outbreaks of pandemic proportion, with zoonotic RNA viruses such as chikungunya virus (CHIKV) and SARS-CoV-2 posing significant threats to global health. Several environmental and evolutionary factors have fueled the emergence and spread of infection, creating a constant arms race against emerging pathogens. Current prevention and mitigation strategies are inadequate, necessitating tools to prevent and control viral infections; innovative strategies are needed in the pipeline to address significant challenges. CHIKV is a mosquito-borne virus that has caused millions of disease cases worldwide and is a reemerging threat with increasing potential to become endemic in the US. Currently, there are no licensed treatments available to protect against CHIK disease, making the development of a vaccine crucial. Live-attenuated vaccines (LAVs) have traditionally been a promising strategy due to their high immunogenicity and cost-effectiveness. However, concerns regarding adverse side effects and the potential for viral replication leading to pathogenic reversions or transmission into mosquitoes have limited their use. To that end, we have developed a new generation of safer vaccines by modifying the standard LAV platform through innovative attenuating strategies. Our dual-attenuated platform utilizes a previously developed chimera of CHIKV and the closely related Semliki Forest virus (SFV) as a vaccine backbone which expresses antiviral mouse cytokines IFN-γ or IL-21, as an additional mechanism to control infection. In several mouse models, both cytokine-expressing candidates showed reduced footpad swelling and minimal to no systemic replication or dissemination capacity compared to the parental vaccine post-vaccination. Importantly, these candidates conferred full protection from wildtype CHIK disease. Our IFNγ-expressing vaccine showed the most significant attenuation of viral replication. To understand the underlying mechanism, we identified three IFNγ-regulated antiviral genes (Gbp1/2 and Ido1) that were highly upregulated in 3T3 mouse fibroblasts post-infection with the IFN-γ-expressing candidate but not the parental backbone. To further investigate the role of these genes in restricting viral replication and enhance the clinical relevance of our vaccine platform, we redesigned our vaccine to express human IFNγ (hIFNγ) and performed viral growth kinetics in MRC5 human lung fibroblasts. Our vaccine showed reduced viral replication compared to controls and high expression of human GBP1/2/3 was observed post-infection. Overexpression of these genes demonstrated a direct impact on viral replication against wildtype CHIKV. These findings shed light on the mechanism of action of our vaccine and highlight the potential of targeting IFNγ-regulated antiviral genes for developing effective vaccines against CHIKV. Our results provided a foundation for investigating the broad-use application of IFN-γ against other alphaviruses for vaccine or therapeutic design. We evaluated the effects of increasing levels of exogenous hIFNγ on Mayaro virus (MAYV), Ross River virus (RRV), and Venezuelan Equine Encephalitis virus (VEEV). We observed a positive dose-dependent relationship between hIFNγ and decreasing viral titers for all three viruses. Interestingly, we also observed similar patterns of GBP upregulation with MAYV and RRV, both Old World alphaviruses, but not with VEEV, a New World alphavirus. This finding may indicate an alternative IFNγ-stimulated pathway responsible for controlling different alphaviruses. Overall, these studies establish a fundamental role of IFNγ in controlling viral infection and highlight its potential use in both vaccine and therapeutic intervention. While LAVs are a gold standard for developing immunity against a virus, the urgency of responding to an active and deadly pandemic has promoted the use of faster strategies such as mRNA vaccines. Once the viral sequence was known, these vaccines were comparatively quick to produce for SARS-CoV-2 and prevented millions of disease cases at the height of their introduction. However, the emergence of variants of concerns bypassing previous immunization efforts has demonstrated the need for complementary treatments such as antivirals to control disease. To that end, we evaluated several rhodium organometallic complexes as potential antivirals against SARS-CoV-2. We show that two pentamethylcyclopentadienyl (Cp*) rhodium piano stool complexes, Cp*Rh(ICy)Cl2 and Cp*Rh(dpvm)Cl are non-toxic in Vero E6 and Calu3 cells and reduce