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Development of a simplified and cost effective norovirus capsid typing method using next generation sequencingEriksson, Ronnie January 2023 (has links)
Human noroviruses are a major cause of acute gastroenteritis worldwide and can betransmitted through consumption of contaminated raw food. Shellfish like oysters can becontaminated by human sewage during production and accumulate multiple Norovirus strainsin low concentrations. Here we developed a simplified and cost effective targetedmetagenomic approach by sequencing PCR amplicons with next generation sequencing(NGS) of the capsid (VP1) viral gene. New design of reverse primers using the codehopstrategy and direct addition of illumina adapter with one step RT-PCR and sequencing onnano chip reduced hand on time and cost of the analysis. A mix of faecal samples and oystersamples associated with outbreaks were used to evaluate the ability and limitations in theidentification of strains from Norovirus genogroup I (GI) and genogroup II (GII). Withsamples containing only one genotype the method was able to identify all strains. Usingartificially mixed samples the method was able to identify almost all strains except a few GIIat low concentrations. Oyster samples showed more limitations for the method and it waswere only able to identify the strain in some of the samples but did find multiple GI strains inmore than one sample. Despite some limitations, the simplified method for VP1-targetedmetagenomics is a sensitive approach allowing the study of norovirus diversity incontaminated oysters and the identification of norovirus strains implicated in outbreaks. Thisat a lower cost and hands on time compared to published methods.
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The Effect of Socioeconomic, Patient, and Logistic Determinants on Antiretroviral Pre-Treatment Drug Resistance A Regression Analysis ModelFaza, Linah January 2022 (has links)
Introduction Human immunodeficiency virus (HIV) is a double stranded RNA retrovirus. According to the World Health Organization more than 30 million individuals were estimated to have HIV by the end of 2020, about 60% of which are in the African region. Pre-treatment drug resistance (PDR) can be defined as the resistant virus strains transmitted at the time of infection or acquired during previous exposure to ARV. This study asses the effect of drivers in PDR. Method: This study was conducted with data extracted from published, publicly available data bases and reports by international organizations. The main sources were United Nation data bases and published reports from World Health Organization. Inferential statistics were used to assess the PDR to anti-retroviral drugs. A linear regression model was used to investigate the association between PDR and previous exposure to anti-retrovirals and anti-retroviral therapy, pre-exposure prophylaxis, national health expenditure, human development index, and drug stock-out for different classes of anti-retroviral drugs. Results: The result indicated that NNRTI drug resistance was most common, and seven out of 29 countries had PDR to all four drug classes. The human development index was positively associated with INSTI and PI PDR (p<0.05), while NNRTI and NRTI were mainly positively associated with previous exposure to anti-retrovirals. Conclusion: This study assessed the impact of socio-economics determinants (human development index and national health expenditure), drug logistic determinants (stock-out), and patients’ determinants (adherence and previous exposure to any kind of anti-retrovirals) on PDR. For expensive drug classes (PI and INSTI) the resistance was positively associated with human development index. Previous exposure to anti-retrovirals was associated with increased resistance in NNRTI and NRTI.
