Yes / Coronavirus is the most dangerous virus in the world wide and it can easy spread between people, animals and plants because it is existing on one strand of RNA (Ribonucleic Acid) and it can duplicate faster than any virus. The source of coronavirus is still unknown, but some sources said that it came from seafood market and other sources said that it came from bat and snakes. It starts in Wuhan; China and every day the fatality increases. The symptoms are like a SARS-CoV (acute respiratory syndrome coronavirus)) and MERS-CoV (Middle East Respiratory Syndrome Coronavirus). By using nucleotide sequence of coronavirus from NCBI (National Center for Biotechnology Information) and some programs that ran on Matlab, the results show that there are some differences and similarities between coronavirus and other viruses such as Ebola, Flu-b, Hepatitis B, HIV and Zika especially for DEBs (distinct excluded blocks) program that shows at 5bp (base pair) there is a common with slightly difference between coronavirus “cgggg” and Ebola virus “cgtgg”. The aim from this study is to find a way to help doctors and scientists to stop spreading the coronavirus or to destroy it.

The COVID-19 pandemic, caused by SARS-CoV-2, has emerged as one of most significant health emergencies in recent history. SARS-CoV-2 has been characterized by the emergence of highly mutated variants that exhibit high transmissibility, virulence, and the capability of immune escape. The constantly evolving nature of the COVID-19 pandemic has underscored the necessity for a thorough comprehension of viral transmission dynamics, the effectiveness of novel monitoring techniques, and the determinants of health inequalities. This study explored several aspects of the pandemic, specifically emphasizing the emergence and dissemination of the Delta variant in Florida, the significance of environmental surveillance, and the factors associated with COVID-19 outcomes. Phylogenetic analysis using SARS-CoV-2 genome revealed that multiple independent introductions of the Delta variant fueled its spread within Florida. Further, we hypothesized that high-touch surface monitoring can be an alternative noninvasive approach to determine infection trend and detect variants. The study found high contamination rate on high-touch surfaces and the viral gene copy was positively correlated to the clinical cases in the university. Moreover, genome sequencing of environmental surface samples detected circulating and emerging variants. Additionally, spatial autocorrelation and regression analysis was conducted to investigate the relationship between county-level demographic, socioeconomic, and health-related factors and variation in COVID-19 cases, mortality, and case fatality rates. This study identified significant variations in COVID-19 outcomes across Florida counties, with factors such as age, obesity, rurality and importantly, vaccination rates playing key roles in explaining these disparities. Overall, this study emphasizes the importance of robust genomic surveillance for monitoring the emergence and spread of viral variants, the potential of environmental surface monitoring as a complementary public health tool, and the urgent need to address the underlying drivers of health disparities. These findings contribute to a more nuanced understanding of pandemic dynamics and inform data-driven strategies to mitigate the impact of future public health emergencies.

A rural-urban divide in health status and healthcare infrastructure has been well-documented in the U.S., where populations residing in census regions classified as rural often exhibit more negative health outcomes, adverse health behaviors, and have reduced access to affordable and proximal health services, compared to their urban and peri-urban counterparts. However, it is important to note that such disparities vary based on specific rural regions and individual circumstances. Rural areas may face elevated risk factors for infectious diseases such as increased proximity to wildlife and livestock and disproportionately high reliance on private, non-federally regulated, primary drinking water sources. Chronic conditions prevalent in rural communities such as diabetes and hypertension are frequently linked with longer duration and higher severity of symptoms than in urban areas; this association suggests that the risk of exposure to infectious diseases and the likelihood of progression to serious illness and hospitalization may be elevated, although this is not universally the case across all rural settings. Alongside documented urban-rural health disparities, there also exist disparities in the nature and quality of data on health-related behaviors, outcomes, and service provision in rural areas compared to urban and peri-urban regions. In this dissertation, two key environmental matrices –drinking water and wastewater– were highlighted as vectors of information to better estimate levels of contaminant exposures and health outcomes in rural communities. First, baseline data on drinking water contaminant levels and associated health outcome data were highlighted as crucial for refining holistic exposure estimates as well as understanding drinking water related health burdens in rural communities where a larger proportion of households use private drinking water sources, such as well water, that are not federally regulated. Second, systematic sampling and testing of pathogen biomarkers in wastewater to non-invasively measure population-level health status, also known as wastewater based surveillance (WBS) and, depending on the context, wastewater based epidemiology (WBE) is not constrained by disadvantages of clinical testing, e.g., limited health-care access, long travel times to testing facilities, delay between symptom-onset and testing. Thus, expanded implementation of WBS in rural communities is proposed here as a strategy to address data disparities in clinical testing for infectious diseases. Collectively, this dissertation advances knowledge on estimated drinking water contaminant levels, exposures, and associated public health outcomes and corresponding research gaps in rural Appalachian U.S., and elucidates pathways toward best practices and considerations for public-health focused wastewater testing adoption in rural communities. For the latter, the question of whether WBS challenges unique to rural wastewater systems hinder application of WBS in small, rural communities was explored, as well as methods to advance best-practices for rural WBS. To summarize existing publicly available peer-reviewed literature on drinking water contaminants in rural Appalachian U.S., in Chapter 2, a systematic review and meta-analysis of microbial and chemical drinking water contaminants was performed. Key contaminants were identified as being elevated beyond regulatory, health-based, maximum contaminant levels in our meta-analyses from rural drinking water sources in Appalachia, including E coli, lead, arsenic, uranium. Overall, we found data on drinking water source quality under baseline conditions (i.e., rather than post anomalous contamination events such as chemical spills) in rural Appalachian U.S. was sparse relative to widespread media coverage on the issue. Epidemiologic-based research studies that collected both drinking water exposure data and paired health outcome data were also limited. As a result, although some instances of anomalously high levels of drinking water contaminants were identified in rural Appalachia from the published literature, we could not obtain a clear picture of baseline exposures to drinking water contaminants in most rural Appalachian communities, highlight need to address these knowledge gaps. In Chapter 3, to evaluate whether wastewater could serve as a reliable metric for estimating community circulation of viruses and antimicrobial resistance (AMR) markers, even when sourced from aging and low-resource sewer collection networks, a 12-month wastewater monitoring study was conducted in a small, rural sewer conveyance system with pronounced infrastructural challenges. Specifically, the field site under study was compromised with heavy inflow and infiltration (IandI). Detection rates and concentrations of viral, AMR, and human fecal markers were grouped by levels of IandI impact across the sewershed, and location-, date-, and