How do bacteria grow and replicate rapidly? How do viruses and phages adapt to their host environments? Bacteria require efficient translation to grow and replicate rapidly, and translation is often rate-limited by initiation. A feature that is conserved across bacterial lineages is the Shine-Dalgarno (SD) sequence at the mRNA 5’ UTR, which pairs with the anti-SD sequence located at the 3’ end of mature 16S rRNA. Nonetheless, much about this interaction remains unclear. Chapter 2 reveals evolutionary differences between Cyanobacteria and chloroplast translation initiation using a new model (DtoStart) that better define optimal SD sequence and an RNA-Seq-based approach that reliably characterize the 3’ end of mature 16S rRNAs. Efficacy of translation elongation depends much on tRNA-mediated codon adaptation. In Escherichia coli, selection favours major codons because they are rapidly decoded by abundantly available cognate tRNAs. Nonetheless, the degree codon bias correlates with tRNA availability is unclear in many bacterial species because tRNA abundance is often inadequately approximated by gene copy numbers. To better understand tRNA-mediated codon bias, Chapter 3 describes an RNA-Seq-based approach to robustly quantify tRNA abundance. Finally, Chapter 4 evaluates the degree optimal translation initiation and elongation signals affect ribosome dynamics. The emergence of COVID-19 pandemic poses a serious global health emergency. To establish infection during cell entry, the coronavirus Spike protein binds to the host ACE2 receptor, and a high binding potential between these two players is key to infectivity. While SARS-CoV-2 transmits efficiently in humans, it is less clear which other mammals are at risk of being infected. Chapter 5 investigates the host range of SARS-CoV-2 through comparative sequence analyses at the ACE2 receptors and the Spike proteins. As obligate parasites, coronaviruses regularly infect host tissues that express antiviral proteins (AVPs) in abundance and must evade or adapt to the host cellular environments post-entry. Two AVPs that shape viral genomes are ZAP that binds to CpG dinucleotides to facilitate viral transcript degradation, and APOBEC3 which deaminates C into U leading to dysfunctional transcripts. Chapter 6 shows that coronavirus genomes are CpG deficient to evade ZAP and are subjected to constant C to U deamination by APOBEC3. This thesis examines two key concepts of microbial genome evolution: 1) coevolution between gene features and the translation machinery in bacteria, and 2) adaptation of viruses to the hosts they infect. Chapters 2, 3, and 4 are aimed at improving our understanding in bacterial gene expression in the applications of transgenic biosynthesis and phage therapy. Chapters 5 and 6 are aimed at improving our understanding in the origin and evolution of SARS-CoV-2 and our ability to control the spread of infection.

Bakgrund: Covid-19 pandemin har orsakat ett stort antal dödsfall globalt och bidragittill ökade sjukhusinläggningar. Pandemin har ökat belastningen på sjukvården vilket har resulterat i att sjuksköterskor har fått arbeta under andra förhållanden och villkor. Studier från tidigare epidemier har visat att sjuksköterskor upplevt otillräcklighet till patienter samtidigt som stark gemenskap till kollegor funnits.Syfte: Att beskriva sjuksköterskors upplevelser av arbetet med Covid-19 vård inom slutenvården.Metod: En litteraturöversikt baserad på artiklar med kvalitativ design genomfördes.13 artiklar valdes ut till resultatet och analyserades med hjälp av Fribergs (2017)struktur.Resultat: Sjuksköterskor har upplevt brist på kunskap kring den nya sjukdomen, hur skyddsutrustningen skulle tillämpas och vilket skydd den hade. Flertalet sjuksköterskor har upplevt rädsla över att bli smittade av viruset. Sjuksköterskor upplevde även psykologiska och fysiologiska besvär gällande anpassningen till en ny vårdmiljö samt användningen av skyddsutrustning.Slutsats: Förlängda arbetstider, nya rutiner, ny form av isoleringsvård, nya arbetsplatser samt bristande kunskap kring sjukdomen genererade i fysiska ochpsykiska besvär för sjuksköterskor. En ny och förändrad vårdsituation bidrog till att personcentrerad- och säkervård var bristande under pandemin. Trots lärdomar från tidigare epidemier kvarstår bristande kunskap kring vård vid infektionssjukdomar.Nyckelord: Erfarenheter, personcentrerad vård, Sars-Cov-2, sjuksköterskor, säker vård / Title: Exhausted by the fear of Covid-19. A literature review of qualitative design about nurses ´experiences of the work with Covid-19 in inpatient care.Background: The Covid-19 pandemic has caused large frequency of deaths globallyand has led to increased hospitalizations. The pandemic has increased the burden on healthcare and due to that, nurses have had to work under new working conditions. Studies from earlier epidemics have shown that nurses have felt insufficient for patients in while at the same time felt a strong solidarity to colleagues.Aim: To describe nurses’ experiences of working with Covid-19 care in inpatient care.Method: A literature review with qualitative design was done. 13 articles were selected for the result and were analyzed with help from Friberg (2017) structure.Results: Nurses have experienced lack of knowledge regarding the new disease and the usage of protective equipment as well as it´s protectionary level. A majority of nurses have also experienced a fear of getting infected of the virus themselves. Nursesalso suffered from psychological and physical inconvenience from the adaptation of a new care environment with a mandatory usage of protective equipment.Conclusion: Extended working hours, new routines, new form of insulation care and lack of knowledge generated physical and psychological inconvenience for nurses. A new and changed work situation contributed to the lack of person-centered and secure care during the pandemic.Despite lessons learned from earlier epidemics, there is still lack of knowledge about care of infectious diseases.Keywords: Experiences, person-centered care, registered nurses, safe care, Sars-Cov-2

