SARS-CoV-2 specific immune responses in overweight and obese COVID-19 patients

Obesity is a known risk factor for severe respiratory tract infections. In this prospective study, we assessed the impact of being obese or overweight on longitudinal SARS-CoV-2 humoral and cellular responses up to 18 months after infection. 274 patients provided blood samples at regular time intervals up to 18 months including obese (BMI ≥30, n=32), overweight (BMI 25-29.9, n=103) and normal body weight (BMI 18.5-24.9, n=134) SARS-CoV-2 patients. We determined SARS-CoV-2 spike-specific IgG, IgA, IgM levels by ELISA and neutralising antibody titres by neutralisation assay. RBD- and spike-specific memory B cells were investigated by ELISpot, spike- and non-spike-specific IFN-γ, IL-2 and IFN-γ/IL-2 secreting T cells by FluoroSpot and T cell receptor (TCR) sequencing was performed. Higher BMI correlated with increased COVID-19 severity. Humoral and cellular responses were stronger in overweight and obese patients than normal weight patients and associated with higher spike-specific IgG binding titres relative to neutralising antibody titres. Linear regression models demonstrated that BMI, age and COVID-19 severity correlated independently with higher SARS-CoV-2 immune responses. We found an increased proportion of unique SARS-CoV-2 specific T cell clonotypes after infection in overweight and obese patients. COVID-19 vaccination boosted humoral and cellular responses irrespective of BMI, although stronger immune boosting was observed in normal weight patients. Overall, our results highlight more severe disease and an over-reactivity of the immune system in overweight and obese patients after SARS-CoV-2 infection, underscoring the importance of recognizing overweight/obese individuals as a risk group for prioritisation for COVID-19 vaccination

Å være søsken til et barn med autisme

Mål: Målet med denne studien var å belyse hvordan det kan oppleves å være søsken til barn med autisme, nærmere bestemt hvordan det å ha søsken med autisme påvirker relasjonen til viktige andre. Metode: Det ble gjennomført kvalitative intervju av 4 ungdommer, 3 jenter og 1 gutt i alderen 14-17 år. Alle var søsken av et barn med autisme. De transkriberte lydbåndopptakene ble analysert hovedsakelig ved hjelp av systematisk tekstkondensering. Resultater: Alle informantene beskrev mor som en viktig støtteperson i sine liv. De snakket ikke like mye om far. Det kom også frem at informantene unngikk konfrontasjoner med sitt søsken med autisme, noen ved å føye sitt søskens ønsker og behov, andre ved å ikke gjenta spørsmål, eller ved å ha spesielle rutiner i hjemmet. Informantene hadde også ulike tanker om sin og sitt søskens fremtid. Noen var bekymret, andre hadde et mer positivt fremtidssyn. Mellom informantene var det varierende hvor mye oppmerksomhet de rapporterte å få fra sine foreldre sammenlignet med sitt søsken med autisme. Noen rapporterte at de fikk mindre oppmerksomhet, mens en beskrev å få mer oppmerksomhet enn sitt søsken med autisme. Konklusjon: Studien viser at det er noen felles temaer som er viktige for disse søsknene, og at de har en hverdag preget av erfaringer og problemstillinger andre ungdommer ikke nødvendigvis har eller kjenner til. Videre viser studien at det er behov for mer arbeid for å forstå hvordan det er å være søsken til et barn med autisme, og for å kartlegge behov for støttetilbud for disse søsknene

Mellom innordning og kunstnerisk frihet : en studie av Bronzinos maleri "Kristus i Limbo"