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Åtgärder som främjar sjuksköterskansidentifiering av sepsis : En litteraturöversikt med kvantitativ ansats / Interventions that promote the nurse's identification of sepsis : A literature review with a quantitative approachBerlin, Josefine, Svensson, Lisa January 2023 (has links)
Bakgrund: Sepsis är ett akut sjukdomstillstånd med en hög mortalitet världen över.Tidig identifiering och snabb behandling är viktig för patientens överlevnad.Sjuksköterskan har i sitt patientnära arbete en unik position att snabbt identifierasepsis och initiera behandling. För att möjliggöra en säker vård för patient, kollegoroch vårdansvarig sjuksköterska ska sjuksköterskan arbeta förebyggande ochpatientsäkert. Syfte: Att kartlägga åtgärder som främjar sjuksköterskans förmåga attidentifiera sepsis på sjukhus. Metod: En litteraturöversikt har genomförts för attskapa en överblick av det aktuella kunskapsläget. För att besvara syftet användesartiklar med en kvantitativ metod. Med hjälp av Polit och Becks niostegsmodellanalyserades artiklar som sedan presenterades i resultatet. Resultat: Resultatetvisade att sjuksköterskorna använde sig utav utbildning, riktlinjer samtscreeningverktyg för att främja identifieringen utav sepsis. Signifikanta skillnader sågsi relation till de olika åtgärderna. Skillnaderna visade bland annat en minskadmortalitet och minskad vårdtid. Slutsats: Sjuksköterskan har en central roll i attidentifiera sepsis. Resultatet förväntas identifiera åtgärder som i den kliniskavardagen kan hjälpa framtida sjuksköterskor eller annan vårdpersonal. Genom attsjuksköterskan är ödmjuk för den egna kompetensen, tar hjälp av screeningverktygoch vidhåller de riktlinjer som finns kan en grund för säker vård byggas. / Background: Sepsis is an acute illness with a high mortality rate worldwide. It istherefore important to act quickly as rapid identification and treatment can be crucialfor the patient's survival. The nurse has, with her close work with the patient a uniqueposition to quickly identify sepsis and initiate treatment. In order to enable safe carefor both the patient, colleagues and healthcare providing nurse, the nurse must workpreventively and in a patient safe manner. Aim: To map interventions that promotethe nurse's identification of sepsis in a hospital setting. Method: A literature reviewhas been carried out to create an overview of the current state of knowledge. To answerthe purpose, articles with a quantitative methodology were chosen. Using Polit andBeck's nine-step model articles were analyzed and then presented in the results.Results: The results showed that the nurses used training, protocols and screeningtools to promote the identification of sepsis. Significant differences were seen inrelation to the various interventions. The differences showed for instance a decreasedmortality and abbreviated the hospital stay. Conclusion: The nurse has a central rolein identifying sepsis. The results are expected to identify measures that can help futurenurses or other healthcare professionals in the clinic. By the nurse being humble abouther own competence, using screening tools and maintaining the existing protocols, afoundation for safe care can be built.
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Faktorer som påverkar sjuksköterskans identifiering av sepsis : En kvantitativ litteraturöversikt / Factors influencing the nurse´s identification of sepsis : A quantitative literature reviewKalbe, Clara, Ragnarsson, Mathilda January 2024 (has links)
Bakgrund: Sepsis är en livshotande överreaktion i immunförsvaret som kan uppstå av en infektion. Tidig identifiering av sepsis är fundamentalt för att tillhandahålla snabb och effektiv vård. Detta skapar goda förutsättningar för patientens överlevnad. Syfte: Att kartlägga faktorer som påverkar sjuksköterskans identifiering av sepsis. Metod: För att sammanfatta och skapa en bild av det nuvarande kunskapsläget har en litteraturöversikt med kvantitativ design genomförts. Polit och Becks 9-stegs flödesschema utgjorde strukturen för skapandet av litteraturöversikten. Sökningar i databaserna CINAHL, MEDLINE och PsycINFO resulterade i 14 artiklar till resultatet, publicerade mellan 2012–2023. Resultat: I resultatet framkom att faktorer som påverkar sjuksköterskans identifiering av sepsis var sjuksköterskans kunskap, genomgången utbildning, hjälpmedel vid sepsisidentifiering samt bristande arbetsförhållanden. Bland annat framkom att sepsisidentifiering försenades på grund av bristande kunskap om sepsissymtom samt hög arbetsbelastning, och främjades av utbildning om sepsis och användning av screeningverktyg. Slutsats: Litteraturöversikten kartlägger faktorer som främjar och hindrar sjuksköterskans identifiering av sepsis. Detta möjliggör tidig adekvat behandling som skapar goda förutsättningar för överlevnad. Kärnkompetensen samverkan i team är grundläggande för samordning av vårdens resurser för en god och säker vård. / Background: Sepsis is a life-threatening overreaction in the immune system that can arise from an infection. Early identification of sepsis is fundamental to provide prompt and effective care. This creates good prerequisites for the patient's survival. Purpose: To map factors that influence the nurse's identification of sepsis. Method: To summarize and create a picture of the current state of knowledge a literature review with a quantitative design was conducted. Polit and Beck's 9-step flow chart formed the structure for the creation of the literature review. Searches in the databases CINAHL, MEDLINE and PsycINFO resulted in 14 articles used in the result, published between 2012-2023. Results: The result showed that factors influencing the nurse's identification of sepsis were the nurse's knowledge, completed training, aids for sepsis identification and lacking working conditions. Among other things, it appeared that sepsis identification was delayed due to a lack of knowledge about sepsis symptoms and high workload and was improved by education about sepsis and the use of screening tools. Conclusion: This literature review identifies factors that promote and impede the nurse’s identification of sepsis. This enables early adequate treatment which creates good conditions for survival. The core competency of collaboration in teams is fundamental for coordinating care resources for good and safe care.
