All cells depend on properly folded proteins for survival and function. Misfolding of proteins results in loss of critical functions and may trigger the misfolding of other nearby proteins leading to toxic aggregation. While many proteins can fold on their own, others with complicated domain structures require assistance from protein folding machines called chaperones. The most complex and highly specialized of all chaperones is the eukaryotic chaperonin complex CCT which is necessary for the folding of a wide variety of essential proteins. These include the cytoskeletal proteins actin and tubulin as well as the Gβ subunit of the G protein heterotrimer. However, CCT activity can also drive diseases such as cancer and viral infections and could represent a high value therapeutic target if the mechanisms by which it folds its different client proteins were better understood. To this end, we identified and characterized an interaction between CCT and the RNA-dependent RNA polymerase of SARS-CoV-2, the virus responsible for the deadly global pandemic that began in 2019. We showed that SARS-CoV-2 replication is impaired by loss of CCT and that the polymerase, designated Nsp12, interacts with CCT upon synthesis and quickly releases - the hallmark pattern of a CCT substrate. Furthermore, we solved a 3.3 Å cryo-EM structure of Nsp12 bound to open CCT showing Nsp12 binding between the two rings of CCT and extending up through of the folding chambers and out of CCT. At 107 kD, Nsp12 is the largest substrate ever visualized inside of CCT and answers a long-standing question in the field of how CCT could accommodate substrates larger than its 70 kD folding chamber. Given that CCT is known to fold proteins with WD40-repeat domains, we also investigated a potential relationship between CCT and RPE65. RPE65, which contains a WD40 domain, is the retinyl ester isomerase that converts all-trans retinyl esters into 11-cis retinol, a key step in the visual cycle, and its mutation is a common cause of hereditary retinal dystrophies. We showed that CCT interacts with RPE65 and that nascent RPE65 binds and releases from CCT albeit with relatively slow kinetics. However, RPE65 is not dependent on CCT for expression or activity. This suggests that the relationship between RPE65 and CCT may represent a novel CCT function distinct from the canonical obligate substrate dynamic.

Antimicrobial resistance (AMR) threatens our modern standard of living with the potential return to a pre-antibiotic condition where deadly infections are no longer treatable. Wastewater treatment plants (WWTPs) are vital components in water sanitation infrastructure and are now also being recognized as valuable monitoring points for antibiotics, antibiotic resistant bacteria (ARB), and antibiotic resistance genes (ARGs) disposed of or excreted by human populations. Hospital waste water is of special interest as a potential focused monitoring point and in general research is needed to establish the benefits of both on-site and community-scale wastewater treatment as important barriers to the disseminators of ARGs into the environment. The research aims described herein examine these components of wastewater treatment and how they relate to AMR indicators identified through metagenomic sequencing. Through monitoring of local WWTPs, it was found that AMR indicators shifted over time and in relation to human behavior that changed due to the COVID-19 pandemic. Hospital wastewater did not measurably impact the microbiome during simulated activated sludge wastewater treatment according to broad-scale metagenomic ARG profiling; however, some clinically-relevant ARGs escaped treatment. Lastly, a study of a transect of WWTPs indicated impacts on the abundance of certain ARGs in downstream riverine receiving environments. Nonetheless, there appeared to be a number of other factors at play, and upstream and downstream resistomes tended to remain similar, calling for further research to delineate impacts of various wastewaters and treatments on ARGs in affected aquatic environments. / Doctor of Philosophy / Antimicrobial resistance (AMR) occurs when bacteria, viruses, and fungi are able to survive in the presence of antibiotics because they carry antibiotic resistance genes (ARGs) encoded in their DNA. AMR is a major public health concern as it makes it so that antibiotics are no longer effective against potentially deadly infections. Wastewater treatment plants (WWTPs) are being discovered as a hub of opportunity for monitoring potential AMR problems in a community. WWTPs receive sewage from homes and various industries. This sewage contains rich information for researchers to examine in terms of which antibiotics, bacteria, and ARGs are circulating in the community. This makes it possible to find out which antibiotics are being consumed in the community and which ARGs might be prevalent. The purpose of this research was to better understand both how WWTPs can be used as monitoring points for AMR and how they can be improved to help reduce ARGs emitted to rivers and streams where treated water is discharged. It was found that the types of ARGs prevalent in wastewater changed over time, especially during the COVID-19 pandemic as people worked from home and changed habits regarding doctors' visits, which impacted antibiotic use. Hospital sewage was studied as a useful indicator of pathogens and ARGs that are challenging a community and also the antibiotics being used. This research explored what happened to ARGs during the treatment of domestic (i.e., from people's homes) wastewater along with hospital wastewater and found that hospital wastewater introduced some ARGs that are typically found in clinical settings, but did not negatively impact the overall wastewater treatment process. Finally, the impact that WWTPs have on rivers to which treated water is discharged was explored. The results indicated that certain ARGs were elevated downstream of the WWTPs. However, when examining all ARGs together, no major shifts due to the treated wastewater were apparent.

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.