Chloroquine (CQ) and hydroxychloroquine (HCQ) have been proposed as treatments for COVID-19. These drugs have been studied for many decades, primarily in the context of their use as antimalarials, where they induce oxidative stress-killing of the malarial parasite. Less appreciated, however, is evidence showing that CQ/HCQ causes systemic oxidative stress. In vitro and observational data suggest that CQ/HCQ can be repurposed as potential antiviral medications. This review focuses on the potential health concerns of CQ/HCQ induced by oxidative stress, particularly in the hyperinflammatory stage of COVID-19 disease. The pathophysiological role of oxidative stress in acute respiratory distress syndrome (ARDS) has been well-documented. Additional oxidative stress caused by CQ/HCQ during ARDS could be problematic. In vitro data showing that CQ forms a complex with free-heme that promotes lipid peroxidation of phospholipid bilayers are also relevant to COVID-19. Free-heme induced oxidative stress is implicated as a systemic activator of coagulation, which is increasingly recognized as a contributor to COVID-19 morbidity. This review will also provide a brief overview of CQ/HCQ pharmacology with an emphasis on how these drugs alter proton fluxes in subcellular organelles. CQ/HCQ-induced alterations in proton fluxes influence the type and chemical reactivity of reactive oxygen species (ROS).

En global pandemi orsakat av viruset Covid-19 har lamslagit samhället och sjukvården sedan senhösten 2019. Sjuksköterskor världen över har vittnat om en påfrestande arbetssituation. Tidigare forskning redovisar att arbetsmiljö har en stor påverkan på fysisk och psykisk hälsa för personal inom hälso- och sjukvården. Syftet är en systematisk litteraturöversikt vilken syftar till att beskriva hur sjuksköterskor har upplevt att arbeta med patienter smittade med Covid-19. Resultatet utgår från tio artiklar med både kvalitativ och kvantitativ ansats och presenteras i tre huvudkategorier och sju subkategorier. I resultatet framkommer att sjuksköterskor har haft en arbetsmiljö där oklara rutiner, information och kommunikation tillsammans med smitta, smittspridning och skyddsutrustning samt hög arbetsbelastning och låg grad av återhämtning ledde till negativa psykiska konsekvenser i form av stress, ångest, oro, rädsla med mera. I vissa fall blev konsekvenserna psykisk ohälsa i form av PTSD eller depression. Sjuksköterskorna upplevde också en ökad känsla av fokus i samhället och en stolthet över sitt yrke och gemenskap i sitt arbetsteam i en svår situation. Vikten av stöd framkom tydligt, både som strategier för egenstöd och stöd från chef och samhälle. Psykologiskt stöd och krisstöd samt en anpassning av arbetsrutiner och arbetsmiljö föreslås som implikationer i framtidens sjukvård inför eventuella krissituationer för att vara bättre rustade.

