Tillväxthormon och insulinliknande tillväxtfaktor-1 är blodprover som tas vid misstanke om akromegali. Immulite 2000 XPi är ett instrument som använder chemiluminescent microparticle immunoassay metodik för att kvantitativt mäta koncentrationen av GH och IGF-1. Analys av biokemiska markörer påverkas av flera olika faktorer. En viktig sådan faktor är hemolys. Hemolys innebär att de röda blodkropparna går sönder, vilket leder till frisättning av dess innehåll såsom hemoglobin i serum/plasma. Syftet med detta projekt var att undersöka hur hemolys påverkar resultatet av GH- och IGF-1-prover på immulite 2000 XPi. Utifrån erhållna resultat kommer klinisk kemi vid Universitetssjukhuset Örebros laboratorie rutiner vid hemolytiska prover på GH eller IGF-1 att uppdateras . Hemolys tillverkades och tillsattes till olika serumprover med låg och hög nivå av GH respektive IGF-1 för att erhålla prover med varierande grad av hemolys. Resultatet visade att ökande hemolysindex korrelerar med GH- respektive IGF-1-koncentrationer, med undantag för den låga GH koncentrationen som inte uppvisade någon korrelation till hemolysindex. En 10%:ig skillnad av GH och IGF-1- koncentrationer uppnåddes vid en ökning av hemolysindex med 555,40 mg/dL för GH respektive 333,3 mg/dL för IGF-1.Utifrån resultaten var hemolysgränsen likvärdig med tillverkarens gränser. Därför kan klinisk kemi på Universitetssjukhuset Örebro fortsätta med nuvarande hemolysgränser. / Growth hormone and insulin-like growth factor-1 are blood samples taken upon suspicion of acromegaly and for follow-up of acromegaly treatment. Immulite 2000 XPi is an instrument that uses chemiluminescent microparticle immunoassay method to quantitatively measure the concentration of GH and IGF-1. Analysis of biochemical markers is affected by several different factors. An important such factor is hemolysis. Hemolysis means that the red blood cells break, whose contents leak into the serum/plasma. The study aimed to investigate how hemolysis affects the results of GH and IGF-1 samples on the Immulite 2000 XPi. The results will determine the routines for hemolytic samples for GH or IGF-1 at Örebro University Hospital. Hemolysis was produced and added to various serum samples with low and high levels of GH and IGF-1 to obtain samples with varying degrees of hemolysis. The results showed that increasing hemolysis index correlates with GH and IGF-1 concentrations, with the exception of low GH concentration, which did not show any correlation to hemolysis index. A 10% difference in GH and IGF-1 concentrations was achieved with an increase in hemolysis index of 555.40 mg/dL for GH and 333.3 mg/dL for IGF-1. Based on the results, the hemolysis limit was equivalent to the manufacturer's limits. Therefore, clinical chemistry at Örebro University Hospital can continue with current hemolysis limits.

En ökad utbredning av vankomycinresistenta enterokocker (VRE) har setts i Sverige sedan 2007. Bakteriemi orsakad av VRE är mycket svårbehandlad, varför snabbare tillförlitlig resistensdiagnostik är betydelsefullt för att minska dödlighet, vårdtider, vårdkostnader och belastning på sjukvårdssystemet. På mikrobiologilaboratoriet, Region Jönköpings län (RJL), tar idag identifiering av fenotypisk vankomycinresistens vid optimala förhållanden 6 timmar, räknat från att enterokocker konstaterats växa i blodet. Resistensgenerna vanA och vanB, som bland andra orsakar vankomycinresistens hos enterokocker, kan genetiskt verifieras med loop-mediated isothermal amplification men tar idag upp till ett dygn då bakteriekolonier används som analysmaterial i arbetsrutinen på molekylärbiologilaboratoriet, RJL. Syftet med studien var att utvärdera bakteriepellet som analysmaterial för genetisk identifiering av vanA och vanB, på Genie® II Mk2 med eazyplex® VRE basic, hos enterokocker från positiva blododlingar. För att utvärdera bakteriepellet som analysmaterial analyserades isolat av Enterococcus faecium (n=17) och Enterococcus faecalis (n=5) från bakteriepellets tillverkade från simulerade positiva blododlingar med eazyplex® VRE basic på Genie® II Mk2, varpå resultaten jämfördes mot isolatens faktiska närvaro/frånvaro av vanA/vanB. Samstämmigheten av de uppmätta- och de förväntade resultaten var fullständig, vilket indikerar att bakteriepellet med hög tillförlitlighet kan användas som analysmaterial till eazyplex® VRE basic för att påvisa vanA och vanB hos enterokocker i blododlingar. / An increased prevalence of vancomycin-resistant enterococci (VRE) has been observed in Sweden since 2007. Treating bacteremia caused by VRE is difficult, which is why faster, and reliable resistance diagnostics are important. At the Microbiology laboratory, Region Jönköping County, the identification of phenotypic vancomycin resistance under optimal conditions takes 6 hours