Cell-based influenza vaccines: An effective vaccine option for under 60-year-olds.

Aim: Seasonal influenza poses a significant burden of disease, affecting not only older adults but also individuals under the age of 60. It carries a high economic burden, mainly driven by influenza-associated productivity losses in the working population. Conventional egg-based influenza vaccines may have reduced effectiveness due to antigen adaptation in eggs. In contrast, cell-based influenza vaccines are less likely to be affected by such antigen adaptation. This review aims to present real-world data (RWD) comparing the effectiveness of quadrivalent cell-based (QIVc) and egg-based (QIVe) influenza vaccines over three consecutive seasons. Methods: A comprehensive review was conducted, analyzing RWD from retrospective cohort and case-control studies on the relative vaccine effectiveness (rVE) of QIVc versus QIVe during the 2017/18-2019/20 seasons. Results: This study included six retrospective cohort studies and one case-control study, with a combined total of approximately 29 million participants. A cohort study involving people aged ≥4 years during the 2017/18 season showed a statistically significant rVE of QIVc compared to QIVe in preventing influenza-like illness, with a value of 36.2%. QIVc demonstrated statistically significant superiority over QIVe in preventing outpatient and inpatient medical encounters as observed in two cohort studies conducted during the 2018/19 and 2019/20 seasons. The rVE of QIVc compared to QIVe was found to be 7.6% in individuals aged ≥4 years and 9.5% in individuals aged ≥18 years. Three additional cohort studies conducted between 2017/18-2019/20 reported a statistically significant improvement in rVE (5.3-14.4%) of QIVc compared to QIVe in preventing influenza-related hospitalizations and emergency department visits due to influenza in individuals aged 4-64 years. In a case-control study across all three seasons, QIVc showed statistically significantly higher effectiveness compared to QIVe in preventing test-confirmed influenza, with rVEs of 10.0-14.8%. Conclusions: RWD from the 2017/18-2019/20 seasons demonstrated that QIVc is more effective than QIVe in preventing influenza-related outcomes in individuals aged 4-64 years. Preferential use of cell-based influenza vaccines, as opposed to conventional egg-based vaccines, could reduce the burden of influenza-related symptoms on individuals and alleviate the economic impact on the German population under 60 years of age.

SARS-CoV-2-specific cellular and humoral immunity after bivalent BA.4/5 COVID-19-vaccination in previously infected and non-infected individuals.

Knowledge is limited as to how prior SARS-CoV-2 infection influences cellular and humoral immunity after booster-vaccination with bivalent BA.4/5-adapted mRNA-vaccines, and whether vaccine-induced immunity may indicate subsequent infection. In this observational study, individuals with prior infection (n = 64) showed higher vaccine-induced anti-spike IgG-antibodies and neutralizing titers, but the relative increase was significantly higher in non-infected individuals (n = 63). In general, both groups showed higher neutralizing activity towards the parental strain than towards Omicron-subvariants BA.1, BA.2 and BA.5. In contrast, CD4 or CD8 T cell levels towards spike from the parental strain and the Omicron-subvariants, and cytokine expression profiles were similar irrespective of prior infection. Breakthrough infections occurred more frequently among previously non-infected individuals, who had significantly lower vaccine-induced spike-specific neutralizing activity and CD4 T cell levels. In summary, we show that immunogenicity after BA.4/5-bivalent vaccination differs between individuals with and without prior infection. Moreover, our results may help to improve prediction of breakthrough infections.

[Cell-based influenza vaccines: an effective vaccine option for under 60-year-olds]. / Zellkulturbasierte Influenzaimpfstoffe: eine effektive Impfstoffoption für unter 60-Jährige.

