Changes in vitamins and trace elements after initiation of highly effective CFTR modulator therapy in children and adults with cystic fibrosis - a real-life insight.

BACKGROUND: Highly-effective CFTR-modulator therapy with elexa-/teza-/ivacaftor (ETI) has led to improvements in pulmonary outcomes, sweat chloride, body mass index (BMI) and quality of life in people with cystic fibrosis (CF). Improved uptake of fat-soluble vitamins and micronutrients has been reported for CFTR-modulators but data regarding ETI therapy is lacking. METHODS: This single-center retrospective study evaluated forced expiratory volume in one second (FEV-1), sweat chloride, BMI, transaminases (AST, ALT), bilirubin, vitamins A, D, E, zinc and selenium in children and adults eligible for ETI. Parameters were assessed before and up to one year after initiation of ETI. RESULTS: 58 patients (median age m = 28 years, SD ± 11.6 years, 51.7% female14 < 18 years old) were included. FEV-1 and sweat chloride improved significantly after ETI. There were no changes in BMI or AST. ALT was increased significantly after 4 weeks of ETI but returned to normal levels in further course. Bilirubin levels remained elevated after ETI. Vitamin A was significantly higher 12 months after ETI. No changes were found for vitamins D, E, zinc and selenium. CONCLUSIONS: This study adds to the evidence that improvements of some fat-soluble vitamin levels can be found after ETI. No changes regarding micronutrients were noted. Individualized follow-up and supplementation are recommended.

Characterization of adolescents with functional respiratory disorders and prior history of SARS-CoV-2.

BACKGROUND: The SARS-CoV-2 pandemic has caused significant pulmonary morbidity and mortality in the adult population. Children and adolescents typically show milder symptoms; however, a relevant proportion of them report persistent pulmonary symptoms even after mild SARS-CoV-2 infection. Functional respiratory disorders may be relevant differential diagnoses of persistent dyspnea. This study aims at characterizing functional respiratory disorders that may arise after SARS-CoV-2 infection regarding their clinical presentation and pulmonary function tests as well as gaining insights into the clinical course after initiation of appropriate therapy. METHODS: This study retrospectively identified all patients referred to an outpatient clinic for pediatric pulmonology with functional respiratory disorders manifesting after proven SARS-CoV-2 infection between January 1, 2022, and October 31, 2022. Clinical history, thorough clinical examination regarding breathing patterns, and pulmonary function tests (PFTs) were taken into consideration to diagnose functional respiratory disorders. RESULTS: Twenty-five patients (44% female) with mean (m) age = 12.73 years (SD ± 1.86) who showed distinctive features of functional respiratory disorders after SARS-CoV-2 infection (onset at m = 4.15 (± 4.24) weeks after infection) were identified. Eleven patients showed thoracic dominant breathing with insufficient ventilation, and 4 patients mainly had symptoms of inducible laryngeal obstruction. The rest (n = 10) showed overlap of these two etiologies. Most patients had a flattened inspiratory curve on spirometry and slightly elevated residual volume on body plethysmography, but values of PFTs were normal before and after standardized treadmill exercise testing. Patients were educated about the benign nature of the condition and were offered rebreathing training. All patients with follow-up (n = 5) showed normalization of the breathing pattern within 3 months. CONCLUSIONS: Functional respiratory disorders are important differential diagnoses in persisting post-SARS-CoV-2 dyspnea in adolescents. A combination of clinical history, detailed examination of breathing patterns, and pulmonary function tests are helpful to correctly diagnose these conditions. Reassurance and rebreathing training are the mainstay of the therapy. The clinical course is favorable.

Phorbol-12-myristate-13-acetate is a potent enhancer of B cells with a granzyme B+ regulatory phenotype.