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Genetic subtypes in unicellular intestinal parasites with special focus on BlastocystisForsell, Joakim January 2017 (has links)
The development of molecular tools for detection and typing of unicellular intestinal parasites has revealed genetic diversities in species that were previously considered as distinct entities. Of great importance is the genetic distinction found between the pathogenic Entamoeba histolytica and the non-pathogenic Entamoeba dispar, two morphologically indistinguishable species. Blastocystis sp. is a ubiquitous intestinal parasite with unsettled pathogenicity. Molecular studies of Blastocystis sp. have identified 17 genetic subtypes, named ST1-17. Genetically, these subtypes could be considered as different species, but it is largely unknown what phenotypic or pathogenic differences exist between them. This thesis explores molecular methods for detection and genetic subtyping of unicellular intestinal parasites, with special focus on Blastocystis. We found that PCR-based methods were highly sensitive for detection of unicellular intestinal parasites, but could be partially or completely inhibited by substances present in faeces. A sample transport medium containing guanidinium thiocyanate was shown to limit the occurrence of PCR inhibition. The prevalence of Blastocystis in Swedish university students was over 40%, which is markedly higher than what was previously estimated. Blastocystis ST3 and ST4 were the two most commonly found Blastocystis subtypes in Sweden, which is similar to results from other European countries. Blastocystis sp. and Giardia intestinalis were both commonly detected in Zanzibar, Tanzania, each with a prevalence exceeding 50%. Blastocystis ST1, ST2, and ST3 were common, but ST4 was absent. While G. intestinalis was most common in the ages 2-5 years, the prevalence of Blastocystis increased with increasing age, at least up to young adulthood. We found no statistical association between diarrhoea and Blastocystis sp., specific Blastocystis subtype or G. intestinalis. Metagenomic sequencing of faecal samples from Swedes revealed that Blastocystis was associated with high intestinal bacterial genus richness, possibly signifying gastrointestinal health. Blastocystis was also positively associated with the bacterial genera Sporolactobacillus and Candidatus Carsonella, and negatively associated with the genus Bacteroides. Blastocystis ST4 was shown to have limited intra-subtype genetic diversity and limited geographic spread. ST4 was also found to be the major driver behind the positive association between Blastocystis and bacterial genus richness and the negative association with Bacteroides.
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Effekten och potentiella risker med bedaquiline, delamanid och pretomanid vid behandling av multiresistent tuberkulos / The efficiency and potential risks with bedaquiline, delamanide and pretomanide in the treatment of multidrug-resistant tuberculosisJansson, Alexandra January 2019 (has links)
Introduktion: tuberkulos går tillbaka ända till stenåldern och det var inte förrän på 1800-talet som Robert Koch upptäckte att det var Mycobacterium tuberculosis (M. tuberculosis) som orsakade tuberkulos. Idag drabbas cirka 10 miljoner årligen av tuberkulos och år 2017 uppstod cirka 600 000 nya fall av multiresistent tuberkulos (MDR-TB). M. tuberculosis är en bakterie med en unik cellvägg bestående av en hög koncentration av mykolsyra. Bakteriens fettrika cellvägg kan i sin tur fungera som en barriär mot läkemedel som behandlar tuberkulos, vilket gör sjukdomen svårbehandlad. Tuberkulos smittar via små luftburna droppar men det är bara cirka 10 % av alla som smittas som drabbas av sjukdomssymtom. Tuberkulos diagnosticeras vanligen med hjälp av sputumprover från de djupa luftvägarna och för att finna resistens för läkemedel görs bakterieodlingar i flytande eller fast medium. Tuberkulos behandlas med en kombination av flera olika läkemedel. Standardbehandlingen (HRZE) som används vid behandling av tuberkulos består av isoniazid, rifampicin, pyrazinamid och etambutol. Vid en felaktig eller ofullständig behandling med dessa läkemedel kan bakterien utveckla resistens och MDR-TB kan uppstå. Vid MDR-TB är patienten vanligtvis resistent mot isoniazid och rifampicin vilket gör sjukdomen svår att behandla och en annan kombination av läkemedel behövs. Bedaquiline, delamanid och pretomanid är nyutvecklade läkemedel som förhoppningsvis ska kunna användas hos patienter med MDR-TB. Syfte: syftet med arbetet var