Oppgaven behandler ikonografi og malerstil i Bronzinos maleri ”Kristus i Limbo” i lys av motivhistoriske- og skriftlige kilder samt kulturhistoriske kontekster. Bronzino var like sentral som poet som maler. Hans malerier, spesielt hans religiøse motiv, er regnet for å være vanskelig å forstå. Jeg redegjør for hvordan Bronzino bruker allegorier og tvetydigheter i poesien, noe som etter min mening kan være en døråpner til flere tolkningsmuligheter av ”Kristus i Limbo”. Manerismen var i stor grad en omforming av renessansekunsten, der kunstnerne brukte sitater og kopiering av de store mestrenes verk, særlig av Michelangelo. Bronzino antyder ofte referanser til eksterne kilder, i stedet for å bruke direkte referanser og sitater, som han omformer og gir en ny mening. Oppgaveteksten behandler motivet ”Kristus i Limbo” i relasjon til noen aktuelle renessansemotiver. Særlig blir motivets referanser til Dommedagsfresken vektlagt. Jeg argumenterer for en mulig tolkning av motivet i lys av Dommedagsfreskens ideologi, som Valerie Shrimplin ser i relasjon til Marsilio Ficinos nyplatonisme. Den formale likheten Kristus-figuren og Eva-figuren i motivet har til Kristus-figuren og Jomfru Maria i Dommedagsfresken ligger til grunn for denne tolkningsmuligheten. Bronzino var aktiv medlem av Accademia Fiorentina, som var tverrfaglig sammensatt av utøvere innen kunstartene poesi, malerkunst og skulpturkunst. Dantes Den Guddommelige Komedie var et sentralt verk ved akademiet som Bronzino selv har uttalt at han kunne utenat. Komedien er en sentral skriftlig kilde som jeg analyserer motivet i forhold til. Forskningslitteraturen ser motivet ”Kristus i Limbo” i relasjon til beskrivelsen av Limbo i Komedien. Med den inngående kjennskapen Bronzino hadde til Dantes verk, stiller jeg spørsmål ved om motivet har en bredere referanse til verket. Sett i lys av hvordan Bronzino bruker referanser til eksterne kilder i sine dikt, kan detaljer i motivet tyde på at dette. Bronzino malte sitt motiv ”Kristus i Limbo” i en periode da Firenze gjennomgikk et paradigmeskifte. Cosimo I de’Medicis enevelde preget utformingen av billedkunsten, en påvirkning som både skjedde gjennom tilknytningen kunstnerne hadde til hoffet samt gjennom tilknytningen de hadde til de to statlige akademiene Accademia Fiorentina og Accademia del Disegno. Jeg analyserer motivet i relasjon til restriksjonene hoffet og akademiene la på dekorum. ”Kristus i Limbo” representerer en brytning i Bronzinos malerstil som vi kan se i relasjon til hans tidligere eksperimentelle periode og malerstilen som preger hans seneste motiv. Brytningen diskuterer jeg i forhold til mot-reformasjonens billeddekret som fikk økt innflytelse på utformingen av billedkunsten i siste halvdel av 1500-tallet i Firenze. Selv om påvirkningen fra mot-reformasjonen spesielt preger de religiøse motivene Bronzino malte etter 1552, kommer de også til uttrykk i komposisjon og malerstil i ”Kristus i Limbo”

Nettverkssentralitet og lønnsomhet i norske selskap 2006 - 2015. En empirisk studie av kjennetegn ved nettverksstruktur og drivere av sentralitet

Denne masteroppgaven studerer sammenhengen mellom nettverkssentralitet og lønnsomhet i 150 norske ikke-finansielle allmennaksjeselskap i perioden 2006 – 2015. Studiens bidrag er å vise strukturen i nettverk for ikke-finansielle allmennaksjeselskap og belyse forholdet mellom overlappende styreverv og lønnsomhet, hvor sentralitet er beregnet med utgangspunkt i antall (overlappende) styreverv. Vi bruker sosial nettverksanalyse for å illustrere utviklingen, og anvender paneldata for regresjonsformål. Våre funn peker i retning av at det ikke eksisterer noen sammenheng mellom nettverkssentralitet og lønnsomhet for ikke-finansielle allmennaksjeselskap i perioden 2006 – 2015. Resultatene kan tyde på at det er oppstått sentralitetsscore som går i favør av kvinnene i utvalget etter innføringen av lovpålagt kjønnskvotering i norske allmennaksjeselskap. Drivere for sentralitet i vår studie ser i hovedsak ut til å være at et selskap er børsnotert, samt at selskapet er opprettet og/eller omformet til allmennaksjeselskap i løpet av perioden vi undersøker. I tillegg ser det ut til at et selskaps risiko og størrelse har påvirkning – Dess mindre risiko tilknyttet selskapet og dess større det er, dess økt sannsynlighet for høyere score på sentralitet i vårt utvalg