Introduction: The infusion of ex-vivo-generated regulatory B cells may represent a promising novel therapeutic approach for a variety of autoimmune and hyperinflammatory conditions including graft-versus-host disease. Methods: Previously, we developed a protocol for the generation of a novel population of regulatory B cells, which are characterized by secretion of enzymatically active granzyme B (GraB cells). This protocol uses recombinant interleukin 21 (IL-21) and goat-derived F(ab)'2 fragments against the human B cell receptor (anti-BCR). Generally, the use of xenogeneic material for the manufacturing of advanced therapy medicinal products should be avoided to prevent adverse immune reactions as well as potential transmission of so far unknown diseases. Results: In the present work we demonstrated that phorbol-12-myristate-13-acetate (PMA/TPA), a phorbol ester with a particular analogy to the second messenger diacylglycerol (DAG), is a potent enhancer of IL-21-induced differentiation of pre-activated B cells into GraB cells. The percentage of GraB cells after stimulation of pre-activated B cells with IL-21 and PMA/TPA was not significantly lower compared to stimulation with IL-21 and anti-BCR. Discussion: Given that PMA/TPA has already undergone encouraging clinical testing in patients with certain haematological diseases, our results suggest that PMA/TPA may be a safe and feasible alternative for ex-vivo manufacturing of GraB cells.

Multimodal analysis of granulocytes, monocytes, and platelets in patients with cystic fibrosis before and after Elexacaftor-Tezacaftor-Ivacaftor treatment.

Cystic fibrosis (CF) is a monogenetic disease caused by an impairment of the cystic fibrosis transmembrane conductance regulator (CFTR). CF affects multiple organs and is associated with acute and chronic inflammation. In 2020, Elexacaftor-Tezacaftor-Ivacaftor (ETI) was approved to enhance and restore the remaining CFTR functionality. This study investigates cellular innate immunity, with a focus on neutrophil activation and phenotype, comparing healthy volunteers with patients with CF before (T1, n = 13) and after six months (T2, n = 11) of ETI treatment. ETI treatment reduced sweat chloride (T1: 95 mmol/l (83|108) vs. T2: 32 mmol/l (25|62), p < 0.01, median, first|third quartile) and significantly improved pulmonal function (FEV1 T1: 2.66 l (1.92|3.04) vs. T2: 3.69 l (3.00|4.03), p < 0.01). Moreover, there was a significant decrease in the biomarker human epididymis protein 4 (T1: 6.2 ng/ml (4.6|6.3) vs. T2: 3.0 ng/ml (2.2|3.7), p < 0.01) and a small but significant decrease in matrix metallopeptidase 9 (T1: 45.5 ng/ml (32.5|140.1) vs. T2: 28.2 ng/ml (18.2|33.6), p < 0.05). Neutrophil phenotype (CD10, CD11b, CD62L, and CD66b) and function (radical oxygen species generation, chemotactic and phagocytic activity) remained largely unaffected by ETI treatment. Likewise, monocyte phenotype and markers of platelet activation were similar at T1 and T2. In summary, the present study confirmed a positive impact on patients with CF after ETI treatment. However, neither beneficial nor harmful effects of ETI treatment on cellular innate immunity could be detected, possibly due to the study population consisting of patients with well-controlled CF.

Serum neutralizing capacity and T-cell response against the omicron BA.1 variant in seropositive children and their parents one year after SARS-CoV-2 infection.

Introduction: Durability of immune protection against reinfection with SARS-CoV-2 remains enigmatic, especially in the pediatric population and in the context of immune-evading variants of concern. Obviously, this knowledge is required for measures to contain the spread of infection and in selecting rational preventive measures. Methods: Here, we investigated the serum neutralization capacity of 36 seropositive adults and 34 children approximately one year after infection with the ancestral Wuhan strain of SARS-CoV-2 by using a pseudovirus neutralization assay. Results: We found that 88.9% of seropositive adult (32/36) and 94.1% of seropositive children (32/34) convalescents retained the neutralizing activity against the SARS-CoV-2 Wuhan strain (WT). Although, the neutralization effect against Omicron BA.1 (B.1.1.529.1) was significantly lower, 70.6% (24/34) of children and 41.7% (15/36) of adults possessed BA.1 cross-neutralizing antibodies. The spike 1 (S1)-specific T cell recall capacity using an activation-induced marker assay was analyzed in 18 adults and 16 children. All participants had detectable S1-specific CD4 T cells against WT, and 72.2% (13/18) adults and 81,3% (13/16) children had detectable S1 WT-specific CD8 T cells. CD4 cross-reactivity against BA.1 was demonstrated in all investigated adults (18/18), and 66.7% (12/18) adult participants had also detectable specific CD8 BA.1 T cells while we detected BA.1 S1 reactive CD4 and CD8 T cells in 81.3% (13/16) children. Discussion: Together, our findings demonstrate that infection with the ancestral strain of SARS-CoV-2 in children as well as in adults induces robust serological as well as T cell memory responses that persist over at least 12 months. This suggests persistent immunological memory and partial cross-reactivity against Omicron BA.1.