att undersöka effekten och potentiella risker med bedaquiline, delamanid och pretomanid vid behandling av MDR-TB. Metod: artiklar till litteraturstudien erhölls från databaserna PubMed och ClinicalTrials där totalt 7 artiklar valdes ut för att granska effekten samt risken med bedaquiline, delamanid och pretomanid hos patienter med MDR-TB. Resultat: det erhållna resultatet från artiklarna erhölls genom att framförallt analysera den primära utkomsten. Alla artiklar tyder på att bedaquiline, delamanid samt pretomanid har en god effektiv baktericid effekt på M. tuberculosis och kan möjligtvis förkorta behandlingsperioden. Men alla läkemedel gav även ett flertal biverkningar så som, huvudvärk, illamående, yrsel, hyperurikemi och ett förlängt QT-intervall. Men biverkningarna klassades som milda till moderata. Diskussion: många biverkningar uppstod i studierna och endast ett fåtal deltagare deltog. Däremot observerads det att dessa nya kombinationer kan även minska utvecklingen av ytterligare resistens för läkemedel. Trots vissa avvikelser i studierna kan delamanid, bedaquiline och pretomanid vara nya alternativa behandlingar för MDR-TB. Men fler studier med en större studiepopulation behöver utföras för att säkerställa säkerheten samt effektiviteten av samtliga läkemedel. Men samtliga läkemedel visar lovande resultat i nuvarande studier för den framtida kampen mot MDR-TB. / Archeological findings of tuberculosis can be found way back to the Stone Age but it wasn’t before the 18th century that Robert Koch discovered that it was Mycobacterium tuberculosis (M. tuberculosis) who caused the disease tuberculosis. Current data indicates that approximately 10 million people are infected with tuberculosis each year and 600 000 new cases of multidrug resistance tuberculosis (MDR-TB) was observed in 2017. Tuberculosis is a bacterium with a unique cell wall consisting of a high concentration of mycolic acid. The fatty cell wall of the bacteria can act as a barrier against antituberculotic drugs, making the disease difficult to treat. Tuberculosis is a disease who can be spread among people via airborne droplets but only about 10 % of all people who are infected are affected by disease symptoms. Tuberculosis is usually diagnosed by spot-sputum samples from deep within the airways. Resistance to antituberculotic drugs are detected by culture growth of the bacteria on either a liquid or solid medium. Tuberculosis is treated with a combination of several different drugs such as isoniazide, rifampicine, pyrazinamide and ethambutol. Also called HRZE and is a standard regimen for tuberculosis. If treatment occurs incorrectly or is incomplete the bacteria can develop resistance to these drugs and MDR-TB can emerge. Patients with MDR-TB is usually resistant to either or both isoniazide and rifampicine which makes the disease difficult to treat and another combination of drugs is needed. Bedaquiline, delamanide and pretomanide are newly developed drugs that can hopefully be used in the treatment of MDR-TB. The purpose of the thesis was to analyze the efficacy and potential risks with bedaquiline, delamanide and pretomanide in the treatment of MDR-TB. The articles for this literature study were obtained from the two databases PubMed and ClinicalTrials. A total of 7 articles were chosen to analyze the efficacy and potential risks with bedaquiline, delamanide and pretomanid used in treatment in patients with MDR-TB. The result obtained from the articles was obtained by primarily analyzing the primary outcome from each article. All articles suggest that bedaquiline, delamanide and pretomanide have a favorable bactericidal efficacy against M. tuberculosis and may shorten the treatment period. However, all of the studied drugs produced numerous side effects such as headaches, nausea, dizziness, hyperuricemia and an extended QT interval. Although all the side effects that occurred in the studies were classified as mild to moderate. Many side effects occurred in the studies and only a few participants participated in each study. However, it was observed that the new combinations with bedaquiline, delamanide and pretomanide can reduce the development of additional drug resistance. Despite some deviations in the studies, bedaquiline, delamanide and pretomanid may be new alternative treatments for MDR-TB. But more studies with a larger study population is needed to ensure the safety profile and efficacy of all of the drugs above. However, bedaquiline, delamanide and pretomanid show promising results in current studies for the future fight against MDR-TB.
