Background: In the second year of the COVID-19 pandemic, highly effective and safe vaccines became available. Since patients with rheumatic diseases show increased susceptibility to infections and typical medications raise the risk of severe COVID-19, high vaccination coverage is of significant importance to these patients. Methods: Consecutive patients with different rheumatic diseases were asked for their vaccination status regarding COVID-19, influenza and Streptococcus pneumoniae during their routine consultations. Any reported vaccination was validated with their personal vaccination card and/or by reviewing the CovPass smartphone app. Reasons for not having a COVID-19 vaccination were documented. Results: A total of 201 patients (mean age 62.3 ± 14.1 years) were included, the majority of them (44.3%) with rheumatoid arthritis, followed by spondyloarthritis (27.4%) and connective tissue diseases (21.4%). Vaccination coverage for SARS-CoV-2 was 80.1%; 85.6% got at least the first vaccination shot. Both valid influenza and pneumococcus coverage were associated with a higher probability of SARS-CoV-2 vaccination (odds ratio (OR) 6.243, 95% confidence interval (CI) 2.637–14.783, p < 0.0001 and OR 6.372, 95% CI 2.105–19.282, p = 0.0003, respectively). The main reason for a missing SARS-CoV-2 vaccination (70%) was being sceptical about the vaccine itself (i.e., the subjective impression that the vaccine was not properly tested and fear of unwanted side effects). Conclusions: Vaccination coverage against SARS-CoV-2 is high in patients with rheumatic diseases. Nevertheless, there are unmet needs regarding vaccination education to further increase vaccination rates.

At the beginning of 2020, the SARS-CoV-2 virus, known more commonly as COVID-19, created a pandemic. To slow its spread, healthcare workers were heavily encouraged to vaccinate themselves. However, nurses have been less likely to be vaccinated against COVID-19 than physicians. Four common themes have been associated with vaccine hesitancy among nurses, namely certain demographic variables (e.g., younger age and female sex), fears of the vaccine, conspiracy theories and news sources, and medical and psychological histories that pertain to receiving the COVID-19 vaccine. Thus, this study aimed to identify whether these factors apply to Florida nurses' decisions to get vaccinated after the height of the pandemic. To approach this problem, sixty-five participants were surveyed through a Qualtrics cross-sectional questionnaire. The results revealed that approximately 18.5% of participants were not vaccinated. Trends in the data revealed that older age and a postgraduate education level were associated with receiving the vaccine. Non-vaccinated participants had less confidence in the vaccine's ability to reduce the risk of hospitalization, death, and infection, and they had a stronger fear of side effects and the vaccine's rapid development. Several vaccinated and non-vaccinated participants also believed vaccine conspiracy theories, such as that vaccine safety data is falsified. Many non-vaccinated nurses also received SARS-CoV-2 information from social media or their patients, whereas many vaccinated nurses received information from government news sources or physicians. Non-vaccinated nurses also tended to have more discomfort towards hypodermic injections than vaccinated nurses. These conclusions are generalizable to the nurses of this study and may not be generalizable to all nurses. However, because nurses are on the frontlines of the healthcare field and have an essential role in informing the public about health, the results of this study can help inform vaccine education interventions should a future pandemic occur.