The population < 60 years of age is also affected by a significant disease burden from seasonal influenza. It carries a high economic burden, mainly driven by influenza-associated productivity losses in the working population. Conventional egg-based influenza vaccines may experience reduced effectiveness due to antigen adaptation in eggs. In contrast, cell-based influenza vaccines are less likely to be affected by antigenic adaptations to the host system and showed better effectiveness in individuals 4-64 years old over several seasons compared to conventional egg-based influenza vaccines under real-world conditions. Preferential use of cell-based influenza vaccines, as opposed to conventional egg-based vaccines, could reduce the burden of influenza-related symptoms on individuals and alleviate the economic impact on the German population < 60 years of age.

Dental aerosol-producing treatments: Comparison of contamination patterns of face shields and surgical masks.

During the COVID-19 pandemic, dental face shields were recommended to protect the eyes. This study aimed to examine to what extent face shield and mask contamination differ when a pre-procedural mouth rinsing with Chlorhexidine (CHX) is conducted before treatment. In this prospective, randomized study, three groups of subjects were formed (rinsing with 0.1% CHX, water, or no rinsing (control) before aerosol-producing treatments). After each of the 301 treatments, the practitioner's face shield was swabbed with eSwab and the mask was brought into contact with agar plates. Sampling was done from the exterior surface only. Samples were cultured for 48 h at 35 °C under aerobic and anaerobic conditions. Bacteria were classified by phenotypic characteristics, biochemical test methods, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Colony-forming units were counted and mean values were compared (WSR, H-test, U-test, p < 0.05). Within each subject group, face shields showed significantly more contamination than surgical masks (control group: 350 CFU, 50 CFU; intervention water: 270 CFU, 40 CFU; intervention CHX: 250 CFU, 30 CFU). Comparison of face shields of the different subject groups did not reveal any statistically significant differences. However, CHX resulted in a statistically significant bacterial reduction on surgical masks compared to the water and control group (control: 50 CFU, intervention water: 40 CFU, intervention CHX: 30 CFU). Contamination of face shields and surgical masks was highest in the control group, followed by the water group, and lowest in the intervention group with CHX. Streptococcus spp. and Staphylococcus spp. dominated, representing the oral and cutaneous flora. Contamination of masks worn with or without face shields did not differ. Presumably, face shields intercept first splashes and droplets, while the masks were mainly exposed to bioaerosol mist. Consequently, face shields protect the facial region and surroundings from splashes and droplets, but not the mask itself. A pre-procedural mouth rinse with CHX had no statistically significant reducing effect on contamination of the face shield, but a statistically significant reducing effect was observed on contamination of the mask.

Detection of viable oral bacteria of the patient on the surgical mask of dentists.

INTRODUCTION AND AIM: Bioaerosols contaminate the personal protective equipment (PPE), especially masks. The PPE harbors microorganisms from various sources. However, no previous studies have investigated the specific sources of bacteria found on used masks and their correlation with those from the treated patient. SETTING, DESIGN, MATERIAL AND METHODS: Intraoral samples from the patient were collected prior to dental aerosol-producing treatments using a nylon flock fiber swab. After treatment, the practitioner's mask was imprinted onto agar plates. MAIN OUTCOME METHODS: Following cultivation, colony forming units were counted and identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). After the samples were analyzed, the intraoral samples as well as the mask samples were assessed for the presence of identical species, which were subsequently quantified. RESULTS: 126 treatments were included. One species match occurred most frequently (26.2%), followed by two (11.9%%) and three or more (3.97%). In the intraoral samples, Neisseria subflava occurred most often, within mask samples Staphylococcus epidermidis were detected most. Staphylococcus aureus could be cultivated three times more often in intraoral samples than on the mask. DISCUSSION AND CONCLUSION: Oral microorganisms originating from the patient's oral cavity can be found on the outside of masks. When using PPE during treatments, it should therefore always be in mind that potentially pathogenic microorganisms may land on the mask becoming a source of for itself.

Bacterial contamination potential of personal protective equipment itself in dental aerosol-producing treatments.