Effects of CFTR-modulator triple therapy on sinunasal symptoms in children and adults with cystic fibrosis.

PURPOSE: Sinunasal symptoms and chronic rhinusinutitis are common in patients with cystic fibrosis. Cystic fibrosis transmembrane regulator (CFTR) modulators have led to dramatic improvements of respiratory symptoms and quality of life in patients with cystic fibrosis. This study aims to evaluate subjective and objective sinunasal symptoms after start of CFTR-modulator triple therapy. METHODS: 43 patients (n = 6 < 18 years), treated with highly effective CFTR-modulator therapy with elexacaftor-tezacaftor-ivacaftor (ELX/TEZ/IVA) were included, as were 20 controls with cystic fibrosis but without CFTR-modulator therapy (n = 6 < 18 years). All assessed their sinunasal symptoms retrospectively and the intervention group at a mean of 9.3 (2-16) months after start of ELX/TEZ/IVA. RESULTS: Improvements in SNOT-22 overall score from m = 32.7 to m = 15.7 points (p < 0.0001) as well in the nasal, emotional, otologic, and sleep subdomains could be demonstrated in the intervention group. No changes were found in the control group. Children showed lower SNOT-22 scores than adults and a reduction of SNOT-22 total score from m = 9.4 to m = 2.2 (p = 0.25) was found. 8 patients were evaluated by an otorhinolaryngologist before and after start of ELX/TEZ/IVA and showed pronounced objective clinical improvement. CONCLUSIONS: Highly effective CFTR-modulator therapy has a significant positive impact on both subjective and objective sinunasal symptoms in patients with CF and some improvement could be demonstrated in children < 18 years as well.

Differentially induced immunity in buccal and nasal mucosae after vaccination for SARS-CoV-2: Prospects for mass scale immunity-screening in large populations.

Introduction: Humoral immunity after SARS-CoV-2 vaccination has been extensively investigated in blood. Aim of this study was to develop an ELISA method in order to determine the prevalence of IgG and IgA SARS-CoV-2 domain 1 spike-protein (S) specific antibodies (Abs) in buccal and nasal mucosal surfaces of vaccinees. Methods: To this end, we analyzed 69 individuals who received their first vaccine dose between February and July 2021. Vaccines administered were BNT162b2, mRNA-1273 or ChAdOx1-nCoV-19. Detection of IgG and IgA Abs was performed using commercial ELISA kits for both blood and swab samples after protocol modification for the latter. Results: Anti-spike IgG and IgA Abs in the buccal and/or nasal swabs were detectable in >81% of the study subjects after the second dose. The IgG measurements in buccal swabs appeared to correlate in a more consistent way with the respective measurements in blood with a correlation coefficient of r=0.74. It is of note that IgA Abs appeared to be significantly more prevalent in the nasal compared to the buccal mucosa. Optimal selection of the assay cut-off for the IgG antibody detection in buccal swabs conferred a sensitivity of 91.8% and a specificity of 100%. Last, individuals vaccinated with mRNA-based vaccines exhibited higher antibody levels in both blood and mucosal surfaces compared to those receiving ChAdOx1-nCoV-19 confirming previously reported results. Conclusion: In conclusion, our findings show a differential prevalence of anti-S Abs on mucosal surfaces after vaccination for SARS-CoV-2, while they also set the basis for potential future use of IgG antibody detection in buccal swabs for extended immunity screening in large populations.