sample- specific variables were assessed for their relative influence on viral, AMR, and human fecal marker signal using generalized linear models (GLMs). We found that while IandI likely adversely impacted the magnitude of wastewater biomarker signal to some extent throughout the sewershed, especially up-sewer at sites with more pronounced IandI, substantial diminishment of wastewater signal at WWTP influent was not observed in response to precipitation events. Thus, our data indicated that WWTP influent sampling alone can still be used to assess and track community circulation of pathogens in heavily IandI impacted systems, particularly for ubiquitously circulating viruses less prone to dilution induced decay. Delineations were also made for what circumstances up-sewer sampling may be necessary to better inform population shedding of pathogens, especially where IandI is prevalent. Various normalization strategies have been proposed to account for sources of variability for deriving population-level pathogen shedding from wastewater, including those introduced by IandI-driven dilution. Thus, in Chapter 4, we evaluated the temporal and spatial variability of viral and AMR marker signal in wastewater at different levels of IandI, both unnormalized and with the adoption of several normalization strategies. We found that normalization using physicochemical-based wastewater strength metrics (chemical oxygen demand, total suspended solids, phosphate, and ammonia) resulted in higher temporal and site-specific variability of SARS-CoV-2 and human fecal biomarker signal compared to unnormalized data, especially for viral and AMR marker signal measured in wastewater from sites with pronounced IandI. Viral wastewater signal normalized to physicochemical wastewater strength metrics and flow data also closely mirrored precipitation trends, suggesting such normalization approaches may more closely scale wastewater trends towards precipitation patterns rather than per capita signal in an IandI compromised system. We also found that in most cases, normalization did not significantly alter the relationship between wastewater trends and clinical infection trends. These findings suggest a degree of caution is warranted for some normalization approaches, especially where precipitation driven IandI is heightened. However, data and findings largely supported the utility of using human fecal markers such as crAssphage for normalizing wastewater signal to address site-specific differences in dilution levels, since viral signal scaled to this metric did not result in strong correlations between precipitation and wastewater trends, higher spatial and temporal variation was not observed, and strong correlations were observed between viral signal and viral infection trends. Finally, in chapter 5, we assessed the relationship between monthly Norovirus GII, Rotavirus, and SARS-CoV-2 wastewater trends with seasonal infection trends for each of the viruses to ascertain whether WBE could be used in a rural sewershed of this size with substantial IandI impacts to track and potentially predict population level infection trends. Though up-sewer, or near-source sampling, at sites with permanent IandI impacts did not exhibit a clear relationship with seasonal infection trends for Rotavirus, SARS-CoV-2, and Norovirus GII, WWTP influent signal and consensus signals aggregated from multiple up-sewer sites largely mirrored expected seasonal trends. Findings also suggested that for more ubiquitous viral targets, such as SARS-CoV-2, viral trends measured at WWTP influent in a small IandI impacted system may still provide a sufficiently useful measure of infection trends to inform the use of WBE (assuming appropriate normalization to sewershed population). These findings elucidate the potential utility and relative robustness of wastewater testing to ascertain community-level circulation of pathogens in small, rural sewersheds even those compromised by extensive IandI inputs. Overall, this dissertation examined drinking water and wastewater as critical metrics for assessing contaminant exposures and infectious disease trends in rural communities, particularly in the context of small, rural communities which tend to have more limited health infrastructure and lower-resource wastewater systems. Overall, findings underscore the need for baseline data on drinking water quality by identifying gaps in current knowledge and calling for further research to better understand drinking water contaminant exposure levels in rural areas. Wastewater as a non-invasive, population-level health metric was evaluated in the context of a small, rural sewer system overall, and by varying observed levels of IandI, as well as associated tradeoffs for normalization adoption. By evaluating these environmental surveillance metrics using both desk-based and field-based research study designs, findings from this dissertation offer valuable insights and practical recommendations for improving baseline drinking water quality monitoring and wastewater pathogen testing, all with the overarching goal of supporting more targeted public health interventions in rural settings. / Doctor of Philosophy / In the United States, there is a significant health and healthcare gap between rural and urban areas. Rural communities often face worse health outcomes, poorer health behaviors, and have less access to affordable and nearby healthcare services compared to their urban and peri-urban counterparts. Additionally, rural areas are exposed to higher risks for infectious diseases due to closer proximity to wildlife and livestock and proportionately lower access to regulated drinking water sources. Chronic conditions like diabetes and hypertension, which are more common in rural populations, can exacerbate the severity and duration of symptoms for infectious diseases, potentially leading to more serious illness and hospitalizations. Despite these heightened risks, data on health behaviors, outcomes, and healthcare services in rural areas is often lacking and less comprehensive compared to urban regions. This dissertation investigates two promising avenues of improving monitoring to provide information needed to better understand and address contaminant exposures and health trends in rural communities: drinking water and wastewater. Firstly, this dissertation underscores the importance of establishing baseline data on drinking water quality. This is essential for accurately estimating exposure levels and understanding the health impacts associated with elevated levels of drinking water contaminants, particularly in rural areas where a higher share of primary drinking water sources is unregulated by the federal government compared to urban areas. This study reveals significant gaps in current knowledge and highlights the need for more research to provide a clearer picture of drinking water quality in these communities. Secondly, this dissertation explores the use of wastewater as a non-invasive tool for assessing community health. This method, known as wastewater-based surveillance (WBS) or wastewater-based epidemiology (WBE), offers a way to measure population-level health trends without relying on clinical testing, which can be limited by factors such as access to healthcare and delays in testing. The dissertation evaluates how effective wastewater monitoring can be in small, rural sewer systems, even when these systems face challenges like aging infrastructure and significant inflow and infiltration (IandI) from groundwater and surface water. It examines how different normalization strategies for wastewater data can influence the reliability of this method and how wastewater testing can be adapted to account for varying levels of IandI. Overall, the dissertation provides valuable insights into the effectiveness of using drinking water and wastewater as environmental metrics for informing public health intervention strategies in rural settings. It offers justifications for improving drinking water quality monitoring and wastewater testing practices, aiming to support more targeted and effective public health interventions in rural communities. By addressing the challenges and limitations associated with these environmental monitoring strategies this research contributes to a better understanding of how to reduce health data disparities in rural areas.