SARS-CoV-2 plaque formation up to 99%. These complexes have previously demonstrated high antimicrobial activity against multiple antibiotic-resistance bacteria and with our results, support their potential application as pharmaceuticals, warranting further investigation into their activity. / Doctor of Philosophy / The global response to the COVID-19 pandemic, and its far-reaching impact, revealed significant shortcomings in public health preparedness for emerging viruses. Despite efforts to develop vaccines and antivirals to prevent and treat disease, current mitigation strategies have proven insufficient to eradicate the pathogen. The emergence of viral outbreaks caused by viruses such as chikungunya (CHIKV) and SARS-CoV-2 underscores the ongoing threat posed by emerging infectious diseases. Improved countermeasures are urgently needed to address gaps in vaccine and antiviral development. CHIKV is a mosquito-borne virus that has caused millions of infections across hundreds of countries with the emergent potential to become endemic in the US. Currently, there are no vaccines available to the public; therefore, it is important to generate and administer an effective vaccine before further spread of the virus. To this end, we developed innovative live-attenuated vaccines (LAVs) against CHIKV using a weakened chimeric backbone of CHIKV and its close relative, Semliki Forest virus (SFV), along with vaccine-driven expression of antiviral cytokines to control viral replication. Vaccination of highly susceptible mice with these cytokine-expressing vaccines produced significantly decreased side-effects compared to the parental virus not expressing the cytokines. Additionally, these viruses had significantly restricted viral replication capabilities while robustly protecting mice from a semi-lethal CHIKV infection. Our interferon-gamma (IFNγ) expressing vaccine had the greatest impact on viral replication, and we investigated the mechanism leading to this attenuation. To assess the clinical relevance of our vaccine platform, we redesigned the virus to express human IFNγ and identified a specific pattern of IFNγ-stimulated genes that are potentially responsible for limiting CHIKV replication. Furthermore, we demonstrated the broad therapeutic use of IFNγ against other medically relevant alphaviruses. Overall, these studies establish an improved mechanism to create safer vaccines without compromising efficacy and highlight the therapeutic potential of IFNγ against alphaviruses. Lastly, in a collaborative effort to respond to the COVID-19 pandemic, we also explored and characterized the use of a new class of antiviral drugs. With the advent of increasing drug resistance, it is essential to develop novel and resilient therapeutics. We demonstrated the first antiviral potential of rhodium organometallics, which was previously shown to be effective against multiple antibiotic-resistant bacteria. Two complexes demonstrated high virucidal activity against SARS-CoV-2 and low toxicity in mammalian cell lines. Moreover, these complexes can be further derivatized to improve efficacy, making them a promising new antiviral strategy.

<p dir="ltr">The recent global pandemic, COVID-19, has revealed to all the importance of understanding the complex relationship between viruses and hosts. Before COVID-19, I started my study of viral protein-host lipid interactions in the hemorrhagic fevers Ebola and Marburg viruses. These viruses contain a matrix protein that interacts with the plasma membrane to facilitate the formation of both authentic viruses and virus-like particles. My goal was to understand the limitations of their specific host lipid interactions. However, when the COVID-19 pandemic began, so to be our swift response in the development of a biosafety level 2 compatible model. This model can be used for studying severe acute respiratory distress syndrome 2 (SARS-CoV-2) assembly, egress, and entry. This model enabled exponentially greater access to more facilities to study the intricacies of SARS-CoV-2 assembly. With more access to studying the virus in a safe model, our goal is to push the understanding of viral assembly faster. I then began to take apart the individual pieces of the model and started to look at understanding the roles that they play independently. The membrane protein is the most abundant structural protein and I studied the specific lipid interactions of the soluble fraction of the protein. Physicians observed nucleocapsid protein mutations in the clinic with the increasing