High antibody levels and reduced cellular response in children up to one year after SARS-CoV-2 infection.

The COVID-19 course and immunity differ in children and adults. We analyzed immune response dynamics in 28 families up to 12 months after mild or asymptomatic infection. Unlike adults, the initial response is plasmablast-driven in children. Four months after infection, children show an enhanced specific antibody response and lower but detectable spike 1 protein (S1)-specific B and T cell responses than their parents. While specific antibodies decline, neutralizing antibody activity and breadth increase in both groups. The frequencies of S1-specific B and T cell responses remain stable. However, in children, one year after infection, an increase in the S1-specific IgA class switch and the expression of CD27 on S1-specific B cells and T cell maturation are observed. These results, together with the enhanced neutralizing potential and breadth of the specific antibodies, suggest a progressive maturation of the S1-specific immune response. Hence, the immune response in children persists over 12 months but dynamically changes in quality, with progressive neutralizing, breadth, and memory maturation. This implies a benefit for booster vaccination in children to consolidate memory formation.

Short-term effects of a novel bronchial drainage device: A pilot cohort study in subjects with cystic fibrosis.

Background and Aims: In cystic fibrosis (CF) airways, impaired airway mucociliary clearance and mucus accumulation due to cystic fibrosis transmembrane conductance regulator defects contribute to inflammation, progressive structural lung damage, and decline of lung function. Physiotherapy is essential to promote mucus mobilization and removal in CF and is a key element of rehabilitation measures, but conventional techniques may be suboptimal to mobilize viscous mucus. This study aimed to test the specific effects of a novel bronchial drainage device (BDD) (Simeox®; PhysioAssist) in subjects with CF and evaluate lung function, diaphragm mobility, and sputum properties. Methods: This prospective monocentric clinical cohort study in the setting of outpatient physiotherapy of CF patients (n = 21) with stable CF lung disease collected pulmonary lung function tests (PFT), diaphragm mobility, and sputum properties before and after two physiotherapy sessions using the novel BDD. PFT was assessed using spirometry and diaphragm mobility using m-mode ultrasound analysis. Spontaneous sputum samples were collected before and after using the BDD and analyzed for microstructure and DNA concentrations. Results: PFT parameters (FEV1, FVC, MEF25/50/75) were not affected by the use of the BDD. Ultrasound analysis of diaphragm mobility revealed an increase in maximum diaphragm excursion upon the intervention. Mucus analysis demonstrated altered microstructure and higher DNA concentrations collected after using the BDD compared to samples collected before. Pearson correlation analysis showed significant correlations between changes in mucus properties and DNA levels in respective mucus samples. Conclusion: Our results demonstrate that the novel BDD improves diaphragm mobility and alters sputum properties in subjects with CF. The novel BDD with unique properties may be further studied as a device in CF-specific physiotherapy to facilitate sputum mobilization of CF patients.

Long COVID symptoms in exposed and infected children, adolescents and their parents one year after SARS-CoV-2 infection: A prospective observational cohort study.