La pandémie de la COVID-19 a été causée par le virus SARS-CoV-2. Il est maintenant compris que ce virus peut être transmis par des aérosols émis par une personne infectée vers une personne saine. En raison de ce type de transmission, les environnements de soins de santé tels que les hôpitaux et les centres de soins de longue durée doivent protéger leurs patients, mais aussi leurs travailleurs. Pour ce faire, les patients sont hébergés dans des chambres à pression négative qui empêchent l'air contaminé de sortir de la pièce sans être filtré. L'objectif de cette étude est d'identifier l'exposition des travailleurs au virus SARS-CoV-2 à l'intérieur et à l'extérieur de la chambre du patient. Le premier objectif de cette étude était de caractériser l'émission virale des patients positifs à la COVID-19. Des échantillons d'air ont été collectés sur une période de 24 heures à l'intérieur des chambres des patients positifs. Les données cliniques des patients échantillonnés ont été recueillies par le personnel de santé pour tenter de prédire les variations des taux d'émission des patients. Le deuxième objectif de l'étude était d'évaluer la contamination de l'air à l'extérieur des chambres des patients. Des surfaces ont été utilisées comme indicateur indirect de la contamination de l'air. Ces surfaces ont été échantillonnées avant et pendant 6 semaines consécutives après le nettoyage pour analyser l'évolution de la contamination virale dans le temps. L'ARN de SARS-CoV-2 était présent dans 63,7 % des échantillons d'air collectés, et le taux moyen d'émission était mesuré à 1,11E+06 génomes/personne/heure. Aucune donnée clinique collectée n'avait de relation significative avec le taux d'émission des patients. L'échantillonnage de surface montre une quantité détectable d'ARN viral sur 4 des 15 surfaces, et aucune contamination jusqu'à 6 semaines après le nettoyage. La détection de l'ARN viral dans l'air des chambres des patients, mais l'absence de facteurs expliquant les variations des taux d'émission observés, confirme la nécessité de comprendre l'émission du virus par les patients pour mieux protéger les travailleurs de la santé. L'échantillonnage de surface effectué à l'extérieur des chambres indique que l'isolement des patients positifs au virus de la COVID-19 dans des chambres à pression négative a empêché l'air contaminé de quitter la pièce, protégeant ainsi les travailleurs à proximité. / The COVID-19 pandemic is a global health crisis caused by the SARS-CoV-2 virus. It is now understood that the virus can be transmitted by aerosols emitted from an infected person to a healthy one. Because of this type of transmission, healthcare environments like hospitals and long-term care centers need to protect their patients but also their workers. To do this, patients are housed in negative pressure rooms that prevent contaminated air from exiting the room without being filtered. The goal of this study was to characterize the SARS-CoV-2 virus exposure to workers inside and outside the patient's room. The first objective of this study was to characterize viral emission from COVID-19 positive patients. Air samples were collected for a period of 24 hours inside positive patient's rooms. Clinical data of patients in the sampled rooms were collected by healthcare staff to try to predict variations in patient's emission rates. The second objective of the study was to evaluate the air contamination in zones outside of patient's rooms. Surfaces were used as an indirect air contamination indicator. These surfaces were swabbed before and for 6 consecutive weeks after cleaning to analyze the evolution of the contamination through time. SARS-CoV-2 RNA was present in 63.7% of the air samples collected and the mean emission rate was measured at 1.11E+06 genomes/person/hour. No collected clinical data collected was associated to patient emission rate. Surface swabbing showed detectable quantity of viral RNA on 4 of the 15 surfaces and no contamination up to 6 weeks after cleaning. The detection of viral RNA in the air of patients' rooms but the lack of factors explaining the variations in emission rates observed confirms the need to better understand virus emission by patients to better protect healthcare workers. Surface sampling outside the rooms indicated that the isolation of patients positive for SARS-CoV-2 in negative pressure rooms prevented contaminated air from leaving the room, thereby protecting healthcare workers.