Personal protective equipment (PPE) has long been a high priority in dental aerosol-producing treatments. Since COVID-19 pandemic, its importance has increased yet again. While importance of PPE in preventing transmission and thus possible infection of pathogens is well known, contamination potential of PPE after treatment itself is less investigated. This review aims to give an overview of the current literature and contamination potential (viral, blood, bacterial) of components of protective equipment itself. The literature search was performed using the Medline database; furthermore, a hand search was conducted. Last search took place on 23 November 2022. Two categories of hygiene-related keywords were formed (category A: mask, face shield, goggles, eyewear, personal protective equipment; category B: contamination, aerosol). Each keyword from one category was combined with all keywords from the other one. In addition, the keyword "dental" was always added. First, a title and abstract screening was performed. Afterward, a full-text analysis was followed for the included studies. A total of 648 search hits were found in the Medline database. 47 were included after title and abstract screening. 22 studies were excluded after full-text analysis, 25 studies were included. The hand search resulted in 4 studies that were included. Bacterial contamination of PPE after treatment has been adequately studied, contamination with blood less. Microorganisms mainly originate from the oral and cutaneous flora; however, a transmission of potential pathogens like Staphylococcus aureus or Escherichia coli was also described. Studies showing transmission pathways starting from PPE and its various components are lacking. No measures have yet been described that fully protect the protective equipment from contamination. There is growing awareness that PPE itself can be a source of pathogen transmission, and thus possible infection. Therefore, not only wearing of protective clothing, but also conscious handling of it is crucial for transmission and possible infection prevention. However, studies showing transmission pathways starting from PPE and its various components are lacking. Several studies have investigated what measures can be taken to protect the protective equipment itself. So far, none of the methods evaluated can prevent contamination of PPE.

Real world evidence for public health decision-making on vaccination policies: perspectives from an expert roundtable.

INTRODUCTION: Influenza causes significant morbidity and mortality, but influenza vaccine uptake remains below most countries' targets. Vaccine policy recommendations vary, as do procedures for reviewing and appraising the evidence. AREAS COVERED: During a series of roundtable discussions, we reviewed procedures and methodologies used by health ministries in four European countries to inform vaccine recommendations. We review the type of evidence currently recommended by each health ministry and the range of approaches toward considering randomized controlled trials (RCTs) and real-world evidence (RWE) studies when setting influenza vaccine recommendations. EXPERT OPINION: Influenza vaccine recommendations should be based on data from both RCTs and RWE studies of efficacy, effectiveness, and safety. Such data should be considered alongside health-economic, cost-effectiveness, and budgetary factors. Although RCT data are more robust and less prone to bias, well-designed RWE studies permit timely evaluation of vaccine benefits, effectiveness comparisons over multiple seasons in large populations, and detection of rare adverse events, under real-world conditions. Given the variability of vaccine effectiveness due to influenza virus mutations and increasing diversification of influenza vaccines, we argue that consideration of both RWE and RCT evidence is the best approach to more nuanced and timely updates of influenza vaccine recommendations.

Attitudes of primary care physicians towards antimicrobial stewardship and the impact of a multi-part training course - a pilot study.

Background: A plethora of antimicrobial stewardship (AMS) programs has been initiated during the past years, focusing on hospital settings. Primary-care physicians have seldom been addressed, although the majority of antibiotic prescriptions are issued for outpatients. We sought to investigate attitudes of primary-care physicians and the impact of a customized training course. Methods: Primary-care physicians in southwest Germany were invited to a multi-part training course on AMS in the primary-care setting. Participants were asked to answer a questionnaire about their attitude and factors that hinder them from implementing AMS or enable them to perform AMS. In addition, a knowledge assessment exam at the beginning and end of the training was conducted on selected infectious diseases/syndromes. Results: In total, 36 primary-care physicians participated in the training course. The predominant age group was 51-60 years old (36%; 13/36). The majority, 23/35 (66%), indicated never having had AMS training, while 22/35 (63%) acknowledged partly implementing AMS activities in their daily routine. The primary barrier was lack of expertise, while the main motives were reducing antimicrobial resistance and optimizing patient care. The provision of guidelines was regarded as more important than feedback on their prescription behavior. Exam performance improved from the initial to the final exam on all topics. Conclusion: Customized AMS training courses are a feasible and potentially complimentary tool to address antibiotic misuse in the primary-care setting.