from when growth of enterococci in blood is determined. The genes vanA and vanB, which among others cause vancomycin resistance, can be genetically verified by loop-mediated isothermal amplification, but takes up to one day since bacterial colonies are used as analysis material. The aim of the study was to evaluate bacterial pellet as an analytical material for genetic identification of vanA and vanB, on Genie® II Mk2 with eazyplex® VRE basic, in enterococci from positive blood cultures. To evaluate the bacterial pellet, isolates of Enterococcus faecium (n=17) and Enterococcus faecalis (n=5) from bacterial pellets made from simulated positive blood cultures were analyzed with eazyplex® VRE basic on the Genie® II Mk2, and the results were compared to the actual presence/absence of vanA/vanB in the isolates. The complete coherence between the expected and measured results indicates that the bacterial pellet can be used as an analytical material for eazyplex® VRE basic.

When performing sepsis diagnosis, the most important preanalytical variable is blood volume. Too little blood increases the risk for false negatives whereas overfilling causes increased risk for false positives. Even though this fact is known, there are case studies showing that in a majority of tests, the taken blood sample volume is not the recommended amount. As previously tried methods have been limited in their ability to tackle the problem this study aimed at creating a technical device to aid healthcare providers with blood volume sample collection. As a base, the double diamond approach by the Design Council was used. This design approach splits up the design process in four distinctly different phases (discover, define, develop, and deliver) all using their own methods to aid the creative process. After completing the discover and define phase it was determined that a non-contact capacitance liquid level sensor could operate as an ideal blood volume sample device. During the development and delivery phase prototypes were created and evaluated. The final results of this work could not give conclusive evidence concerning if a non-contact liquid level sensor could operate as an ideal blood volume collection device. The methodological approach used in this thesis can be used as inspiration for a designer to create a device for a similar or different purpose. Moreover, information from this thesis can also work as reference material to develop a device to perform ideal blood volume sample collection. Such a device would have the potential to be an essential part of the everyday workflow in sample collection from patients with sepsis worldwide and would aid in ensures effective and fast diagnostics.

Lactate is an important biomarker in sports and the lactate threshold concept is one of the best indicators of endurance performance in an athlete. However, to quantify the lactate threshold, an invasive method to take a blood sample must be used. Limitations for this method include stopping the active exercise for blood sampling and no real-time feedback. Instead, a novel non-invasive wearable biosensor can be used to measure the lactate concentration in sweat. The sensor generates an electrical current depending on the lactate concentration in the sweat, and therefore must an electronic device called a potentiostat be used to condition the current. However, available potentiostats are not suitable for use in sports where form factor, battery life and wireless connectivity is important. This thesis aims to solve this by developing a wearable device and software which can be used to measure the lactate concentration in sweat in real-time during exercise. The development process consisted of the determination of specifications, prototype development and thorough laboratory and on-body testing. Finally, a novel wearable device and software capable of real-time lactate measurements in sweat during exercise were presented. The device, called LactateStat, was 58mm ∗ 55mm ∗ 13mm, the current consumption was only 7.8mA, the current measurement resolution was 0.5 nA, the limit of detection was 0.45 nA and the current measurement range was around 750 μA. LactateStat is one of the first of its kind and provides a base for future development as the hardware, firmware and software resources are provided as open-source. / Laktat är en viktig biomarkör inom idrott och konceptet laktattröskel är en av de bästa indikatorerna för uthållighet hos en idrottsutövare. Men för att mäta laktattröskeln krävs en invasiv metod som går ut på att man tar ett blodprov. Begränsningarna med denna metod är bland annat att idrottsutövningen måste stoppas för att ta ett blodprov och att man inte får realtidsåterkoppling. I stället kan en liten och icke-invasiv bärbar biosensor användas för att mäta laktatkoncentrationen