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The Effect of Water, Sewage and Hand Hygiene on Waterborne Diseases in Saudi ArabiaAlshareef, Hanouf January 2021 (has links)
Waterborne diseases are illnesses caused by microscopic organisms, like viruses, bacteria and parasites, that transmitted via the fecal-oral route through ingestion of contaminated water or food or by direct person to person contact. The transmission cycle can be broken through safe water supplies, maintaining standards of sanitation and proper handwashing practices. Two waterborne diseases are considered in this study: hepatitis A and amebic dysentery. The study aimed to understand the important factors for preventing waterborne diseases in order to improve public health. A descriptive cross-sectional study was conducted to assess the effect of different drinking water sources, sewage systems and different active practices of soap use for hand washing on incidence of waterborne diseases in different regions in Saudi Arabia. Data was obtained from Ministry of Health and Household Environment Survey provided by General Authority for Statistics. Statistical analysis performed by using general linear model and type II Analysis of Variance. In comparison of different drinking water sources, this study showed borderline rise in incidence of waterborne diseases with the use of private well water. Whereas different sewage systems had no clear effect on the incidence of waterborne diseases. The study also revealed that not using soap for hand washing would increase the risk for hepatitis A infection. Moreover, the study showed significant decline in waterborne diseases incidence when access to filtered water combined with regular soap use in the same linear model.
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Kan tranbär förebygga urinvägsinfektioner? : Med primärt fokus på äldre vårdtagare / Can cranberries be used as prevention of urinary tract infections? : With a primary focus on older care recipientsKhadida, Savin, Al-Hedr, Jelan January 2021 (has links)
Bakgrund: Urinvägsinfektion (UVI) är den vanligaste förekommande bakteriella infektionen på äldreboenden. Idag behandlas den oftast med antibiotika men med det ständiga hotet av antibiotikaresistens krävs det andra alternativ till prevention. Tranbär är en nordamerikansk frukt som förekommer i olika former; tranbärsjuice, tranbärskapslar, tranbärspulver eller tranbärscocktails och som används som alternativ behandling. På grund av anatomiska skillnader, där kvinnans urinrör är närmre anus, är kvinnor överrepresenterade i studier om urinvägsinfektion. Syfte: Syftet var att med hjälp av studier undersöka om det går att förebygga urinvägsinfektioner, med fokus på äldre, med hjälp av tranbär och redogöra för andra effekter av dess behandling. Metod: En kvantitativ litteraturstudie med artiklar hämtade från CINAHL och PubMed, internationella databaser för forskning inom medicin och omvårdnad. Artiklarna granskades med SBU:s (statens beredning för medicinsk och social utvärdering) mall för kvalitetsgranskning. Resultat: Resultatet av denna studie visar på att tranbär uppvisar effekt i prevention av urinvägsinfektioner i jämförelse med placebo eller annan intervention. Enstaka studier påvisar ett icke signifikant resultat trots en viss minskning i incidensen av urinvägsinfektioner. Speciellt god effekt har tranbär på Escherichia coli (E. coli bakterier) och dess vidhäftningsförmåga. Tranbär påverkar E. coli bakteriens fimbrier och försvårar därmed vidhäftningen. Till följd av tranbärsintervention rapporteras minskad användning av antibiotika. Konklusion: Tranbärets effekt har uppvisat flera positiva resultat och är ett alternativ som är värt att överväga. Tranbär är ett billigare alternativ som kan ersätta kontinuerliga doser av antibiotika och det medför inte samma mängd biverkningar. Om det dessutom används som tillägg till antibiotikabehandling kan det minska antalet antibiotikaförskrivningar vilket på lång sikt minskar utvecklingen av antibiotikaresistens. Tranbär kan rekommenderas till äldre för att förebygga och behandla urinvägsinfektioner. / Background: Urinary tract infection (UTI) is the most common bacterial infection in nursing homes. Today it is usually treated with antibiotics but with the constant threat of antibiotic resistance