L’entrée des polluants gazeux du sol (Radon, COV,…) dans les environnements intérieurs peut occasionner des risques sanitaires significatifs. Or les modèles d’évaluation de risques sanitaires liés à ces polluants gazeux du sol contiennent beaucoup d’incertitudes qui peuvent conduire à une mauvaise appréciation des risques. Dans un premier temps, cette thèse contribue à l’amélioration des modèles d’évaluation des risques. Dans un second temps, elle propose le développement d’un modèle de dimensionnement des Systèmes de Dépressurisation du Sol (SDS) passifs utilisés pour protéger les bâtiments des pollutions gazeuses venant du sol. L’amélioration des modèles a porté sur la prise en compte des principaux phénomènes de convection et diffusion à l’interface entre le sol et le bâtiment, en tenant compte des différentes typologies de soubassement. La première contribution porte sur le développement de modèles analytiques fournissant les débits d’air dus à la convection à travers le sol pour différents types de soubassement : dallage indépendant, dalle portée, vide sanitaire et cave. Les bâtiments avec des murs enterrés et les soubassements avec un lit de gravier sous le plancher bas sont également traités. Une méthodologie permettant la prise en compte de la fissuration et des points singuliers du plancher bas est aussi proposée. La deuxième contribution porte sur la prise en compte du transfert couplé des polluants des sols par convection et diffusion auprès des fondations. Une étude numérique a permis une meilleure compréhension du comportement des polluants à l’interface sol/bâtiment. Sur la base de cette compréhension, des lois semi-empiriques d’estimation des flux d’entrée de polluant dans les bâtiments sont proposées. Les différents modèles développés ont été validés numériquement avec un modèle CFD et expérimentalement avec des données issues de la littérature. La confrontation de ces modèles avec ceux existants a montré les améliorations apportées. L’impact de la typologie du soubassement sur le transfert de polluants gazeux des sols a été constaté. Une première application des modèles est illustrée par leur intégration dans un code de simulation thermo-aéraulique multizone afin de pouvoir étudier l’impact de ces polluants sur la qualité de l’air intérieur. Ce travail se termine par le développement d’un modèle de dimensionnement des Systèmes de Dépression du Sol (SDS) passifs. Ce modèle aéraulique de dimensionnement des SDS a été validé par des mesures effectuées au CSTB dans une maison expérimentale. Les premières applications du modèle de dimensionnement portent notamment sur l’impact de la météorologie (vent et tirage thermique) sur le fonctionnement du SDS passif et sur l’impact des stratégies de ventilation du bâtiment sur le fonctionnement du SDS passif. On voit ainsi l’intérêt de l’utilisation d’un tel modèle pour tester l’aptitude de ce système de protection des bâtiments dans des situations environnementales données. / Transfer of soil gas pollutants (Radon, VOC) into buildings can cause significant health risks. However, analytical models used today to estimate health risks associated with these pollutants contain many uncertainties which can lead to poor risk assessment. Initially, the main objective of this thesis is to contribute to the improvement of these models for risk assessment. Secondly, we propose the development of air flow model for passive Sub slab Depressurization Systems (SDS) design used to protect buildings. The improvement of models focused on the inclusion of the main phenomena of convection and diffusion at building/soil interface, taking into account different types of building substructures. The first improvement concerns the assessment of convection phenomenon through the development of analytical models to quantify air flow rates entering through many kinds of building substructures: floating slab, bearing slab, crawl space and basement. Buildings with buried walls and substructures with a sub slab gravel layer are also treated. A methodology taking into account the presence of cracks, holes and singular leakages of the slab is also proposed. The second improvement of the models is the inclusion of coupled transfer of convection and diffusion near foundations. A numerical study allowed a better understanding of the behavior of pollutants at soil / building interface. Based on this understanding, semi-empirical laws for estimating soil gas pollutants entry rate into buildings are proposed. The various models developed have been validated numerically using a CFD model and experimentally with data from the literature when available. The impact of building substructure on pollutant transfer has been highlighted. A first application of the model is illustrated by their integration into a multizone simulation code to study the impact of these transfers on indoor air quality. Finally, the work ends with the development of a model for designing passive sub slab depressurization systems. The design model developed is validated with in situ experimental data. Preliminary applications using this model focused at first on the impact of meteorological conditions (stack effect, wind) on the sub slab system running. At second, the impact of ventilation strategies on sub slab depressurization performance is studied. Thus, we see the potential interest of this model to test the effective running of passive sub slab depressurization systems in given configuration.

L'évaluation de l'inertie des matières plastiques au contact de denrées alimentaires est régie par le règlement européen N°10/2011. Au Liban, l'absence de législations relatives à l'usage des matières en plastiques a conduit à des emballages non contrôlés au niveau de la production et du stockage, ce qui peut induire un risque sanitaire pour le consommateur. L'objectif de ce travail a été d'apprécier les phénomènes de migration des contaminants du PET vers l'eau. Pour cela, l'analyse de certains migrants potentiels a été initiée tels que des COV et des SV afin de vérifier la conformité de leur teneur par rapport aux LMA dans les règlementations internationales. Le dosage des aldéhydes dans l'eau a été effectué par dérivation avec la 2,4-DNPH, suivie d'une étape de préconcentration sur une cartouche en C18, puis séparation et quantification par HPLC-UV. L'analyse des composés SV a été réalisée par SPME-GC-FID sur une fibre en PDMS/DVB. L'analyse des BTEX et du styrène a été réalisée par HS-Trap-GC-FID. Ces méthodes ont été validées conformément à la norme NF T 90-210 avec des LQ inférieures aux LMA. L'analyse des COV dans l'eau embouteillée et dans le PET a été réalisée par HSTrap- GC-MS. La présence de FA, d'AA, de DEP et des BTEX dans l'eau embouteillée en PET a été confirmée. Il a été mis en évidence que la température et l'exposition solaire influencent la migration des aldéhydes. Les concentrations d'AA trouvées après incubation à 40ºC ne sont pas négligeables et peuvent modifier les propriétés organoleptiques de l'eau. L'analyse du PET montre la présence des hydrocarbures, des aldéhydes, des alcools, et des cétones / The inertness’ value of plastics that are on contact with foodstuffs is governed by the European rule N°10/2011. In Lebanon, the lack of the Rules and Regulations of plastics’ usage led for a non-controlled packing in production as in storage, which will cause a sanitary risk to the consumer and to the population. The purpose of this research was to appreciate the migration’s phenomena of contaminants from the PET to the water. For this, there was an analysis of potential migrants such as VOC and SV to verify their tenor’s conformity relative to the MCL in international regulations. The aldehydes’ dosage in the water was performed by the derivation with the 2,4-DNPH, followed by a concentration on a C18 cartridge, then separation and quantification was done by HPLC-UV. The SV compounds’ analysis was realized by SPME-GC-FID method on a PDMS / DVB fiber. The BTEX and the styrene’s analysis was done by HS-trap-GC-FID method. These methods were validated in accordance with standard NF T 90-210 with a LQ less than the MCL. The volatile compounds in the bottled water and in the PET were analyzed by HS-trap-GC-MS method. The presence of FA, AA, DEP and BTEX in the bottled water with the PET was confirmed. It was highlighted that temperature and sun exposition influence the aldehydes’ migration. The acetaldehyde’s concentration after incubation at 40ºC wasn’t negligible and can modify the water’s organoleptic properties. The PET’s analyze reveals the presence of hydrocarbons, aldehydes, alcohols and ketones