i svett. Sensorn genererar en elektrisk ström beroende på laktatkoncentrationen i svetten och en enhet som kallas potentiostat måste därför användas för att mäta denna ström. Tillgängliga potentiostater är dock inte lämpliga för användning inom sport där formfaktor, batteritid och trådlös kommunikation är viktigt. Denna avhandling har som syfte att lösa detta genom att utveckla en bärbar enhet och mjukvara som kan användas för att mäta laktatkoncentrationen i svett i realtid under träning. Utvecklingsprocessen bestod av bestämning av specifikationer, framtagning av en prototyp och noggrann laboratorie- och kroppstestning. Som resultat presenterades en banbrytande bärbar enhet och mjukvara som kan mäta laktat i realtid i svett under träning. Enheten, som kallades LactateStat, var 58mm * 55mm * 13mm, den aktiva strömförbrukningen var 7.8mA, den bästa mätupplösningen för ström var 0.5 nA, detektionsgränsen var 0.45 nA och det maximala mätområdet för ström var ca. 750 μA. LactateStat är en av de första i sitt slag och ger en bas för framtida utvecklingsarbete eftersom hårdvaru-, programvaru- och mjukvaruresurserna tillhandahålls som öppen källkod.

Vasopressin är ett viktigt hormon som har många fysiologiska funktioner, däribland upprätthållandet av vätskebalansen i kroppen. Mätning av detta hormon är dock komplicerat och därför används ”skuggfragmentet” copeptin, som härstammar från samma prekursor. Genom användandet av metoden B·R·A·H·M·S KRYPTOR compact PLUS mäts copeptin. Studiens syfte är att beräkna variations-koefficienten och därmed undersöka de uppmätta värdenas reproducerbarhet. Vidare blir syftet att använda EpiHealth-kohortstudien för att validera den redan kända kopplingen mellan copeptin och förhöjt blodsocker genom en multivariant linjär regression. Vi kan i arbetet konstatera att copeptin metoden har en god reproducerbarhet, där majoriteten av de multipelt uppmätta copeptin-värdena har en inter-assay CV <8%. Vid undersökning av EpiHealth-kohorten fann vi att en ökning av copeptin var kross-sektionellt associerad med ett flertal metabola riskmarkörer, däribland fastande plasma-glukos, efter multivariant justering. Att copeptin var signifikant relaterat till denna potenta metabola riskmarkör kan tyda på att det finns ett orsakssamband mellan förhöjt vasopressin och förhöjt blodsocker, något som även tidigare studier har pekat på. Detta i sin tur visar att vasopressin kan spela en roll i utvecklandet av typ 2-diabetes. Om ett orsaks-samband föreligger undersöks nu i en stor randomiserad klinisk studie där vasopressin-nivåerna hos hälften av deltagarna sänks med hjälp av ökat vatten-intag (H2O-metab-studien). Det finns förhoppningar om att användandet av copeptin skall kunna användas i klinisk verksamhet för att riskbedöma individer avseende kardiometabola sjukdomar (däribland typ 2-diabetes). / Vasopressin is an important hormone that has many physiological functions, including the maintenance of fluid balance in the body. Measurement of this hormone is however complicated and therefore the "shadow fragment" copeptin is used, which is derived from the same precursor. Using the BRAHMS copeptin proAVP KRYPTOR method, copeptin was measured in this study. The purpose of the study is to calculate the coefficient of variation, and thus examine the reproducibility of the measured values ​. Furthermore, the aim will be to use the EpiHealth cohort study was used to validate the link between copeptin and elevated blood sugar through a multivariate linear regression. The majority of the multiple measurements of copeptin values had an inter-assay CV <8%, which indicates that the method has a good reproducibility. Examination of the EpiHealth cohort revealed that elevated copeptin was cross-sectionally associated with a number of metabolic risk markers, including fasting plasma glucose, after multivariate adjustment, a finding that is in line with previous findings from epidemiological studies. The fact that copeptin was significantly related to this potent metabolic risk marker may indicate a causal role of the vasopressin system in elevated blood glucose and may play a role in the development of type 2 diabetes metillus. Previous experimental and genetical studies have indicated a causal association between elevated vasopressin and diabetes development. Currently, a randomized clinical trial is ongoing (the H2O-metab-study) in order to investigate a possible causal association between elevated vasopressin and glucose. In the study, increased water intake is used to lower plasma vasopressin (measured as copeptin), and the glucose-lowering potential of this water treatment is tested. There are hopes that copeptin can in the future be used in clinical practice for risk assessment with respect to cardiometabolic diseases (including type 2 diabetes).