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.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 as a highly infectious virus that spread rapidly and was declared a pandemic by the World Health Organization (WHO) in March of 2020.1 SARS-CoV-2 infection causes respiratory disease (Coronavirus Disease; COVID-19), and during the initial infection wave of the pandemic, disease severity ranged from asymptomatic to mild upper respiratory disease, to severe pneumonia resulting in hospitalization and death.1 To date, over 750 million cases of COVID-19 and almost 7 million deaths due to the disease have been confirmed (WHO COVID-19 Dashboard). Virus-like particles are nanoparticles made up of existing viral structural proteins that will assemble into a particle form. The hepatitis B virus core antigen (∆HBcAg) is a stable VLP that will maintain its ability to fold into a viral particle following incorporation of foreign epitopes into its protein sequence. In this project, we produced a vaccine against SARS-CoV-2 that was composed of three SARS-CoV-2 Spike protein epitopes inserted into the ∆HBcAg VLP. These insertions included Spike epitopes predicted to induce a humoral and/or cell-mediated immune response. The immunogenicity of the resultant vaccine was tested utilizing a K18-hACE2 transgenic C57BL/6 mouse model. Mice were challenged with live SARS-CoV-2 three weeks after the final booster dose and the vaccine was evaluated for protective efficacy. Results of these studies showed epitope-specific humoral and cell-mediated immune responses, but these responses were insufficient in protecting against SARS-CoV-2 infection. / Doctor of Philosophy / Coronaviruses have caused gastrointestinal and respiratory disease in humans and a variety of veterinary species for decades. In response to the onset of the COVID-19 (Coronavirus Disease) pandemic in late 2019, we created a vaccine against the virus that causes this disease: the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 infects human cells by attaching via one of its surface proteins (the Spike protein) to the human ACE2 receptor (angiotensin converting enzyme 2). After this binding occurs, the virus can enter the cell and begin to replicate, resulting in cellular damage, organ-level dysfunction, and clinical disease. An effective vaccine against SARS-CoV-2 would induce antibodies that bind to this Spike protein, thereby blocking its ability to infect host cells and preventing the downstream effects of infection. Our vaccine consisted of a protein from the hepatitis B virus (∆HBcAg), which naturally folds into a virus-like particle (VLP). This VLP can be used as a stable backbone and foreign epitopes can be inserted into the particle for presentation to the immune system as a vaccine. We inserted three SARS-CoV-2 Spike protein epitope into the ∆HBcAg backbone and tested the vaccine's ability to elicit an immune response and protect against infection with live SARS-CoV-2. Results from these studies showed an antibody response to the vaccine and higher levels of anti-viral cytokines in vaccinated mice compared to controls, but incomplete protection against disease. Additionally, we identified areas for vaccine optimization that will inform future studies utilizing this type of vaccine platform.

Yes

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.

[pt] A pandemia do COVID-19 teve impactos sem precedentes em indivíduos e comunidades em todo o mundo. Uma questão de grande preocupação é o impacto da pandemia na saúde mental. O isolamento, o medo e a incerteza causados pelo vírus levaram ao aumento das taxas de ansiedade, depressão e outros problemas de saúde mental. As preocupações com o aumento da prevalência de distúrbios psicológicos já estão levando os países a incluir a saúde mental e o apoio psicossocial em seus planos de resposta à COVID-19, mas, apesar disso, permanecem grandes lacunas e preocupações. Os múltiplos estressores desencadeados pelo vírus, somados às graves interrupções nos serviços públicos, deixaram sérias lacunas no atendimento de quem mais precisa. Além do agravamento e generalização de condições de saúde mental pré-existentes, agora também há a necessidade de acomodar questões recém-desenvolvidas. Nosso objetivo é, portanto, investigar os principais motivos que levaram os pacientes do Serviço de Psicologia Aplicada da PUC-Rio a buscar tratamento psicológico antes (2019) e durante a pandemia (2020 e 2021). Através de uma análise lexical dos formulários de demanda psicológica, pretendemos rastrear as possíveis transições e agravos entre demandas psicológicas de adultos (artigo 1) e famílias (artigo 2) utilizando o software IRaMuTeQ e o método Reinert, que analisa qualitativa e quantitativamente as transcrições relatórios. Por meio desse recurso de análise, é possível começar a mapear e investigar as queixas subjetivas desses pacientes, sua evolução e suas correlações. / [en] The COVID-19 pandemic has had unprecedented impacts on individuals and communities around the world. A matter of great concern is the impact of the pandemic on mental health. The isolation, fear and uncertainty caused by the virus has led to increased rates of anxiety, depression and other mental health issues. Concerns about the increasing prevalence of psychological disorders are already leading countries to include mental health and psychosocial support in their COVID-19 response plans, but despite this, major gaps and concerns remain. The multiple stressors triggered by the virus, in addition to the severe interruptions in public services, have left serious gaps in the care of those who need it most. In addition to the worsening and generalization of pre-existing mental health conditions, there is now also a need to accommodate newly developed issues. Our objective is therefore to investigate the main reasons that led patients from the Service of Applied Psychology at PUC-Rio to seek psychological treatment before (2019) and during the pandemic (2020 and 2021). Through a lexical analysis of the psychological demand forms, we intend to trace the possible transitions and aggravations between psychological demands of adults (article 1) and families (article 2) using the IRaMuTeQ software and the Reinert method, which qualitatively and quantitatively analyzes the transcribed reports. Through this analysis resource, it is possible to start mapping and investigating the subjective complaints of these patients, their development and their correlations.