BACKGROUND: Long COVID in children and adolescents remains poorly understood due to a lack of well-controlled studies with long-term follow-up. In particular, the impact of the family context on persistent symptoms following SARS-CoV-2 infection remains unknown. We examined long COVID symptoms in a cohort of infected children, adolescents, and adults and their exposed but non-infected household members approximately 1 year after infection and investigated clustering of persistent symptoms within households. METHODS: 1267 members of 341 households (404 children aged <14 years, 140 adolescents aged 14-18 years and 723 adults) were categorized as having had either a SARS-CoV-2 infection or household exposure to SARS-CoV-2 without infection, based on three serological assays and history of laboratory-confirmed infection. Participants completed questionnaires assessing the presence of long COVID symptoms 11-12 months after infection in the household using online questionnaires. FINDINGS: The prevalence of moderate or severe persistent symptoms was statistically significantly higher in infected than in exposed women (36.4% [95% CI: 30.7-42.4%] vs 14.2% [95% CI: 8.7-21.5%]), infected men (22.9% [95% CI: 17.9-28.5%] vs 10.3% [95% CI: 5.8-16.9%]) and infected adolescent girls (32.1% 95% CI: 17.2-50.5%] vs 8.9% [95%CI: 3.1-19.8%]). However, moderate or severe persistent symptoms were not statistically more common in infected adolescent boys aged 14-18 (9.7% [95% CI: 2.8-23.6%] or in infected children <14 years (girls: 4.3% [95% CI: 1.2-11.0%]; boys: 3.7% [95% CI: 1.1-9.6%]) than in their exposed counterparts (adolescent boys: 0.0% [95% CI: 0.0-6.7%]; girls < 14 years: 2.3% [95% CI: 0·7-6·1%]; boys < 14 years: 0.0% [95% CI: 0.0-2.0%]). The number of persistent symptoms reported by individuals was associated with the number of persistent symptoms reported by their household members (IRR=1·11, p=·005, 95% CI [1.03-1.20]). INTERPRETATION: In this controlled, multi-centre study, infected men, women and adolescent girls were at increased risk of negative outcomes 11-12 months after SARS-CoV-2 infection. Amongst non-infected adults, prevalence of negative outcomes was also high. Prolonged symptoms tended to cluster within families, suggesting family-level interventions for long COVID could prove useful. FUNDING: Ministry of Science, Research and the Arts, Baden-Württemberg, Germany.

BNT162b2 Booster Vaccination Elicits Cross-Reactive Immunity Against SARS-CoV-2 Variants B.1.1.529 and B.1.617.2 in Convalescents of All Ages.

In this prospective observational cohort study we analyzed cellular and serological immune response parameters against SARS-CoV-2 and current variants of concern (VOC) in 147 COVID-19-convalescent and 39 COVID-19-naïve individuals before and after BNT162b2 booster vaccination. No significant differences regarding immunological response parameters were observed between younger and older individuals. Booster vaccination induced full recovery of both cellular and serological response parameters including IFN-γ secretion and anti-spike antibody titers with strong neutralization capacities against wild type SARS-COV-2 and Delta. Surprisingly, even serological neutralization capacity against Omicron was detectable one month after second vaccination and four months before it had been first observed in South Africa. As a result, more than 90% of convalescent individuals exhibited detectable and 75% strong Omicron neutralization capacity after booster vaccination, compared with 72% and 46% of COVID-19-naïve individuals. Our results support the notion that broad and cross-reactive immune memory against SARS-CoV-2 including currently known VOCs can be established by booster vaccination with spike-based mRNA vaccines like BNT162b2, particularly in COVID-19-convalescent individuals of all ages. Nevertheless, especially in COVID-19-naïve individuals future variants escaping the memory immune response may require vaccine approaches such as inactivated whole virus vaccines, which include all antigenic components of the virus.

Pulmonary Function and Persistent Clinical Symptoms in Children and Their Parents 12 Months After Mild SARS-CoV-2 Infection.