Topical treatment with fresh human milk versus emollient on atopic eczema spots in young children: a small, randomized, split body, controlled, blinded pilot study

Background Public health nurses report on effects of fresh human milk as treatment for conjunctivitis, rhinitis and atopic eczema (AE), the latter being highly prevalent in early childhood. Emollients and topical corticosteroids are first line treatment of AE. As many caregivers have steroid phobia, alternative treatment options for mild AE are of interest. The aim of this small pilot study was to assess the potential effects and risks of applying fresh human milk locally on eczema spots in children with AE. Methods This was a split body, controlled, randomized and physician blinded pilot study, of children with AE with two similar contralateral eczema spots having a mother breastfeeding the child or a sibling. Fresh expressed milk and emollient was applied on the intervention spot and emollient alone on the control area, three times a day for four weeks. The severity and area of the eczema spots was evaluated weekly, and samples from milk and the spots were analysed weekly with respect to bacterial colonisation. Results Of nine patients included, six completed the study. Mean age at inclusion was 18.5 months. The spots examined were localized on the arms, legs or cheeks. The spots were similar in severity, but differed in area. In one patient the eczema ceased after inclusion. In four patients both control and intervention areas increased during the intervention. The relative change in eczema area compared to baseline showed less increase in the intervention spots in two patients, whereas the opposite was observed in three. In four children Staphylococcus aureus was found in their eczema once or more. In three of the 28 human milk samples, Staphylococcus aureus, alfa haemolytic streptococci or coagulase negative staphylococci were detected. Staphylococcus aureus was found once both in human milk and in the eczema spots, no clinical signs of infection were however observed. No secondary infection due to milk application was detected. Conclusion In this small pilot study, no effect was found on eczema spots treated with topical application of fresh human milk. (ClinicalTrials.gov Identifier, NCT02381028 )

Experimental Infection of Human Volunteers with the Heat-Stable Enterotoxin-Producing Enterotoxigenic Escherichia coli Strain TW11681

Infection with enterotoxigenic Escherichia coli (ETEC) producing the heat-stable enterotoxin (ST) is one of the most important causes of childhood diarrhoea in low- and middle-income countries. Here, we undertook a controlled human infection model (CHIM) study to investigate whether ST-producing ETEC strain TW11681 would be suitable for testing the protective efficacy of new ST-based vaccine candidates in vaccine challenge models. In groups of three, nine volunteers ingested 1 × 106, 1 × 107, or 1 × 108 colony-forming units (CFU) of TW11681. Flow cytometry-based assays were used to measure CD4+ T cell responses and antibody levels targeting virulence factors expressed by the strain. We found that infection with TW11681 elicited few and mild symptoms, including mild diarrhoea in two volunteers, both of whom ingested 1 × 106 CFU. Averaged across all volunteers, the CD4+ T cell responses specific for E. coli YghJ mucinase peaked 10 days after infection (3.2-fold (p = 0.016)), while the CD4+ T cell responses specific for Colonization Factor Antigen I (CFA/I) major fimbrial subunit (CfaB) peaked after 28 days (3.6-fold (p = 0.063)). The serum CfaB-specific anti-IgA and anti-IgG/IgM levels were significantly increased and peaked 3 months after infection. Both remained elevated for the duration of the 12-month follow-up. The corresponding anti-YghJ serological response was strongest after 10 days, although a significant increase was seen only for IgA levels (3.2-fold (p = 0.008)). In conclusion, due to its low diarrhoea attack risk, TW11681 is probably not suitable for testing the efficacy of new vaccines in human challenge studies at doses 1 × 106 to 1 × 108. However, the strain may still be useful in CHIMs for studying ETEC host-pathogen interactions