number of SARS-CoV-2 variants that are on the rise. The microscopy data collected can give us more insight into perhaps how the nucleocapsid protein induces the formation of filopodia structures at the plasma membrane. The envelope protein proved to be a challenge, but I determined a specific envelope and ceramide interaction in cells. The envelope protein was also causing the formation of microvesicles for an undefined function. I was able to determine the subcellular localization of the protein to the mitochondria. The localization to the mitochondria appears to induce depolarization of the mitochondria membrane action potential and induces the increase in mitochondria dysfunction signal, cytochrome c. Although the mitochondria were dysfunctional, there was no increase in apoptosis signal in the presence of the protein alone.</p>

Yes / Introduction. Coronavirus disease 2019 (COVID-19) was first detected in China in December, 2019, and declared as a pandemic by the World Health Organization (WHO) on March 11, 2020. The current management of COVID-19 is based generally on supportive therapy and treatment to prevent respiratory failure. The effective option of antiviral therapy and vaccination are currently under evaluation and development. Areas covered. A literature search was performed using PubMed between December 1, 2019–June 23, 2020. This review highlights the current state of knowledge on the viral replication and pathogenicity, diagnostic and therapeutic strategies, and management of COVID-19. This review will be of interest to scientists and clinicians and make a significant contribution toward development of vaccines and targeted therapies to contain the pandemic. Expert Opinion. The exit strategy for a path back to normal life is required, which should involve a multi-prong effort toward development of new treatment and a successful vaccine to protect public health worldwide and prevent future COVID-19 outbreaks. Therefore, the bench to bedside translational research as well as reverse translational works focusing bedside to bench is very important and would provide the foundation for the development of targeted drugs and vaccines for COVID-19 infections. / Research carried out at TN laboratories are funded by the GrowMedtech, The Royal Society and University of Bradford. KH is supported by a project grant by the GrowMedtech awarded to TN. CW is funded by a Ph.D studentship.

Depuis l'émergence de la pandémie de SARS-CoV-2 en décembre 2019, plus de 675 millions de cas confirmés ont été signalés dans le monde, dont 4,6 millions de cas au Canada uniquement. Bien que la plupart des individus récupèrent sans séquelles, 10 à 20 % des survivants signalent des symptômes persistants au-delà de quatre semaines après une infection par le SARS-CoV-2, tels que la fatigue, les altérations cognitives, la toux, l'anxiété, la dépression, la douleur thoracique et autres, connus sous le nom de COVID longue ou de condition post-SARS-CoV-2 (PCC). Par conséquent, la physiopathologie, le diagnostic et la prise en charge de la PCC sont devenus un axe de recherche majeur. Pour contribuer à la compréhension de la PCC, nous avons mené le projet IPCO (Institut de Recherches cliniques de Montréal (IRCM) Post-COVID-19 Research Clinic), en posant comme hypothèses 1 que les personnes infectés par le SARS-CoV-2 au Québec présenteraient des signes et symptômes fréquents et variés post-phase aiguë, affectant différents systèmes d'organes, et 2 Les niveaux élevés de D-dimères dans PCC ne sont pas pertinents pour les événements thromboemboliques 3 que Chez les individus atteints de la PCC, la vaccination contre la COVID-19 réduirait les symptômes de la PCC en diminuant l'inflammation. Pour évaluer ces hypothèses, nous avons recruté des participants âgés de plus de 18 ans, un à 18 mois après l'infection aiguë, présentant au moins un symptôme persistant, et programmé des visites de base et de suivi à 3-6 mois, 1 an et 2 ans post-infection aiguë. Chaque visite comprenait des évaluations cliniques, des prélèvements, des évaluations en laboratoire, des questionnaires sur l'alimentation et le bien-être, ainsi que des évaluations de la physiologie pulmonaire et cardiaque. Sur la base d'une étude allemande qui a catégorisé les symptômes du PCC et les individuals en trois groupes de sévérité, nous avons classé nos participants en trois niveaux de sévérité : non/légère (score du PCC <10,75), modérée (10,75 < score du PCC < 26,25) et sévère (score du PCC > 26,25). Cette thèse présente les résultats de trois