The demand for the improvement of currently available tests for qualitative non-invasive diagnostic of COVID-19, i.e., the development of new methods for fast, low-cost and accurate tests for the conformation of SARS-CoV-2, is increasing rapidly. Among many different approaches, electrochemical biosensors, which have the capability of miniaturization and could be available globally in most remote areas, may also help in avoiding the transmission of COVID-19 disease. When properly designed, electrochemical tests might have higher sensitivity, specificity, and accuracy, which is very important for COVID-19 diagnostics. In this work a saliva based electrochemical biosensor developed for COVID-19 detection was tested using real human samples. First, 41 saliva samples from volunteers were collected during January-February 2022, when the rate of SARS-CoV-2 infection was the highest in Skåne region, Sweden. Second, cyclic voltammograms of SARS-CoV-2 biomodified electrodes were recorded in buffers with and without SARS-CoV-2 positive control, as well as in saliva samples. Third, the samples were analyzed using commercially available COVID-19 salivary tests, viz., rapid antigen test and RT-qPCR (quantitative reverse transcription polymerase chain reaction). It was shown that 8 samples were collected from COVID-19 positive volunteers. Based on the analysis of all experimental results it was concluded that compared to rapid antigen and RT-qPCR tests, the sensitivity and reproducibility of the biosensor is not enough for real practical applications. Thus, some suggestions for further improvement of basic parameters of the developed biodevice were made. / <p>x</p> / x

ABO- och Rh-systemet är de mest kliniskt betydelsefulla blodgruppssystem för nutidens serologiska diagnostik. En viktig analysmetod inom detta område är kvantifiering av blodgruppsantikroppar då mängden antikroppar i plasma bestäms. Denna metod har flera olika användningsområden, bland annat för att bestämma mängden av irreguljära antikroppar för gravida vid immunisering då mamman har bildat antikroppar mot ett antigen som fostret har. Metoden utförs även i samband med transplantationer och för trombocytgivare. Kvantifiering av blodgruppsantikroppar kan utföras både manuellt och automatiskt. Den manuella metoden utförs med diluent pH7, en form av fosfatbuffrad saltlösning (PBS), som spädningsvätska, medan den automatiska utförs med en dyrare titreringslösning. Ett mer kostnadseffektivt val skulle vara att använda diluent pH7 som spädningsvätska för den automatiska metoden. Denna studie är en metodoptimering för automatisk titrering av blodgruppsantikroppar med IH-500 instrument. Plasmaprover från tre olika kategorier av individer (transplantationspatienter, trombocytgivare och gravida kvinnor) analyserades på IH-500 instrument för både ABO- och andra blodgruppsantikroppar. I maskinen utförs en spädningsserie av plasma från patienter och efter tillsättning av testerytrocyter observeras var det skett en agglutination och hur starkt den var. Det första spädningssteget som graderas som 1+ reaktion räknas som antikroppstitern. Resultat redovisades i form av stapeldiagram som visar skillnaden i antikroppstiter med både titreringslösning och PBS som spädningsvätska. Samtliga resultat ligger inom ramen för vad som definierats som ett godkänt resultat. Konklusionen av studien är att PBS är ett effektivt och billigare alternativ som kan användas som spädningsvätska vid automatisk titrering av ABO- och andra blodgruppsantikroppar på IH-500 instrument. / The ABO and Rh blood group systems are the most clinically significant blood group systems for contemporary serological diagnostics. A vital analysis method in this area is the quantification of blood group antibodies, where the amount of antibodies in plasma is determined. This method has several different uses, including the determination of irregular antibodies in pregnant women suspected of immunization if the mother has developed antibodies against an antigen that the fetus possesses. The method is also performed in connection with transplants and for platelet donors. Quantification of blood group antibodies can be performed both manually and automatically. The manual method utilizes diluent pH7, a form of phosphate-buffered saline (PBS), as the diluent, while the automatic method is performed with a more expensive titration solution. A more cost-effective choice would be to use diluent pH7 as the diluent for the automatic method. This study aims to optimize the method for automatic titration of blood group antibodies using the IH-500 instrument. Plasma samples from three different categories of individuals (transplant patients, platelet donors and pregnant women) were analyzed on the IH-500 instrument for both ABO and other blood group antibodies. From patient plasma samples a dilution series was made, and after adding test erythrocytes the level of agglutination was observed. The first dilution step graded as 1+ reaction is counted as the antibody titer. Results were presented in the form of bar graphs illustrating the difference in antibody titers with both titration solution and PBS as the diluent. All results fall within the range of what has been defined as an acceptable result. The conclusion of the study is that PBS is an effective and inexpensive alternative that can be used as the diluent for automatic titration of ABO and other blood group antibodies on the IH-500 instrument.