other alternatives to prevention are required. Cranberries are a North American fruit that comes in various forms; cranberry juice, cranberry capsules, cranberry powder or cranberry cocktails. Due to anatomical differences, where the woman's urethra is closer to the anus, women are overrepresented in studies of urinary tract infections. Aim: The aim was to examine with the help of studies whether it is possible to prevent urinary tract infections, with focus on older care recipients, with the help of cranberries and account for other effects of its treatment. Method: A quantitative literature review with articles taken from CINAHL and PubMed, international databases for research in medicine and nursing. The articles were reviewed with SBU's (the Swedish Agency for Medical and Social Evaluation) criteria for quality review. Results: The results of this study show that cranberry demonstrates an effect in the prevention of urinary tract infections in comparison to placebo or other interventions. A few of the studies show a non-significant result despite some reduction in the incidence of urinary tract infections. Cranberry has particularly good effect on Escherichia coli (E. coli bacteria) and its adhesion. Cranberries affects the fimbriae of E. coli bacteria to make adhesion more difficult. Less use of antibiotics is reported after intake of cranberry. Conclusion: The effect of cranberry has shown several positive results and is an option worth considering. Cranberries can be seen as an unnecessary cost but could replace continuous doses of antibiotics. Cranberries are also a cheaper alternative and they do not cause the same amount of side effects as antibiotics. If it is used as a supplement to antibiotic treatment, it may not be necessary to prescribe antibiotics, which in long-term reduces the development of antibiotic resistance. Cranberry can be recommended to elderly for prevention and treatment of urinary tract infections.
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Vaccin mot SARS-CoV-2 – en utvärdering av effektivitet och säkerhet av ledande vaccin : En Litteraturstudie / Vaccine against SARS-CoV-2 – an evaluation of effectivity and safety of the leading vaccines : A Literature StudyWrywood, Sean January 2021 (has links)
Introduktion: Coronavirus är RNA-virus med ett lipidhölje som är täckt utav karaktäristiska spikprotein. De mest kända coronavirusvarianterna är SARS-CoV-1 som var aktiv mellan 2002-2004, MERS-CoV som har varit aktiv sedan 2012 och SARS-CoV-2 som har varit aktiv sedan 2019–tillsvidare. SARS-CoV-2 infektionen betecknades januari 30 2020 som en pandemi. Flera läkemedelsföretag har forcerat ??? till att framställa vaccin riktad mot SARS-CoV-2, “The United States Food and Drug Administration” (FDA) och “European Medicines Agency” (EMA) har nödgats att ge ut “Emergency Use Authorization (EUA) i hopp om att få kontroll på dess spridining. Syfte och mål: Syftet med arbetet är att undersöka säkerheten och effektiviteten hos de EMA-godkända vaccinerna riktade mot SARS-CoV-2. Metod: Studierna för vardera vaccin hittades och valdes ut genom World Health Organizations (WHO) “Draft landscape and tracker of COVID-19 candidate vaccines”. Totalt inkluderades åtta studier baserade på tio kliniska prövningar som undersökte säkerheten och effektiviteten hos de fyra ledande vaccinerna från Pfizer BioNTech, Moderna, AstraZeneca och Johnson & Johnson. Resultat: De fyra undersökta vaccinerna visade en god säkerhet utan grövre biverkningar. De vanligaste biverkningarna hos samtliga vaccin var lokal smärta, trötthet och huvudverk. Dessa biverkningar varade mellan en till två dagar efter vaccination och var till större del milda. Större skillnader kunde ses hos de olika vaccinernas effektivitet, Pfizer BioNTech och Modernas mRNA-vacciner visade på effektiviteter runt 95% medan AstraZeneca och Johnson & Johnsons adenovirus-vektor-vacciner visade på effektiviteter runt 66-70%. Diskussion: Inga större skillnader i säkerhet kunde ses mellan de undersökta vaccinerna. AstraZeneca använde ett influensa vaccin istället för isoton vattenlösning till deras kontrollgrupper. Detta kan ha haft en påverkan på placebo och resultaten från deras prövningar. En tydlig skillnad i effektivitet kunde ses mellan de olika vaccintyperna, vilket har ett stort inflytande på hur