sous-études IPCO. Dans l'étude descriptive, nous avons observé que la fatigue, les problèmes de mémoire et les maux de tête étaient les symptômes de PCC les plus courants, la majorité de nos participants étant des femmes et ayant été traités en ambulatoire pendant la phase aiguë. Dans l'étude transversale, nous avons constaté des différences significatives dans les mesures de santé et de bien-être à tous les moments, mais aucune différence significative dans les résultats des tests physiologiques entre les groupes PCC non/léger, modéré et sévère. Dans l'étude longitudinale, les marqueurs de l'inflammation se sont améliorés au fil du temps, mais le taux métabolique basal et la masse grasse ont augmenté. Dans la deuxième étude, nous avons observé une forte prévalence de participants ayant des niveaux de D-dimères, qui n'étaient pas associés à des événements thromboemboliques, et aucune corrélation entre le niveau de D-dimères et les niveaux de cytokines et de chimiokines. Dans la troisième étude, nous avons observé que les participants vaccinés présentaient significativement moins de symptômes de PCC. Notre étude fournit une meilleure compréhension de la physiopathologie du PCC et de l'effet de la vaccination sur le profil clinique et inflammatoire du PCC, ce qui pourrait aider à la conception d'outils de gestion clinique et de recherche futurs. / Since the emergence of the SARS-CoV-2 pandemic in December 2019, over 675 million confirmed cases have been reported globally, with 4.6 million cases in Canada alone. Although most individuals recover without residual disease, 10-20% of survivors report symptoms persisting beyond four weeks after SARS-CoV-2 infection, such as fatigue, cognitive impairments, cough, anxiety, depression, chest pain, and others known as long-COVID or post SARS-CoV-2 condition (PCC). Consequently, the pathophysiology, diagnosis, and management of PCC have become a significant focus of research. To contribute to the understanding of PCC, we conducted the IPCO (Institut de Recherches cliniques de Montréal (IRCM) Post-COVID-19 Research Clinic) project, hypothesizing that 1 SARS-CoV-2 infected individuals in Quebec would present frequent and varied signs and symptoms post-acute phase, affecting different organ systems, and that 2 high D-dimer level in PCC is irrelevant to thromboembolic events , and 3 in individuals with PCC, COVID-19 vaccination would decrease PCC symptoms by reducing inflammation. To evaluate these hypotheses, we enrolled participants aged >18 years, one to 18 months post-acute infection, with at least one persistent symptom, and scheduled baseline and follow-up visits at 3-6 months, 1 year, and 2 years post-acute infection. Each visit involved clinical evaluations, sampling, laboratory evaluations, diet and well-being questionnaires, and pulmonary and cardiac physiology evaluations. Based on a German study that categorized PCC symptoms and individuals into three severity groups, we classified our participants into three severity levels: non/mild (PCC score < 10.75), moderate (10.75 < PCC score < 26.25), and severe (PCC score > 26.25). This thesis reports the results of three IPCO studies. In the descriptive study, we observed that fatigue, memory problems, and headaches were the most common PCC symptoms, with the majority of our participants being female and managed as outpatients during the acute phase. In the cross-sectional study, we noted significant differences in health and well-being measurements at all time points, but no significant difference in physiological tests' results between different severity groups. In the longitudinal study, markers of inflammation improved over time, but the basal metabolic rate and body fat increased. In the second study, we observed a high prevalence of participants having D-dimer levels in blood, which were not associated with thromboembolic events, and no correlation between D-dimer levels and blood cytokine/ chemokine levels. In the third study, we observed that vaccinated participants had significantly fewer PCC symptoms, fewer organ systems affected, higher well-being scores, and lower blood cytokine/chemokine levels than the non-vaccinated group. We also observed correlations between certain cytokines/chemokines, as well as between clinical parameters and certain cytokines/chemokines. Our study provides a better understanding of the pathophysiology of PCC and effect of vaccination on the clinical and inflammatory profile of PCC, which could assist future research and clinical management tool design.