Sammanfattning Sedan sjukdomen Covid-19s uppdykande i början av 2020 har forskning pågått för att karaktärisera sjukdomen ur alla tänkbara vinklar för att på kortast möjliga tid bereda väg för ett fungerande botemedel. Effektiva läkemedel som kan minska risken för allvarligt sjuka patienter att avlida i sjukdomen behövs; många preparat har föreslagits och testats och i Sverige har hittills två läkemedel godkänts för Covid-19. Ett av dessa är kortikosteroiden dexametason som godkänts för Covid-19-patienter i behov av syrgas eller respirator. Syftet med detta arbete var att undersöka hur effektiv kortikosteroidbehandling av svårt sjuka Covid-19-patienter var i jämförelse med standardbehandling utan kortikosteroider. En litteratursökning gjordes i PubMed och i covid-nma efter randomiserade kliniska studier av kortikosteroider jämfört med standardbehandling till patienter med Covid-19. Ur resultatet som inkluderade 7 kontrollerade studier med 7784 svårt sjuka patienter från 11 länder och fem kontinenter, gjordes en sammanvägning av den primära utfallsvariabeln mortalitet 28 dagar efter randomisering varpå relativ risk (RR) räknades ut individuellt per studie och sammanvägt för alla studier. Analysen gjordes också med den mest dominanta studien borträknad. Vidare utforskades möjliga samband mellan sjukdomsgrad och effektstorlek, dels genom ett försök till metaregression av studiemortalitet och andningshjälpsnivå mot RR som var inkonklusivt, men också genom att leta efter speciellt sjuka undergrupper i studierna. 3 studier rapporterade mortalitet efter 28 dagar, 1 studie rapporterade mortalitet efter 21 dagar, 2 studier rapporterade död på sjukhus och en studie rapporterade död efter 15 dagar. Testade preparat var dexametason, hydrokortison och metylprednisolon. Av 2885 patienter som randomiserats till någon kortikosteroid, dog 739, medan det av de 4899 som randomiserats till standardbehandling dog 1347 patienter vilket gav en icke signifikant RR på 0,93 (95% CI 0,86–1,01). Vid borträkning av den största studien som bestod av relativt friskare patienter erhölls en starkare och signifikant effekt med RR 0,80 (95% CI 0,70–0,92) baserat på 257 av 781 döda i steroidgrupperna jämfört med 237av 578 döda i någon kontrollgrupp med standardbehandling. Resultatet var även i linje med analysen av olika sjuka undergrupper från största studien som visade bäst effekt hos de med invasiv mekanisk andningshjälp (absolut riskreduktion 12,1%) samt en icke signifikant försämring hos de friskaste patienterna utan syrgasbehov. Sammantaget tyder dessa resultat på att behandling av svårt sjuka Covid-19-patienter med kortikosteroider minskar mortaliteten efter 28 dagar. Dessutom ger studien en stark indikation på att bästa effekten fås om kortikosteroiderna ges till patienter där den systemiska inflammationen i lungorna nått en gasutbyteshämmande nivå / ABSTRACT Since the emergence of the new corona virus disease, Covid-19, much research effort has gone into characterising every possible angle of the disease to pave the way for a possible cure in the shortest possible time. Effective therapies are needed that will reduce the risk of dying for severely to critically ill Covid-19 patients. Many existing therapies have been suggested, tested and repurposed for the treatment of Covid-19 but so far only two drugs have been approved in Sweden for this indication, namely the antiviral drug remdesivir and the corticosteroid dexamethasone. Corticosteroids are both immunosuppressive and anti-inflammatory and when they were administered previously for severe acute respiratory syndrome (SARS), middle east respiratory syndrome (MERS) and influenza they were found to increase the time to rid the body of virus. The purpose of this study was to investigate evidence found in the research literature of how effective corticosteroids are in reducing the risk of dying as compared to standard treatment with no corticosteroids when administered to hospitalised patients with severe Covid-19. A literature search was made in the PubMed and covid-nma databases for randomized clinical studies of corticosteroids versus standard treatment to patients with Covid-19. The result included 7 studies with 7784 patients from 11 countries and 5 continents which all reported death as an outcome in groups that were receiving corticosteroids compared to groups that were receiving standard care. The studies used one of the following corticosteroids as intervention: dexamethasone, methylprednisolone and hydrocortisone in different doses. In the groups receiving standard care, 1347 patients out of 4899 died while in the corticosteroid groups 739 of 2885 patients died. When doing a statistical calculation these figures indicated that the risk of dying when getting corticosteroids was 93% of the risk when not getting corticosteroids, however the difference was not statistically significant. After omitting the largest study from the material, that contributed the absolute majority of total participants, who were deemed relatively healthy or well taken care of, the results were instead that 257 out of 781 died in the steroid groups and 237 of 578 died in the control groups. This later comparison among supposedly sicker patients, gave a statistically significant 8,1% lower absolute risk of dying in the corticosteroid groups; an effect that could also be expressed as for every 25 patients treated, 2 more lives would be saved. A further control of a more severely sick subgroup of patients from the largest study, in need of invasive mechanical ventilation, revealed an absolute reduction of the risk of dying when given corticosteroids of 12,1%. This group showed the most effectful response to the administered corticosteroids in this study which could also be expressed as 1 more life saved for every 8 patients treated. Another sub group analysis of the patients from the largest study that were not in need of any type of oxygen support, indicated on the other hand a possible harm of corticosteroids. This potentially harmful effect was however not statistically significant. In summary, the results of this study imply that administration of corticosteroids to patients with severe Covid-19 will reduce the risk of dying. The greatest effect is seen in those patients that has reached a level of illness were the gas exchange in the lungs is impaired by the inflammation. Furthermore, caution must be taken not to introduce harm by giving corticosteroids to patients with milder disease in which the immunosuppressive properties of the drug could lead to unintended worsening of the illness.