lätt man kan inducera flockimmunitet hos en befolkning. Eftersom flockimmunitet har en stor roll i både att bromsa spridningen men även i att förebygga förekomsten av nya virus varianter så bör endast mRNA vacciner rekomenderas om möjligt. / Introduction: Coronaviruses are RNA viruses with a lipid envelope that is covered by characteristic spike protein. The most well-known coronaviruses are SARS-CoV-1 which were active between 2002-2004, MERS-CoV which is active since 2012 and SARS-CoV-2 which is active since 2019. SARS-CoV-2 was designated a pandemic January 30, 2020. Several pharmaceutical companies have been rushing to produce vaccines targeting SARS-CoV-2, The United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have had to issue Emergency Use Authorization (EUA) in the hope of gaining control of its spread. Objective: The purpose of this study is to investigate the safety and efficacy of the EMA-approved vaccines targeting SARS-CoV-2. Method: The studies for each vaccine were found and selected through the World Health Organizations' (WHO) "Draft landscape and tracker of COVID-19 candidate vaccines". A total of eight studies were included based on ten clinical trials examining the safety and efficacy of the four leading vaccines from Pfizer BioNTech, Moderna, AstraZeneca and Johnson & Johnson. Results: The four vaccines examined showed good safety without any serious side effects, the most common side effects with all vaccines were local pain, fatigue, and headache. These side effects lasted between one to two days after vaccination and were mostly mild. Larger differences could be seen in the efficacy of the different vaccines, with Pfizer BioNTech and Moderna's mRNA vaccines showing efficacies of around 95%. While AstraZeneca and Johnson & Johnson's adenovirus vector vaccines showed efficacies of around 66-70%. Discussion: No major differences in safety could be seen between the vaccines examined. AstraZeneca used an influenza vaccine instead of isotonic aqueous solution for their control groups, this may have had an impact on placebo and thus the results of their trials. A clear difference in efficacy could be seen between the different types of vaccines. This has a great influence on how easily one could induce herd immunity to a population. Herd immunity plays a major role in both slowing the spread but also in preventing the occurrence of new virus variants, therefore mRNA vaccines should be recommended if possible.
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Studies of broad-spectrum inhibitors against main protease of SARS-CoV-2 and other CoronavirusesStanciu, Alexandra January 2023 (has links)
Coronaviruses have caused three large outbreaks in the past century. The most recent one, also still ongoing, is represented by the SARS-CoV-2/Covid-19 pandemic. Efforts have been taken to develop efficient vaccines and antivirals and one of the major virus-based targets in drug development is represented by the main protease of these viruses. Main proteases are proteins (cysteine hydrolases) with high level of conservation among different coronaviruses and have an important role in the virus life cycle. Due to the need of developing broad-spectrum antivirals against Coronaviruses, this study aimed to set up a CPE-based assay for testing compounds against the main protease of human coronavirus 229E. An optimized TCID50 protocol was established by using MRC-5 cells, at a density of 1x104 cells/ml with a 3h incubation prior infection with a concentration of 10-1 of HCoV-229E. The cell viability was assessed through MTT assay. Using reference compounds, with previously demonstrated antiviral potency against the main protease of different coronaviruses (GC-376, Nirmatrelvir), the efficiency of the conceived assay was validated (GC-376 EC50 = 1.24 μM; Nirmatrelvir Ec50= 0.72 μM). Compound 19 was proved to also be active against the main protease of HCoV-229E (EC50 = 0.22 μM), and together with previous findings, it was concluded that this compound has a broad-spectrum activity. Newly developed compounds MP17 and MP19 were also demonstrated to be efficient against HCoV-229E. As a future perspective, further investigations of these compounds should take place for the identification of EC50 values.
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