SARS-CoV-2 is the virus responsible for the current global pandemic, COVID-19. Because this virus is novel, little is known about its sensitivity to disinfection. In this study, we performed suspension tests against SARS-CoV-2 using three commercially available quaternary ammonium compound (Quat) disinfectants and one laboratory-made 0.2% benzalkonium chloride solution. Three of the four formulations completely inactivated the virus within 15 seconds of contact, even in the presence of a soil load or when diluted in hard water. We conclude that Quats rapidly inactivate SARS-CoV-2, making them potentially useful for controlling SARS-CoV-2 spread in hospitals and the community. In addition to disinfection, little is known about the sensitivity of SARS-CoV-2 to wastewater. A number of researchers have tracked the spread of COVID-19 by using qPCR to look for SARS-CoV-2 RNA in wastewater, but it is unclear how long that RNA lasts or whether that RNA is from intact or inactivated virus. In this study, we added laboratory-grown SARS-CoV-2 to various samples of wastewater and measured its persistence using both qPCR, which detects all viral RNA, and a plaque assay, which detects only infectious virus. The level of infectious virus declined sharply by over 4 log reductions during an 8 day time period, while the level of measurable RNA did not decline significantly. Autoclaving or filtering the wastewater before adding virus attenuated this effect, producing declines of only around 1-3 logs for the infectious virus over 8 days and no significant decline for the RNA.

The aim of this study was to assess the prevalence and predictive factors of secondary infectionsin patients with coronavirus disease 2019 (COVID-19) and compare with influenza. A retrospective cohort study which included COVID-19 and influenza patients with samples processed at Karolinska University Hospital Laboratory between 1st March 2020 to 1st January2021 and 1st January 2015 to 1st January 2021 respectively. Blood, urine and respiratory culture results from 7 days before and 7 days after the primary diagnosis collected from laboratory information system. Chi-square and Mann-Whitney U test used for descriptive comparison. Predictive factors of secondary infections analyzed using logistic regression. Data includes 16,354 patients:7470 COVID-19 and 8884 influenza. Secondary infections were significantly fewer in COVID-19 patients (26.6%) compared to influenza patients (30%) p<0.01. Lower proportion of episodes with growth (EWG) in blood culture of COVID-19 patients (1.8%) compared to influenza (2.9%) p<0.001. Lower proportion of EWG in respiratory tract cultures of COVID-19 patients (11.1%) compared to influenza patients (24.5%) p<0.001. Higher proportionof EWG in urinary tract cultures of COVID-19 patients (24.5%) compared to influenza (20.1%)p<0.001. Staphylococcus aureus were common bacteria in blood and respiratory tract in both cohorts. Escherichia coli were the most common bacteria in urine in both cohorts. Fungi were least common with unspecified yeast being the most frequent. Likelihood of secondary infection lower in males compared to females AOR 0.70 (95%CI 0.66-0.76)), lower in other clinicalsettings AOR 0.65 (95%CI 0.56-0.76) and increased with age in both COVID-19 and influenza patients (AOR 1.03(95%CI 1.02-1.04)). Higher probability of secondary infections in young influenza patients compared to young COVID-19 patients. A lower prevalence of secondary infections in blood, respiratory tract cultures of COVID-19 patients compared to influenza. Olderage, female sex, intensive care were predictive factors for secondary infections. Findings important for planning of treatment protocols.

Background SARS-CoV-2 is the virus responsible for the current global pandemic, COVID-19. Because this virus is novel, little is known about its sensitivity to disinfection. Methods We performed suspension tests against SARS-CoV-2 using three commercially available quaternary ammonium compound (Quat) disinfectants and one laboratory-made 0.2% benzalkonium chloride solution. Findings Three of the four formulations completely inactivated the virus within 15 s of contact, even in the presence of a soil load or when diluted in hard water. Conclusion Quats rapidly inactivate SARS-CoV-2, making them potentially useful for controlling SARS-CoV-2 spread in hospitals and the community.

Enligt Socialstyrelsen (2020) anses hedersrelaterat våld vara ett allvarligt samhällsproblem i Sverige och enligt bland annat Grzyb (2016) ett socialt problem globalt. En av de särskilt sårbara grupperna som kan utsättas för det hedersrelaterade våldet är hbtqi+-personer (Regeringskansliet, 2021) där denna grupp bland annat kan utsättas för tvångsäktenskap, korrigeringsresor och omvändelseförsök (RFSL, 2018). Syftet med denna studie är att undersöka och analysera hur SARS-CoV-2 pandemin kan ha påverkat en grupp socionomer i sitt arbete med hedersrelaterat våld och förtryck riktat till hbtqi+-personer samt om det kan finnas kunskaps- och rutinbrister i den aktuella verksamheten. Ytterligare ett syfte är att försöka sammanfoga dessa två komplexa områden och se på vilket sätt man försöker arbeta med detta inom ramen för det sociala arbetet. Informanterna som intervjuades i denna studie representerar sig själva i den verksamhet där de jobbade. Den information som vår studie fick ta del av från informanterna var endast aktuell vid tidpunkten för studien. Tjugotre kommuner i Sverige tillfrågades om att delta i studien varav tre kommuner ville delta och de resterande tjugo kommunerna ville av olika anledningar inte delta eller återkopplade inte angående medverkan. En kvalitativ metod har använts för genomförande av studien. Semistrukturerade intervjuer genomfördes med tre informanter som jobbade med våld där bland annat hedersrelaterat våld riktat till hbtqi+-personer innefattades. Vidare har en tematisk analysmetod tillämpas för analys av insamlat data. I resultatet framkommer det bland annat att pandemins isolering kan ha begränsat hbtqi+-personers rörelsefrihet vilket även kan ha påverkat yrkesverksammas arbete och att verksamheter i Sverige till viss del präglas av kunskap men även till stor del av behov av kunskapsutveckling i hur verksamheterna ska stötta och skydda hbtqi+-personer som kan befinna sig i en hederskontext. En av studiens viktigaste slutsatser är att beakta hur maktordningar samverkar där individer som är utsatta för hedersrelaterat våld och förtryck ytterligare kan vara utsatta om de även tillhör en särskilt sårbar grupp. Samtliga aspekter behöver därmed tas i beaktning vid implementeringar eller åtgärder för att kunna möta den problematik som maktordningarnas samspel kan medföra för yrkesverksammas arbete med denna typ av problematik.