Introduktion: Sjukvårdspersonal runt om i världen har stått på frontlinjen i stressiga arbetsmiljöer och tagit hand om COVID-19-patienter sedan SARS-CoV-2 förklarades som en global pandemi. Under pandemiska förhållanden står sjukvårdspersonal inför specifika utmaningar, där vissa leder till symptom på psykisk ohälsa. Statliga resurser till sjukvårdspersonal har ofta avsatts för kortsiktiga insatser. Långsiktiga investeringar med fokus på främjande av sjukvårdpersonalens psykiska hälsa behövs för att förhindra förvärrade folkhälsoproblem på grund av SARS-CoV-2. Syfte: Studiens syfte var att belysa hur sjukvårdspersonal rapporterar att deras psykiska hälsa påverkats av SARS-CoV-2-pandemin och vilka erfarenheter från tidigare interventioner för psykisk hälsa som skulle kunna vara användbara för att förbättra sjukvårdspersonals psykiska hälsa genom att belysa några exempel. Metod: En systematisk litteraturöversikt genomfördes, där 20 vetenskapliga artiklar inkluderades och analyserades med tematisk analys. Resultat: Totalt nio teman identifierades: psykisk ohälsa hos sjukvårdspersonal, SARS-CoV-2-pandemin, interventioner för psykisk hälsa, vårdkvalitet, säkerhetskultur, arbetsplatsbaserade tillvägagångssätt, mindfulness och konstaktivitetsmetoder, biomarkörbaserade tillvägagångssätt samt tekniska tillvägagångssätt. Viktiga fynd i denna litteraturöversikt är att teman säkerhetskultur och vårdkvalitet är associerade med de andra teman. Slutsats: När tillvägagångssätt implementeras i insatser för sjukvårdspersonals psykiska hälsa som främjar säkerhetskultur och vårdkvalitet främjar det också, enligt resultaten i denna översikt, långsiktiga effekter på individuell psykisk hälsa hos sjukvårdspersonal. Detta bör omedelbart beaktas av dem som utvecklar nya program för att främja psykisk hälsa för att stödja sjukvårdspersonal i effekterna av pandemin. / Introduction: Healthcare workers around the world have stood on the front lines in stressful work-environments, caring for COVID-19 patients since SARS-CoV-2 was declared a global pandemic. Under pandemic conditions healthcare workers face specific challenges, where some lead to symptoms of mental illness. Governmental resources to the healthcare workforce have often been allocated to short-term efforts. Long-term investments focusing on mental health promotion for HCW are needed to prevent worsening public health issues due to SARS-CoV-2. Aim: The aim of the study was to illuminate how HCW report that their mental health has been affected by the SARS-CoV-2 pandemic and what experiences from previous mental health interventions that may be useful in promoting HCW mental health by highlighting some examples. Methods: A systematic literature review was conducted, including 20 scientific articles analyzed with thematic analysis. Results: A total of nine themes were identified: mental distress in HCW, SARS-CoV-2 pandemic, mental health interventions, quality of care, safety culture, workplace-based approaches, mindfulness and art activity approaches, biomarker-based approaches as well as technology approaches. Important findings in this literature review are the themes safety culture and quality of care being associated with the other themes. Conclusion: When implementing approaches in mental health interventions for HCW that promote safety culture and quality of care, it also promotes, according to the findings in this review, long-term effects in individual mental health in HCW. This should be urgently taken into consideration by those developing new mental health promotion programs to support HCW in the effects of the pandemic.

Coronavirus disease 2019 (covid-19) är en smittsam infektionssjukdom som orsakas av viruset severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Sedan sjukdomens utbrott i december 2019 har viruset spridits globalt och infekterat fler än 270 miljoner människor världen över. Majoriteten av de som insjuknar i covid-19 får lindriga till måttliga besvär, men en liten del blir allvarligt sjuka och behöver sjukhusvård. Bland de patienter som blir allvarligt sjuka i covid-19 diagnostiseras en betydande del i det akuta skedet med sväljsvårigheter, eller dysfagi. Föreliggande studie bestod i en retrospektiv journalgranskning, som en del av ett kvalitetssäkringsarbete inom Region Gävleborg. Syftet med studien var att undersöka hur sväljsvårigheter kan manifesteras hos personer som vårdas på sjukhus till följd av covid-19 och som remitterats till logoped för bedömning och åtgärder. 60 deltagare inkluderades i studien, varav 17 var kvinnor och 43 var män. Resultaten visar att förekomsten av dysfagi var hög i det akuta skedet, där 42 deltagare (70 %) bedömdes ha dysfagi vid första logopedbedömning. Många deltagare återhämtade sig från sin dysfagi under vårdtiden, men 12 deltagare (20 %) hade kvarstående dysfagi vid utskrivning. Behovet av nutritionsstöd och andningsstöd under vårdtiden var stort. Vanliga fynd under de kliniska sväljbedömningarna var hosta, trögutlöst sväljning och nedsatt oral bearbetning. Deltagarna erhöll logopediska rekommendationer främst gällande anpassad kost, sittställning och munvård. Deltagarnas sväljförmåga skattades med Functional Oral Intake Scale (FOIS) vid första logopedbedömning och vid utskrivning. Vid första bedömning rekommenderades en majoritet av deltagarna anpassad kost (FOIS 1–6) och medelvärdet för FOIS var 3,5 ± 2,1. Vid utskrivning hade de flesta återgått till normalkost (FOIS 7) och medelvärdet för FOIS var 6,0 ± 1,8 (p < 0,001). Denna studie visar att en majoritet av de som vårdats på sjukhus till följd av covid-19 i Region Gävleborg och som remitterats till logoped, uppvisade dysfagi i det akuta skedet men kunde vid utskrivning äta normalkost. Behovet av mer forskning och vidare analyser av hur sväljsvårigheter manifesteras och upplevs hos patientgruppen är fortsatt stort. / Coronavirus disease 2019 (COVID-19) is a contagious infectious disease caused by the virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the outbreak in December of 2019, the virus has spread globally and infected more than 270 million people worldwide. The majority of people infected with COVID-19 will have mild to moderate symptoms, but some will suffer from severe illness which requires hospital care. Many of those who experience severe illness from COVID-19 are diagnosed with swallowing difficulties, or dysphagia, in the acute stage. This study consisted of a retrospective medical chart review and is part of a review of quality control in Region Gävleborg. The aim of the study was to investigate how swallowing difficulties manifest in people who require hospital care due to COVID-19 and who have been referred to the Speech and Language Therapy department. 