The mastoid, located in the temporal bone, houses an air cell system whose cells have a variation in size that can go far below current conventional clinical CT scanner resolution. Therefore, the mastoid air cell system is only partially represented in a CT scan. Where the conventional clinical CT scanner lacks level of minute details, micro-CT scanning provides an overwhelming amount of ne details. The temporal bone being one of the most complex in the human body, visualization of micro-CT scanning of this boneawakens the curiosity of the experimenter, especially with the correct visualization settings. This thesis first presents a statistical analysis determining the surface area to volume ratio of the mastoid air cell system of human temporal bone, from micro-CT scanning using methods previously applied for conventional clinical CT scans. The study compared current results with previous studies, with successive downsampling the data down to a resolution found in conventional clinical CT scanning. The results from the statistical analysis showed that all the small mastoid air cells, that cannot be detected in conventional clinical CT scans, do heavily contribute to the estimation of the surface area, and in consequence to the estimation of the surface area to volume ratio by a factor of about 2.6. Such a result further strengthens the idea of the mastoid to play an active role in pressure regulation and gas exchange. Discovery of micro-channels through specific use of a non-traditional transfer function was then reported, where a qualitative and a quantitative pre-analysis were performed and reported. To gain more knowledge about these micro-channels, a local structure tensor analysis was applied where structures are described in terms of planar, tubular, or isotropic structures. The results from this structural tensor analysis suggest these microchannels to potentially be part of a more complex framework, which hypothetically would provide a separate blood supply for the mucosa lining the mastoid air cell system. The knowledge gained from analysing the micro-channels as locally providing blood to the mucosa, led to the consideration of how inflammation of the mucosa could impact the pneumatization of the mastoid air cell system. Though very primitive, a 3D shape analysis of the mastoid air cell system was carried out. The mastoid air cell system was first represented in a compact form through a medial axis, from which medial balls could be used. The medial balls, representative of how large the mastoid air cells can be locally, were used in two complementary clustering methods, one based on the size diameter of the medial balls and one based on their location within the mastoid air cell system. From both quantitative and qualitative statistics, it was possible to map the clusters based on pre-defined regions already described in the literature, which opened the door for new hypotheses concerning the effect of mucosal inflammation on the mastoid pneumatization. Last but not least, discovery of other structures, previously unreported in the literature, were also visually observed and briefly discussed in this thesis. Further analysis of these unknown structures is needed.