Background: Pulmonary involvement is the leading cause of morbidity and mortality after severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Long-term impairment has been reported in adults with severe infection. However, most infections cause only mild symptoms or are even asymptomatic, especially in children. There is insufficient evidence regarding pulmonary outcome measures in mild SARS-CoV-2. The objectives of this study were to determine spirometry parameters after SARS-CoV-2 infection and correlate those with reported persisting symptoms in children, adolescents, and adults. Methods: Data on clinical symptoms during acute infection as well as SARS-CoV-2 serology results were recorded. Twelve months after infection, spirometry was performed and information on persisting symptoms was collected using a structured questionnaire. 182 participants (108 SARS-CoV-2 positive) from 48 families were included; 53 children (< 14 years), 34 adolescents and young adults (14-25 years), and 95 adults. Results: Spirometry values did not significantly differ between the particular subgroups of the cohort (adults, adolescents, children; infected and non-infected individuals). Adults reported more symptoms during acute infection as well more persisting fatigue (29.7% of participants), reduced physical resilience (34.4%), and dyspnea (25.0%) 12 months after infection than adolescents (fatigue 26.7%, reduced physical resilience 20%, and 0% dyspnea) and children (4%, 0%, 0%, respectively). There was no correlation between persistent subjective symptoms and spirometry results. Discussion: Children and adolescents are less affected than adults by acute SARS-CoV-2 as well as by post-infection persistent symptoms. Spirometry was not able to demonstrate any differences between healthy individuals and participants who had suffered from mild SARS-CoV-2 12 months after the infection.

Role of ABO Blood Group in SARS-CoV-2 Infection in Households.

An association between certain ABO/Rh blood groups and susceptibility to SARS-CoV-2 infection has been proposed for adults, although this remains controversial. In children and adolescents, the relationship is unclear due to a lack of robust data. Here, we investigated the association of ABO/Rh blood groups and SARS-CoV-2 in a multi-center study comprising 163 households with 281 children and 355 adults and at least one SARS-CoV-2 seropositive individual as determined by three independent assays as a proxy for previous infection. In line with previous findings, we found a higher frequency of blood group A (+ 6%) and a lower frequency of blood group O (-6%) among the SARS-CoV-2 seropositive adults compared to the seronegative ones. This trend was not seen in children. In contrast, SARS-CoV-2 seropositive children had a significantly lower frequency of Rh-positive blood groups. ABO compatibility did not seem to play a role in SARS-CoV-2 transmission within the families. A correction for family clusters was performed and estimated fixed effects of the blood group on the risk of SARS-CoV-2 seropositivity and symptomatic infection were determined. Although we found a different distribution of blood groups in seropositive individuals compared to the reference population, the risk of SARS-CoV-2 seropositivity or symptomatic infection was not increased in children or in adults with blood group A or AB versus O or B. Increasing age was the only parameter positively correlating with the risk of SARS-CoV-2 infection. In conclusion, specific ABO/Rh blood groups and ABO compatibility appear not to predispose for SARS-CoV-2 susceptibility in children.

Robust and durable serological response following pediatric SARS-CoV-2 infection.

The quality and persistence of children's humoral immune response following SARS-CoV-2 infection remains largely unknown but will be crucial to guide pediatric SARS-CoV-2 vaccination programs. Here, we examine 548 children and 717 adults within 328 households with at least one member with a previous laboratory-confirmed SARS-CoV-2 infection. We assess serological response at 3-4 months and 11-12 months after infection using a bead-based multiplex immunoassay for 23 human coronavirus antigens including SARS-CoV-2 and its Variants of Concern (VOC) and endemic human coronaviruses (HCoVs), and additionally by three commercial SARS-CoV-2 antibody assays. Neutralization against wild type SARS-CoV-2 and the Delta VOC are analysed in a pseudotyped virus assay. Children, compared to adults, are five times more likely to be asymptomatic, and have higher specific antibody levels which persist longer (96.2% versus 82.9% still seropositive 11-12 months post infection). Of note, symptomatic and asymptomatic infections induce similar humoral responses in all age groups. SARS-CoV-2 infection occurs independent of HCoV serostatus. Neutralization responses of children and adults are similar, although neutralization is reduced for both against the Delta VOC. Overall, the long-term humoral immune response to SARS-CoV-2 infection in children is of longer duration than in adults even after asymptomatic infection.

Differential uptake of three clinically relevant allergens by human plasmacytoid dendritic cells.