60 participants were included in the study, of whom 17 were women and 43 were men. The results show that the prevalence of dysphagia was high in the acute stage, where 42 participants (70%) were diagnosed with dysphagia during the first SLT assessment. Many participants recovered from their dysphagia during their hospital stay, but 12 participants (20%) had persistent dysphagia at discharge. The need for nutritional and respiratory support was high. Common findings from the clinical swallowing assessments were coughing, difficulty initiating swallowing as well as affected oral processing. Common SLT recommendations included modified consistencies, posture and oral care. Swallowing ability was graded with the Functional Oral Intake Scale (FOIS) at first SLT assessment and at discharge. At first SLT assessment a majority of the participants were recommended a modified diet (FOIS 1-6) and the average FOIS was 3.5 ± 2.1. At discharge most participants had returned to a normal diet (FOIS 7) and the average FOIS was 6.0 ± 1.8 (p < 0,001). This study shows that a majority of the people who were hospitalized due to COVID-19 in Region Gävleborg and who were referred for an SLT evaluation, had dysphagia in the acute stage and recovered from their swallowing difficulties before discharge. More research and further analyses of how swallowing difficulties manifest in patients hospitalized due to COVID-19 is still needed.

Contexte : Partout dans le monde, la population âgée en hébergement a été la plus lourdement affectée par la pandémie de COVID-19, du point de vue des infections et des décès. Or, ces mêmes personnes ont été exclues d’une grande partie de la littérature scientifique. Ce mémoire décrit l’évolution des éclosions dans 17 CHSLD publics de Montréal, dont certains ont été fortement atteints alors que d’autres ont été épargnés pendant la première vague (23 février au 11 juillet 2020), en cherchant à élucider les facteurs associés à l’incidence et à la létalité de la COVID-19. Méthodes : Des données institutionnelles ont été recueillies sur les 17 CHSLD du CIUSSS Centre-Sud-de-l'Île-de-Montréal et des données individuelles ont été obtenues grâce à une révision des 1197 dossiers de patients atteints de la COVID-19 en première vague. Dans l’analyse ARIMA, des séries chronologiques ont été construites pour les cas incidents bruts chez les résidents en CHSLD et dans la ville de Montréal, afin d’évaluer l’impact de deux interventions, soit le port généralisé du masque de procédure et le dépistage élargi des résidents et des employés. Dans l’analyse des infections par CHSLD, des modèles de régression de type binomial négatif ont été construits pour estimer l’effet des facteurs de risque institutionnels sur l’incidence de la COVID-19 chez les résidents. Dans l’analyse de surmortalité, les excès de décès durant la période de février à juillet ont été évalués avec des tests t et des ratios de taux entre l’année 2020 et la moyenne des quatre années précédentes (2016-2019). Enfin, pour l’analyse de mortalité dans la cohorte rétrospective de résidents atteints de la COVID-19, des modèles de régression logistique à effets mixtes ont été utilisés pour évaluer les facteurs institutionnels et les traitements associés à la mortalité dans les 30 jours suivant un diagnostic de COVID-19, en contrôlant pour les facteurs de risque individuels. Résultats : Dans l’analyse de série chronologique ARIMA, chaque augmentation d’un cas incident quotidien par 100 000 à Montréal était associée avec une augmentation de 0,051 (IC95% 0,044 à 0,058) fois l’incidence quotidienne en CHSLD la semaine suivante, chez les résidents à risque. De plus, en contrôlant pour la transmission communautaire, chaque palier d’intensification du dépistage était associé à une diminution de l’incidence de 11,8 fois (IC95% -15,1 à -8,5) dans les deux semaines suivantes, chez les résidents à risque. Dans le modèle explicatif des infections au niveau des CHSLD, la pénurie sévère d’infirmières auxiliaires (IRR 3,2; IC95% 1,4 à 7,2), la mauvaise performance aux audits ministériels (IRR 3,0; IC95% 1,1 à 7,8) et un score moyen d’autonomie plus faible (IRR 2,1; IC95% 1,4 à 3,1) étaient associés au taux d’incidence par centre. En revanche, la présence de zone chaude dédiée aux patients COVID-19 (IRR; 0,56 IC95% 0,34 à 0,92) était protectrice. Pour l’ensemble des 17 CHSLD avec 2670 lits, l’excès de décès de février à juillet 2020 était de 428 (IC95% 409 à 447). Comparé aux quatre années précédentes, il y a eu plus que le double (IRR 2,3; IC95% 2,1 à 2,5) de décès en 2020 pendant la période de la première vague. Pour 12 CHSLD qui ont vécu des éclosions importantes, les excès de décès en 2020 variaient de 5,2 à 41,9 décès par 100 lits, avec une surmortalité par rapport aux années précédentes allant de 1,9 à 3,8. Selon l’analyse de mortalité dans la cohorte rétrospective, les facteurs individuels associés à la mortalité dans les 30 jours suivant le diagnostic de COVID-19 étaient l’âge (OR 1,58; IC95% 1,35 à 1,85 par tranche additionnelle