Heart failure is a term for a group of complex symtoms characterized by reduced heart function. One of these syndromes, referred to as heart failure with preserved ejection fraction (HFpEF), has increased in prevalence compared to other types of heart failures during the recent years. A concern is the difficulty in diagnosing patients with HFpEF, since current tools are considered insufficient. The aim of this thesis was to examine Peak Oxygen Uptake (VO2peak) in relation to Total Heart Volume (THV) among heart failure patients with preserved ejection fraction (HFpEF, EF &gt;40 %) compared to healthy controls. THV was acquired by delineating images acquired using cardiovascular magnetic resonance imaging, while VO2peak was measured in oxygen curves acquired from cardiopulmonary exercise tests. Ratios were calculated by dividing VO2peak with THV. In order to determine if blood hemoglobin concentration (b-Hb) could affect the ratio, ratios were adjusted to b-Hb using an adjusting factor. Mean THV was nearly 250 ml larger in HFpEF patients compared to the controls. Patients’ mean VO2peak was more than 1000 ml lower compared to the controls. Mean VO2peak/THV ratio calculated for the patients were less than half of that calculated for the controls. Adjusting the ratio to b-Hb did not affect the ratios significantly. The study was limited by the size of the test group, but the findings suggest that a VO2peak/THV ratio can be used to separate HFpEF patients from healthy controls. / Hjärtsvikt är ett begrepp för en grupp med komplexa symtom och kännetecknas av försämrad hjärtfunktion. Ett av dessa syndrom, hjärtsvikt med bevarad ejektionsfraktion (HFpEF), har ökat i prevalens jämfört med andra varianter av hjärtsvikt under de senaste åren. Ett problem är de svårigheter som finns med att diagnosticera patienter med HFpEF, då nuvarande verktyg inte är tillräckliga. Syftet med detta examensarbete var att undersöka maximalt syreupptag (VO2peak) i förhållande till total hjärtvolym (THV) bland hjärtsviktspatienter med bevarad ejektionsfraktion (HFpEF, EF &gt;40 %) jämfört med friska kontroller. THV erhölls genom att utlinjera bilder tagna med hjälp av magnetisk resonanstomografi, medan VO2peak mättes i syrevolymkurvor som registrerats under ergospirometri-undersökningar. Index beräknades genom att dividera VO2peak med THV. För att undersöka huruvida halten hemoglobin i blodet (b-Hb) kunde påverka index justerades index mot b-Hb med hjälp av en justeringsfaktor. Medel-THV var nästan 250 ml större hos HFpEF-patienter jämfört med kontroller. Medel-VO2peak var mer än 1000 ml lägre hos patienterna jämfört med kontroller. Medel VO2peak/THV-index som beräknats för patienter var mindre än hälften så högt som index beräknat för kontroller. Att justera index mot b-Hb påverkade inte index signifikant. Studien begränsades av mängden deltagare, men fynden indikerar att VO2peak/THV-index kan användas för att skilja HFpEF-patienter från friska kontroller.

Bakgrund: I slutet av 2019 upptäcktes flertalet fall av pneumoni av okänd etiologi i Wuhan, Kina. Efter isolering och sekvensering framkom det att det rörde sig om ett coronavirus, benämnt SARS-CoV-2. Sociala restriktioner och munskydd har inte lyckats stoppa denna pandemi, och hoppet ligger nu på de olika vaccinkandidater som började utvecklas under 2020. Syfte: Syftet var att jämföra olika vaccins effektivitet och förekomst av olika biverkningar. Metod: En systemisk litteraturstudie utfördes, där en sökning i Pubmed utfördes och fyra artiklar valdes ut till arbetet för att jämföra vaccineffektivitet och biverkningar för de tre vaccin som var godkända av läkemedelsverket i februari. Resultat: Pfizer/BioNTechs mRNA-vaccin hade en effektivitet på 94,8%, Modernas mRNA-vaccin en effektivitet på 94,1% och Oxford-AstraZenecas vektorvaccin uppvisade en effektivitet på 70,4%. De vanligaste biverkningarna vid vaccinering var smärta vid injektionsplatsen, huvudvärk samt utmattning. Slutsats: En tillfredsställande jämförelse kunde inte genomföras då de olika fas III studierna utfördes på olika åldersgrupper och i olika delar av världen där SARS-CoV-2 mutationerna skiljde sig åt, vilket kan ha påverkat resultaten. / Background: At the end of 2019, several cases of pneumonia of unknown ethology were discovered in Wuhan, China. After isolating and sequencing the pathogen it became apparent that it was a Coronavirus, named SARS-CoV-2. Social restrictions and mask wearing mandates have not managed to stop this pandemic, and the hope lies with the different vaccine candidates that started to be developed during 2020. Aim: The aim was to compare different vaccines efficacy and prevalence of side effects. Method: A systemic literature study was implemented, the search was done in Pubmed and four papers were selected to compare vaccine efficacy and side effects for the three vaccines that were approved by Läkemedelsverket in February. Results: Pfizer/BioNTech’s mRNA-vaccine showed an efficacy of 94,8%, Moderna’s an efficacy of 94,1% and Oxford-AstraZeneca’s vector vaccine showed an efficacy of 70,4%. The most common side effects following vaccination was pain at the site of injection, headache and fatigue. Conclusion: A satisfying comparison could not be achieved since the different phase III studies were performed on different age groups and in different parts of the world where SARS-CoV-2 mutations differ, which could impact the results.