Experimental Infection of Human Volunteers with the Heat-Stable Enterotoxin-Producing Enterotoxigenic Escherichia coli Strain TW11681

Infection with enterotoxigenic Escherichia coli (ETEC) producing the heat-stable enterotoxin (ST) is one of the most important causes of childhood diarrhoea in low- and middle-income countries. Here, we undertook a controlled human infection model (CHIM) study to investigate whether ST-producing ETEC strain TW11681 would be suitable for testing the protective efficacy of new ST-based vaccine candidates in vaccine challenge models. In groups of three, nine volunteers ingested 1 × 106, 1 × 107, or 1 × 108 colony-forming units (CFU) of TW11681. Flow cytometry-based assays were used to measure CD4+ T cell responses and antibody levels targeting virulence factors expressed by the strain. We found that infection with TW11681 elicited few and mild symptoms, including mild diarrhoea in two volunteers, both of whom ingested 1 × 106 CFU. Averaged across all volunteers, the CD4+ T cell responses specific for E. coli YghJ mucinase peaked 10 days after infection (3.2-fold (p = 0.016)), while the CD4+ T cell responses specific for Colonization Factor Antigen I (CFA/I) major fimbrial subunit (CfaB) peaked after 28 days (3.6-fold (p = 0.063)). The serum CfaB-specific anti-IgA and anti-IgG/IgM levels were significantly increased and peaked 3 months after infection. Both remained elevated for the duration of the 12-month follow-up. The corresponding anti-YghJ serological response was strongest after 10 days, although a significant increase was seen only for IgA levels (3.2-fold (p = 0.008)). In conclusion, due to its low diarrhoea attack risk, TW11681 is probably not suitable for testing the efficacy of new vaccines in human challenge studies at doses 1 × 106 to 1 × 108. However, the strain may still be useful in CHIMs for studying ETEC host-pathogen interactions

Durable immune responses after BNT162b2 vaccination in home-dwelling old adults

Objectives: Elderly are an understudied, high-risk group vulnerable to severe COVID-19. We comprehensively analyzed the durability of humoral and cellular immune responses after BNT162b2 vaccination and SARS-CoV-2 infection in elderly and younger adults. Methods: Home-dwelling old (n = 100, median 86 years) and younger adults (n = 449, median 38 years) were vaccinated with two doses of BNT162b2 vaccine at 3-week intervals and followed for 9-months. Vaccine-induced responses were compared to home-isolated COVID-19 patients (n = 183, median 47 years). Our analysis included neutralizing antibodies, spike-specific IgG, memory B-cells, IFN-γ and IL-2 secreting T-cells and sequencing of the T-cell receptor (TCR) repertoire. Results: Spike-specific breadth and depth of the CD4+ and CD8+ TCR repertoires were significantly lower in the elderly after one and two vaccinations. Both vaccinations boosted IFN-γ and IL-2 secreting spike-specific T-cells responses, with 96 % of the elderly and 100 % of the younger adults responding after the second dose, although responses were not maintained at 9-months. In contrast, T-cell responses persisted up to 12-months in infected patients. Spike-specific memory B-cells were induced after the first dose in 87 % of the younger adults compared to 38 % of the elderly, which increased to 83 % after the second dose. Memory B-cells were maintained at 9-months post-vaccination in both vaccination groups. Neutralizing antibody titers were estimated to last for 1-year in younger adults but only 6-months in the older vaccinees. Interestingly, infected older patients (n = 15, median 75 years) had more durable neutralizing titers estimated to last 14-months, 8-months longer than the older vaccinees. Conclusions: Vaccine-induced spike-specific IgG and neutralizing antibodies were consistently lower in the older than younger vaccinees. Overall, our data provide valuable insights into the kinetics of the humoral and cellular immune response in the elderly after SARS-CoV-2 vaccination or infection, highlighting the need for two doses, which can guide future vaccine design.Clinical trials.gov; NCT04706390