Bakgrund: Under slutet av 2019 bröt en ny epidemi ut med ett nytt coronavirus som orsakar feber och luftvägsbesvär. Under våren 2020 benämndes epidemin som en pandemi. Resurser har fördelats för att kunna ta hand om det stora antalet människor som insjuknat i covid-19.  Anestesisjuksköterskor har under pandemin omplacerats för att vårda intensivvårdspatienter med covid- 19. Intensivvård och anestesisjukvård är två olika men nära besläktade utbildningar. Syfte: Syftet med denna undersökning var att beskriva anestesisjuksköterskors upplevelse av att vårda intensivvårdspatienter med covid-19. Metod: En kvalitativ design med deskriptiv ansats. Åtta anestesisjuksköterskor som uppfyllde urvalskriterierna har intervjuats. Data har analyserats med kvalitativ innehållsanalys. Resultat: Anestesisjuksköterskorna upplevde det som att bli inkastad i något okänt med bristande introduktion. Stora delar av omvårdnaden lämnades över till undersköterskor erfarna inom intensivvård som hjälpte till att leda omvårdnadsarbetet runt patienten. Ett gott samarbete bland kollegor var viktigt för att känna trygghet. Anestesisjuksköterskorna upplevde stress och oro över att arbeta med en ny patientgrupp, medicinteknik och läkemedelshantering.  Anestesisjuksköterskorna kände stolthet över att kunna hjälpa till i en pandemi och göra sitt bästa. De nämnde det som positivt att de hade utvecklats i sin yrkesroll. Diskussion: Arbetets fynd talar om en påfrestande arbetssituation präglad av mycket stress och oro på grund av avsaknad av intensivvårdsspecifik kompetens. Tidigare forskning beskriver att kompetens är ett fenomen som påverkas av utbildning, arbetslivserfarenhet och kvalificering för det speciella yrkesutövan. Slutsats: Patientsäkerheten och omvårdnad av patienten kan brista när personalen saknar kompetens och tid för att utöva sitt arbete. Politiker och chefer behöver mobilisera en sjukvård som klarar av en ny pandemi för att kunna upprätthålla god patientvård- och säkerhet.  Nyckelord: Anestesisjuksköterska, omvårdnad, covid- 19/SARS- CoV-2, pandemi, patientsäkerhet. Keywords: Nurse anaesthetists, nursing, covid-19/SARS-CoV-2, pandemic, patient safety

The current Coronavirus disease 2019 (COVID-19) outbreak, caused by a virus called severe acute respiratory syndrome 2 (SARS-CoV-2), has become a global health emergency. Recent findings in case studies assert that the transmigration of SARS-CoV-2 to the nervous system implicates severe neurotropic pathologies, including the onset of the rare autoimmune disease called Guillain-Barré syndrome (GBS). GBS is recognized as several disorders characterized by immune-mediated polyradiculoneuropathy, which is typically preceded by an infection or other immune stimulation. The symptoms of GBS initially present as acute symmetrical ascending paresthesia, weakness, and paralysis. This meta-analysis serves to help understand the predisposing factors (such as gender, age, comorbidities) and the clinical features of COVID-19- induced GBS. Most patients affected were 40 years or older and comprised 78.2% of all the cases. Males comprised most of the cases (62.8%; n=76). The patient mortality was 9.1%, intensive care unit (ICU) admission was 46.6%, and the need for mechanical ventilation was 35.8%. It was found that concomitant GBS and COVID-19 patients most often presented with increased cerebral spinal fluid (CSF) protein levels (88%; n=106), hyporeflexia or areflexia (87.6%) (n=106), lower limb strength and sensation impairment (91.7%; n=111), upper limb strength and sensation impairment (83.5; n=101), and somatic sensation impairment (73.6%; n=89). It is postulated that COVID-19 triggers the onset of GBS through a “cytokine release storm” (CRS) that occurs in the early stages of the disease. The same cytokines and chemokines involved in this CRS caused by COVID-19 contribute to the onset of GBS. Predisposing factors which influence this concomitance include male gender and older age. Most of the reported symptoms included abnormal limb functions (including paresthesia, weakness, and paralysis) and absent or weak deep tendon reflexes. The most common variant of GBS observed was AIDP, and the most significant laboratory finding among patients was high CSF protein levels.