Han trascurrido dieciocho meses desde que se declaró como pandemia la infección COVID-19 ocasionada por el SARS-CoV-2. No existe aún tratamiento contra el virus, salvo el sintomático y recuperativo. El rápido reconocimiento del nuevo coronavirus permitió la elaboración de vacunas que están siendo usadas de emergencia y han permitido disminuir los casos graves, hospitalizaciones, uso de unidades de cuidados intensivos, ventilación mecánica y muertes. Pero aún quedan incógnitas sobre las modificaciones genéticas y variantes que el virus utiliza para una mejor invasión y adaptación a las defensas del ser humano, así como sobre sus consecuencias inmediatas y a largo plazo en el hombre, la mujer y su niño. Parece distante alcanzar la inmunización de rebaño, porque desconocemos la inmunidad proporcionada por la infección y por las vacunas, así como su duración, y por la importante parte de la población que no desea vacunarse. Además, existe insuficiente capacidad de oferta de vacunas, accesibilidad limitada a los servicios de salud, situación económica desfavorable, incremento de la pobreza y sus consecuencias, disminución temporal de la expectativa de vida y otras complicaciones secundarias a la infección por el virus. La presente revisión es un recuento breve de lo avanzado recientemente en el conocimiento y manejo del COVID-19, en momentos en que el Perú celebra el Bicentenario de la Independencia del país del dominio español, un 28 de julio de 1821, y que encuentra a los peruanos en medio de una pandemia agresiva, elusiva y mortal, y con aspectos humanos, poblacionales, económicos y políticos a resolver.

The COVID-19 pandemic caused by SARS-CoV-2 infection poses a serious threat to public health. An explicit investigation of COVID-19 immune responses, particularly the host immunity in recovered subjects, will lay a foundation for the rational design of therapeutics and/or vaccines against future coronaviral outbreaks. Here, we examined virus-specific T cell responses and identified T cell epitopes using peptides spanning SARS-CoV-2 structural proteins. These peptides were used to stimulate peripheral blood mononuclear cells (PBMCs) derived from COVID-19-recovered subjects, followed by an analysis of IFN-γ-secreting T cells by enzyme-linked immunosorbent spot (ELISpot). We also evaluated virus-specific CD4 or CD8 T cell activation by flow cytometry assay. By screening 52 matrix pools (comprised of 315 peptides) of the spike (S) glycoprotein and 21 matrix pools (comprised of 102 peptides) spanning the nucleocapsid (N) protein, we identified 28 peptides from S protein and 5 peptides from N protein as immunodominant epitopes. The immunogenicity of these epitopes was confirmed by a second ELISpot using single peptide stimulation in memory T cells, and they were mapped by HLA restrictions. Notably, SARS-CoV-2 specific T cell responses positively correlated with B cell IgG and neutralizing antibody responses to the receptor-binding domain (RBD) of the S protein. Our results demonstrate that defined levels of SARS-CoV-2 specific T cell responses are generated in some, but not all, COVID-19-recovered subjects, fostering hope for the protection of a proportion of COVID-19-exposed individuals against reinfection. These results also suggest that these virus-specific T cell responses may induce protective immunity in unexposed individuals upon vaccination, using vaccines generated based on the immune epitopes identified in this study. However, SARS-CoV-2 S and N peptides are not potently immunogenic, and none of the single peptides could universally induce robust T cell responses, suggesting the necessity of using a multi-epitope strategy for COVID-19 vaccine design.