BACKGROUND: Human plasmacytoid dendritic cells (pDC) have a dual role as interferon-producing and antigen-presenting cells. Their relevance for allergic diseases is controversial. and the impact of pDC on allergic immune responses is poorly understood. METHODS: This in vitro study on human pDC isolated from peripheral blood was designed to compare side by side the uptake of three clinically relevant representative allergens: fluorochrome-labeled house dust mite Der p 1, Bee venom extract from Apis mellifera (Api) and the food allergen OVA analyzed flow cytometry and confocal microscopy. RESULTS: We found that the internalization and its regulation by TLR9 ligation was significantly different between allergens in terms of time course and strength of uptake. Api and OVA uptake in pDC of healthy subjects was faster and reached higher levels than Der p 1 uptake. CpG ODN 2006 suppressed OVA uptake and to a lesser extent Der p 1, while Api internalization was not affected. All allergens colocalized with LAMP1 and EEA1, with Api being internalized particularly fast and reaching highest intracellular levels in pDC. Of note, we could not determine any specific differences in antigen uptake in allergic compared with healthy subjects. CONCLUSIONS: To our knowledge this is the first study that directly compares uptake regulation of clinically relevant inhalative, injective and food allergens in pDC. Our findings may help to explain differences in the onset and severity of allergic reactions as well as in the efficiency of AIT.

Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 in Households with Children, Southwest Germany, May-August 2020.

Resolving the role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in households with members from different generations is crucial for containing the current pandemic. We conducted a large-scale, multicenter, cross-sectional seroepidemiologic household transmission study in southwest Germany during May 11-August 1, 2020. We included 1,625 study participants from 405 households that each had ≥1 child and 1 reverse transcription PCR-confirmed SARS-CoV-2-infected index case-patient. The overall secondary attack rate was 31.6% and was significantly higher in exposed adults (37.5%) than in children (24.6%-29.2%; p = <0.015); the rate was also significantly higher when the index case-patient was >60 years of age (72.9%; p = 0.039). Other risk factors for infectiousness of the index case-patient were SARS-CoV-2-seropositivity (odds ratio [OR] 27.8, 95% CI 8.26-93.5), fever (OR 1.93, 95% CI 1.14-3.31), and cough (OR 2.07, 95% CI 1.21-3.53). Secondary infections in household contacts generate a substantial disease burden.

BNT162b2 Vaccination Elicits Strong Serological Immune Responses Against SARS-CoV-2 Including Variants of Concern in Elderly Convalescents.

Elderly residents of long-term care facilities (LTCFs) have long been underrepresented in studies on vaccine efficacy, particularly in light of currently emerging variants of concern (VOCs). In this prospective observational cohort study, we analyzed serological immune responses in 190 individuals before, 3 weeks after 1st and 3 weeks after 2nd vaccination with BNT162b2. Unvaccinated COVID-19-convalescent subjects served as reference. End points comprised serum anti-spike IgG and IgA titers as well as neutralization capacities against unmutated and mutated SARS-CoV-2 receptor binding domains including B.1.1.7, B.1.351 and P.1. We found that antibody titers and neutralization capacities up to 3 weeks after 2nd vaccination with BNT162b2 were significantly higher in COVID-19-convalescent as compared to COVID-19-naive vaccinees. Moreover, pre-vaccination anti-NCP IgG titers, but not age or gender, had a high impact on the strength and kinetics of post-vaccination neutralization capacity development. Most importantly, BNT162b2-induced neutralization capacity was cross-reactive with VOCs. In contrast to unvaccinated convalescents, vaccinated convalescent individuals of all ages acquired strong neutralizing capacities against current VOCs. The present study suggests that COVID-19-convalescent individuals with a broad age range between 18 and 98 years benefit from BNT162b2 vaccination by developing strong and broad neutralizing immune responses against SARS-CoV-2 including current VOCs.

mRNA Vaccines Enhance Neutralizing Immunity against SARS-CoV-2 Variants in Convalescent and ChAdOx1-Primed Subjects.