The COVID-19 pandemic, caused by Severe Acute Respiratory Syndrome Coronavirus 2, or SARS-CoV-2, has been ongoing for over two years. The virus spreads easily and is more unpredictable than well-known viruses like the flu, making it important to have reliable combative measures before we fully drop non-vaccine preventive actions, like mask-wearing.Therefore, we used computational protein modeling to investigate the interactions of three nonstructural proteins (abbreviated Nsp) encoded in the viral RNA genome– Nsp3, Nsp5, and Nsp6 – which are involved in the viral life cycle, with human P-type polyamine transporting ATPases ATP13A2 and ATP13A3, whose disease symptoms when mutated mimic certain COVID-19 complications. Understanding these interactions can help shed light on the mechanism of unexpected symptoms seen in COVID-19 and provide an avenue through which to treat infections. Additionally, papain-like protease (PLpro) and 3-chymotrypsin-like protease (3CLpro), which correspond to Nsp3 and Nsp5, respectively, are highly conserved between SARS-CoV and SARS-CoV-2 and thus make good potential drug targets due to their active sites and presumable lower ability to tolerate mutations (reducing the likelihood of treatments becoming ineffective), although the potential effects on the human proteasome would need to be further investigated. In addition, Nsp6 may help the virus evade host defenses by limiting the ability of autophagosomes to deliver viral particles to lysosomes, so limiting its interactions may increase the ability of the host cell to target its viral invader. One compound in particular, Haloperidol, showed promising results; predicted docking (via computational molecular docking software) to Nsp6 alone, as well as to Nsp6-heteroprotein complexes suggested strong binding, indicating a potential strong interaction that could impact the viral protein function and thus the viral life cycle.

The purpose of this study was to focus on whether solely obesity (measured by BMI) leads to an increased risk of COVID-19 mortality in terms of excess in-hospital deaths. As the grim milestone of one million deaths in the United States from COVID-19 was reached, one could assume the disease would continue to coexist with humanity in the long term. While vaccination continued to limit the spread of COVID-19, it was essential to investigate risk factors that may exacerbate the severity of the illness in humans. Obesity is already a global pandemic affecting 40% of Americans and over 650 million people worldwide. Obesity is connected to an entire range of clinical conditions including some of the leading causes of death worldwide making it a more generalizable statistic. Furthermore, the purpose of this study was to conduct a systemic review of major risk factors between obesity and COVID-19, and this analysis shall ascertain which factors have the most predictive value in determining mortality and severity of the condition. Ten research studies of 3,780,926 COVID-19 patient cases were included. Meta-analysis results indicate a pooled OR of 0.93 (0.71-1.23, p = 0.627) for in-hospital mortality of obese patients relative to non-obese patients when adjusted for confounders. All comorbidities associated with the development of severe disease were found to have an equal chance of leading to mortality. In other words, obesity did not lead to a statistically significant risk of dying from COVID-19.

I december 2019 i Wuhan, Kina, blev en grupp personer infekterade av det nya viruset SARS-CoV-2 som inducerade sjukdomen COVID-19. Sjukdomen påverkar lungfunktionen och studier har visat att långvarig påverkan på lungfunktionen kan förekomma. Syftet med den aktuella studien var att undersöka långvariga effekter av COVID-19 på diffusionskapaciteten i lungorna. Studier som undersökte diffusionskapaciteten, mätt med kolmonoxid (DLCO), hos patienter minst 30 dagar efter insjuknande i COVID-19 samlades in och analyserades. Resultatet visade att en stor del av deltagarna hade DLCO &lt;80% av det förväntade värdet. Det visade även att diffusionskapaciteten kan vara nedsatt upp till sex månader efter utskrivning från sjukhus. Då COVID-19 är en ny sjukdom var den aktuella studien begränsad av antalet studier inom området. Framtida studier bör undersöka effekterna av COVID-19 på lungfunktionen under ett längre tidsspann. Slutsatsen i den här litteraturstudien var att COVID-19 påverkar diffusionskapaciteten i lungorna. Långvariga nedsättningar i diffusionskapaciteten har, än så länge, kunnat påvisas upp till sex månader efter sjukdom. Allvarligt insjuknande i COVID-19 ökar risken för långvariga DLCO -nedsättningar.

As obligatory intracellular parasites, viruses are in a constant battle with their host to establish infection. They can facilitate their propagation by modulating host immune or metabolic pathways. This modulation involves targeting various molecular factors such as microRNAs (miRNA), enzymes, or small molecules. Understanding how viruses alter the chemical makeup of a cell is crucial to identifying what pathways are being targeted, furthering our understanding of the virus life cycle, and may aid in identifying biomarkers of disease. Here, we examine host-virus interactions in the context of two viruses, hepatitis c virus (HCV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). First, the modulation of serine hydrolases by a pro-viral microRNA, miRNA-122, is investigated using activity-based protein profiling (ABPP). This study identifies a downstream target of miRNA-122 that is differentially activated during HCV infection which can be targeted pharmacologically to reduce HCV infectivity. Second, we apply similar techniques to identify serine hydrolase changes associated with SARS-CoV-2 infection. Results point towards enrichment of endocannabinoid metabolism which may offer an alternative therapeutic avenue for combating SARS-CoV-2 infection. Together, the work presented in this thesis provides avenues for further investigation into miRNA-122 interactions during HCV infection and endocannabinoid metabolism in SARS-CoV-2 infection.