de 10 ans), le sexe masculin (OR 2,37; IC95% 1,70 à 3,32), la perte d’autonomie (OR 1,12; IC95% 1,05 à 1,20 pour chaque augmentation d’un point à l’Iso-SMAF), le niveau d’intervention médicale C (OR 3,43; IC95% 1,57 à 7,51) et D (OR 3,61; IC95% 1,47 à 8,89) comparé au niveau A, ainsi que les diagnostics de trouble neurocognitif (OR 1,54; IC95% 1,04 à 2,29) et d’insuffisance cardiaque (OR 2,36; IC95% 1,45 à 3,85). Le traitement avec une thromboprophylaxie (OR 0,42; IC95% 0,29 à 0,63) et l’infection tardive après le 20 avril 2020 (OR 0,46; IC95% 0,33 à 0,65) étaient associés à la survie à 30 jours. Pour les facteurs institutionnels, la pénurie sévère de 25% ou plus d’infirmières auxiliaires (OR 1,91; IC95% 1,14 à 3,21 par rapport à une pénurie légère < 15%) et la taille du centre (OR 1,77; IC95% 1,17 à 2,68 pour chaque 100 lits additionnels) étaient associés au décès dans les 30 jours. Conclusion : Ce mémoire a relevé plusieurs facteurs de risque modifiables au niveau institutionnel associés aux infections et aux décès COVID-19, dont le dépistage, l’adhérence aux directives ministérielles de prévention et contrôle des infections, la pénurie d’infirmières auxiliaires et le nombre de lits par centre. Ces enjeux cruciaux devront être au cœur des futures orientations et politiques touchant les centres d’hébergement, pour cette pandémie et au-delà. / Background: In the midst of the COVID-19 pandemic, the population of long-term care residents has been the hardest hit by infections and deaths all around the world. Yet, these same individuals have been excluded from vast segments of the scientific literature. This thesis describes the evolution of outbreaks in 17 public long-term care facilities (“CHSLD”) in Montreal, some of which were severely affected and others were relatively spared during the first wave (February 23 to July 12, 2020), in search of risk factors associated with COVID-19 cases and deaths. Methods: Institutional-level data on the 17 CHSLDs were collected from relevant administrative departments within the establishment (CIUSSS Centre-Sud-de-l'Île-de-Montréal), and individual-level data was obtained from the chart reviews of 1,197 first wave COVID-19 patients. For the ARIMA analysis, time series were built using the crude incidence rates among CHSLD residents and in the city of Montreal, in order to assess the impact of two interventions – introduction of the mask-wearing policy and generalized testing among residents and staff. For the analysis of facility-level infection rates, negative binomial regression models were built to estimate the effects of several institutional risk factors on incident cases. As for the excess mortality analysis, excess death and relative mortality were estimated using one-sample t-tests and rate ratio tests to compare 2020 deaths with average deaths in the previous four years (2016-2019), for the period of February to July. Lastly, for the survival analysis of the retrospective cohort, mixed-effects logistic regression models were used to identify institutional factors and treatments associated with 30-day mortality after a COVID-19 diagnosis, while controlling for individual risk factors. Results: In the ARIMA time series analysis, each additional case per 100,000 per day in Montreal was associated with a 0.051 (95%CI 0.044 to 0.058) increase in CHSLD daily incidence a week later, among at-risk residents. In addition, while controlling for community transmission, increased testing intensity was associated with a 11.8 (95%CI -15.1 to -8.5) decrease in CHSLD daily incidence two weeks later, among at-risk residents. In the negative binomial regression model for facility-level COVID-19 infections, poor performance on ministry audits (IRR 3.0 95%CI 1.1 to 7.8), severe shortage of auxiliary nurses (IRR 3.2 95%CI 1.4 to 7.2) and lower average autonomy scores (IRR 2.1 95%CI 1.4 to 3.1) were associated with incident cases, while the presence of a COVID-19 unit or “red zone” (IRR 0.56 95%CI 0.34 to 0.92) was inversely associated with infections. For the 17 CHSLDs, excess deaths from February to July 2020 was 428 (95%CI 409 to 447). Compared to the same period in the previous four years, 2020 mortality during the first wave was 2.3 (IRR 95%CI 2.1 to 2.5) times higher. For a subset of 12 facilities that experienced substantial outbreaks, excess deaths in 2020 varied from 5.2 to 41.9 deaths per 100 beds, with significant excess mortality between 1.9 and 3.8, relative to previous years. According to the mortality analysis by mixed-effects logistic regression, individual risk factors associated with 30-day mortality after a COVID-19 diagnosis were age (OR 1.58 95%CI 1.35 to 1.85 per additional 10 years), male sex (OR 2.37 95%CI 1.70 to 3.32), loss of autonomy (OR 1.12 95%CI 1.05 to 1.20 per unit increase of Iso-SMAF profile), C-level (OR 3.43 95%CI 1.57 to 7.51) or D-level (OR 3.61 95%CI 1.47 to 8.89) medical intervention compared to A-level, as well as being diagnosed with a neurocognitive disorder (OR 1.54 95%CI 1.04 to 2.29) or congestive heart failure (OR 2.36 95%CI 1.45 to 3.85). Treatment with thromboprophylaxis (OR 0.42 95%CI 0.29 to 0.63) and diagnosis after April 20, 2020 (OR 0.46 95%CI 0.33 to 0.65) were associated with 30-day survival. As for institutional risk factors, severe shortage of auxiliary nurses (OR 1.91 95%CI 1.14 to 3.21) and facility size (OR 1.77 95%CI 1.17 to 2.68 per 100 beds) increased the odds of dying within 30 days. Conclusion: This study identified several modifiable risk factors at the institutional level associated with COVID-19 infections and deaths, including testing strategies, adherence to ministry directives for infection prevention, auxiliary nurse shortages, and number of beds per facility. Future policies and regulations targeting long-term care facilities will need to tackle these critical issues, for this pandemic and beyond.