The rapidly spreading pandemic of SARS-CoV-2 (COVID-19) infection with high morbidity and mortality has overwhelmed the global healthcare services. With mysterious origins and the capacity of affecting multiple types of tissues, SARS-CoV-2 has baffled many scientists - which has posed great challenges in the development of pharmaceutical treatments and preventions (i.e., vaccination). The COVID-19 pandemic has also led to a slew of non-pharmaceutical interventions (NPIs) to slow down the spread of the virus. The sudden imposition of these NPIs including social distancing, lock-down, school closures, isolation, and quarantine of suspected cases or contacts, has greatly affected the mental health of children and adolescents. Concerns about the impact of these NPIs on mental health, especially for vulnerable populations such as children and adolescents, have emerged. This study discusses several different aspects of the impact of the COVID-19 pandemic on the mental health of children and adolescents.Accumulating evidence has shown that the vast majority of children and adolescents exposed to the SARS-CoV-2 virus are asymptomatic, although few cases turned unfortunately severely ill. The genomics, microbiology, and biochemistry of this novel coronavirus reveal several peculiarities, making it a tough entity. The profound impact of social distancing along with the closure of schools, parks, and other recreational activities on the delicate minds of children and adolescents makes them irritable, angry, and rebellious. This assumes a major challenge in children with mental health issues or in those with special needs. Lock-down, quarantine and isolation further complicate the mental health issues and are discussed along with remedial measures. The impact of an already overwhelmed medical care system on the mental healthcare quality can be profound and needs a specially chartered approach by the psychiatrists supplementing the COVID-19 control activities. Children/adolescents with neuropsychiatric issues need special care, as they have abnormal impulsive behaviour and actions such as running away, unhygienic acts, spitting etc. All these mental health issues in children and adolescents, who form a sizable population of the society and are the future of the planet, forms the subject matter of this work. Thus, all programmes of COVID-19 control must simultaneously address these important mental health issues of children and adolescents to prevent this ‘parallel pandemic’ of psychiatric disorders. The latter may persist much longer and prove equally challenging and costly.

Objetivo: Desarrollar una metodología para evaluar el nivel de protección respiratoria de respiradores, mascarillas quirúrgicas y mascarillas comunitarias que usa la población peruana, usando partículas de un tamaño similar a las que contienen al virus activo del SARS-CoV-2. Materiales y métodos: Se ha determinado una relación lineal directa entre el logaritmo de la concentración de partículas suspendidas en aire y el tiempo transcurrido; por lo cual es posible comparar la cantidad de partículas internas y externas a la mascarilla o respirador en un mismo periodo y conocer el porcentaje de protección respiratoria de cada muestra evaluada. Resultados: Se ha logrado implementar una metodología para evaluar el nivel de protección respiratoria ante aerosoles menores a 5,0 μm. Asimismo, el empleo de accesorios como ligas o ajustadores detrás de cabeza y nuca, y el uso de clips nasales robustos, incrementan significativamente el nivel de protección respiratoria ante partículas con alta probabilidad de contener al SARS-CoV-2. Conclusiones: Se observa una concordancia entre los valores de protección respiratoria obtenidos y los esperados, considerando el nivel de filtración del material empleado de cada mascarilla quirúrgica o respirador, y su nivel de ajuste. Se observó un incremento significativo en los niveles de protección respiratoria. / Objective: To develop a methodology for evaluating the level of respiratory protection provided by res- pirators, surgical masks and community face masks used by the Peruvian population; protection was evaluated against particles of a size similar to those containing active SARS-CoV-2 virus. Materials and methods: A direct linear relationship has been determined between the logarithm of the concentration of airborne particles and the elapsed time; thus, it is possible to compare the quantity of particles inside and outside of the mask or respirator in the same time period, as well as to obtain the percentage of re- spiratory protection for each evaluated sample. Results: A methodology was established to evaluate the level of respiratory protection against aerosols smaller than 5.0 μm. Also, the use of accessories such as garters or adjusters behind the head and neck, and the use of strong nasal clips, significantly increased the level of respiratory protection against particles with a high probability of containing SARS-CoV-2. Conclusions: We found concordance between the obtained respiratory protection values and those ex- pected, considering the filtration level of the material used for each surgical mask or resp s well as the tightness. A significant increase in the levels of respiratory protection was observed.