Unexpected high mutations detected in new emerging variants of concern (VOCs) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), especially in the case of omicron, raises concerns and efforts to understand their evolutionary trajectory. Several hypotheses have been discussed in literature to conceptualize the source of their emergence, including intra-host viral evolution in immunocompromised patients. These patients grant opportunities for the emergence of new variants through a persisting virus winning against host immunity, and selection for viral mutations driven by treatment interventions. VOCs have in common high mutation rate exceeding the average rate of 1-2 mutations per month. Not many studies have investigated the evolutionary rate of SARS-CoV-2 in immunocompromised candidates. Therefore, the purpose of this study is to reveal potential mechanisms underlying the emergence of VOCs by exploring substitution rate of SARS-CoV-2 genomes from surveyed COVID-19 immunocompromised patient’s studies. First, SARS-CoV-2 genome sequences were collected at sequential time series throughout host infection, which were reported in the previous studies. Filtration criteria was applied to reanalyze patients with prolonged infection documented for ≥ 2 months, and comprehensive sequenced samples for ≥ 6 time points. Then, phylogenetic analysis was conducted using Nextclade (https://clades.nextstrain.org/), followed by mutation rate analysis using two substantial similar approaches to calculate the rate in i) substitutions per month and ii) substitutions per site (per year). The mutation tendency of SARS-CoV-2 in immunocompromised hosts was compared to reported VOCs, particularly to omicron. The highest observed mutation rate accounted for approximately 2.2 mutations per month, which is higher than the average rate. High mutation rate was due to prolonged infection and selection pressure by treatment interventions (i.e., convalescent plasma and antibodies). Here, higher rate of intra-host viral evolution in immunocompromised patients is detected, potentially leading to the emergence of VOC. Hence, this research highlights the need for sequencing efforts in high-risk individuals, updating treatment strategies along with further analysis on adaptive mutants pronounced due to intra-host evolution. Together, such findings provide an ultimate synergy for future public health guidelines and infection control measures.

<p>  </p> <p>Seven-membered ring structures are one of the most important structural motifs found widely in natural products and bioactive molecules. Although several [5+2]-cycloaddition reactions have been developed to construct these seven membered cores, asymmetric cycloaddition reactions are less explored. Described in Chapter-1 is a base mediated intramolecular diastereoselective [5+2]-cycloaddition reaction that afforded highly functionalized seven membered rings in good yields and excellent diastereoselectivities. The high diastereoselectivity is controlled by the alkyl stereocenter and the chain length of the alkene tether. The existing chirality of the substrate can direct the stereochemical outcome of the [5+2]-cycloaddition reaction. Furthermore, this methodology has been applied to synthesize various potent HIV-1 protease inhibitors. </p> <p>COVID-19 pandemic has profoundly affected life around the globe and costed us 6 million lives. Therefore, there is an urgent need for rational design of new drug candidates to specifically target different SARS-CoV-2 proteins. Recently, Pfizer developed an FDA-approved antiviral therapeutic agent, Paxlovid, targeting SARS-CoV-2 3CLpro. Chapter-2 discusses a concise synthetic route to synthesize active component of Paxlovid, Nirmatrelvir, in 6-steps without any epimerization. We have also developed a series of potent covalent inhibitors targeting SARS-CoV-2 3CLprotease and compared the antiviral activities of these inhibitors with that of Nirmatrelvir. </p> <p>In the final chapter, a concise partial synthesis of the segment A of (-)-Rafonin is discussed. (-)-Rasfonin is an antitumor agent that induces apoptosis in <em>ras</em>-dependent cells. We have proposed an asymmetric chiron approach to install the α-pyranone ring of rasfonin. Our goal is to perform SAR studies on this natural product by designing various analogues. </p>