To identify the most efficient methods of immunological protection against SARS-CoV-2, including the currently most widespread variants of concern (VOCs)-B.1.1.7, B.1.351 and P.1-a simultaneous side-by-side-comparison of available vaccination regimes is required. In this observational cohort study, we compared immunological responses in 144 individuals vaccinated with the mRNA vaccines BNT162b2 or mRNA-1273 and the vector vaccine ChAdOx1-nCoV-19, either alone, in combination, or in the context of COVID-19-convalescence. Unvaccinated COVID-19-convalescent subjects served as a reference. We found that cellular and serological immune responses, including neutralizing capacity against VOCs, were significantly stronger with mRNA vaccines as compared with COVID-19-convalescent individuals or vaccinated individuals receiving the vector vaccine ChAdOx1-nCoV-19. Booster immunizations with mRNA vaccines triggered strong and broadly neutralizing antibody and IFN-γ responses in 100% of vaccinated individuals investigated. This effect was particularly strong in COVID-19-convalescent and ChAdOx1-nCoV-19-primed individuals, who were characterized by comparably moderate cellular and neutralizing antibody responses before mRNA vaccine booster. Heterologous vaccination regimes and convalescent booster regimes using mRNA vaccines may allow enhanced protection against SARS-CoV-2, including current VOCs. Furthermore, such regimes may facilitate rapid (re-)qualification of convalescent plasma donors with high titers of broadly neutralizing antibodies.

Diagnostic accuracy of MRI with MRCP and B-Mode-sonography with elastography of the pancreas in patients with cystic fibrosis: a point-to-point comparison.

OBJECTIVE: For patients with cystic fibrosis, the imaging of the pancreas is of crucial importance for the early detection of pancreatic carcinoma. Comparative studies between Magnetic Resonance Imaging (MRI) and sonographic pancreas sonography are not yet available. The aim of the study was to compare MRI, sonography and point-shearwave elastography (pSWE). A total of 19 patients were included (10 male, 9 female; age 29.7 ± 14.3 years) in the study. Ultrasonography with pSWE and contrast enhanced MRI with MRCP were performed. RESULTS: Significant differences between measurements of pancreatic body were registered in MRI with 1.4 ± 0.6 cm vs 1.0 ± 0.4 cm in ultrasound (p = 0.049), however not for pancreatic head and tail. In 10/19 patients (52.6%) pancreatic parenchyma did not show in MRI because of complete lipomatous transformation, but could be detected in ultrasound. pSWE-values showed no significant differences between the full and partial fatty transformation in pancreatic head (p = 0.968), body (p = 0.657) and tail (p = 0.840). pSWE-values did not correlate with measured signal intensity in T1w flash (p = 0.930, r = 0.025) and T2w HASTE sequences (p = 0.152, r = - 0.375). In patients with CF ultrasound is superior to MRI for displaying full fibro-fatty parenchymal transformation, pancreatic duct. Ultrasound elastography did not provide additional clinical relevant information.

Point shear wave elastography of the pancreas in patients with cystic fibrosis: a comparison with healthy controls.

PURPOSE: Manifestations of cystic fibrosis in the pancreas are gaining in clinical importance as patients live longer. Conventional ultrasonography and point shear wave elastography (pSWE) imaging are non-invasive and readily available diagnostic methods that are easy to perform. The aim of this study was to perform conventional ultrasonography and obtain pSWE values in the pancreases of patients with cystic fibrosis and to compare the findings with those of healthy controls. METHODS: 27 patients with cystic fibrosis (13 women/14 men; mean age 27.7 ± 13.7 years; range 9-58 years) and 60 healthy control subjects (30 women/30 men; mean age 30.3 ± 10.0 years; range 22-55 years) underwent examinations of the pancreas with conventional ultrasound and pSWE imaging. RESULTS: Patients with cystic fibrosis have an echogenic pancreatic parenchyma. We found cystic lesions of the pancreas in six patients. pSWE imaging of the pancreatic parenchyma gave significantly lower shear wave velocities in patients with cystic fibrosis than in the control group (1.01 m/s vs 1.30 m/s; p < 0.001). CONCLUSIONS: Using pSWE imaging in vivo, we have shown that the pancreas is considerably softer in patients with cystic fibrosis than in a healthy control population.