Alterations in pathogen-specific cellular and humoral immunity associated with acute peripheral facial palsy of infectious origin.

BACKGROUND: Peripheral facial palsy (PFP) is a common neurologic symptom which can be triggered by pathogens, autoimmunity, trauma, tumors, cholesteatoma or further local conditions disturbing the peripheral section of the nerve. In general, its cause is often difficult to identify, remaining unknown in over two thirds of cases. As we have previously shown that the quantity and quality of pathogen-specific T cells change during active infections, we hypothesized that such changes may also help to identify the causative pathogen in PFPs of unknown origin. METHODS: In this observational study, pathogen-specific T cells were quantified in blood samples of 55 patients with PFP and 23 healthy controls after stimulation with antigens from varicella-zoster virus (VZV), herpes-simplex viruses (HSV) or borrelia. T cells were further characterized by expression of the inhibitory surface molecule CTLA-4, as well as markers for differentiation (CD27) and proliferation (Ki67). Pathogen-specific antibody responses were analyzed using ELISA. Results were compared with conventional diagnostics. RESULTS: Patients with PFP were more often HSV-seropositive than controls (p = 0.0003), whereas VZV- and borrelia-specific antibodies did not differ between groups. Although the quantity and general phenotypical characteristics of antigen-specific T cells did not differ either, expression of CTLA-4 and Ki67 was highly increased in VZV-specific T cells of 9 PFP patients, of which 5 showed typical signs of cutaneous zoster. In the remaining 4 patients, a causal relationship with VZV was possible but remained unclear by clinical standard diagnostics. A similar CTLA-4- and Ki67-expression profile of borrelia-specific T cells was also found in a patient with acute neuroborreliosis. DISCUSSION: In conclusion, the high prevalence of HSV-seropositivity among PFP-patients may indicate an underestimation of HSV-involvement in PFP, even though HSV-specific T cell characteristics seem insufficient to identify HSV as a causative agent. In contrast, striking alterations in VZV- and borrelia-specific T cell phenotype and function may allow identification of VZV- and borrelia-triggered PFPs. If confirmed in larger studies, antigen-specific immune-phenotyping may have the potential to improve specificity of the clinical diagnosis.

Discrimination between hypervirulent and non-hypervirulent ribotypes of Clostridioides difficile by MALDI-TOF mass spectrometry and machine learning.

Hypervirulent ribotypes (HVRTs) of Clostridioides difficile such as ribotype (RT) 027 are epidemiologically important. This study evaluated whether MALDI-TOF can distinguish between strains of HVRTs and non-HVRTs commonly found in Europe. Obtained spectra of clinical C. difficile isolates (training set, 157 isolates) covering epidemiologically relevant HVRTs and non-HVRTs found in Europe were used as an input for different machine learning (ML) models. Another 83 isolates were used as a validation set. Direct comparison of MALDI-TOF spectra obtained from HVRTs and non-HVRTs did not allow to discriminate between these two groups, while using these spectra with certain ML models could differentiate HVRTs from non-HVRTs with an accuracy >95% and allowed for a sub-clustering of three HVRT subgroups (RT027/RT176, RT023, RT045/078/126/127). MALDI-TOF combined with ML represents a reliable tool for rapid identification of major European HVRTs.

Differences in SARS-CoV-2 specific humoral and cellular immune responses after contralateral and ipsilateral COVID-19 vaccination.

BACKGROUND: Individual doses of dual-dose vaccine-regimens are sequentially administered into the deltoid muscle, but little attention has so far been paid to the immunological effects of choosing the ipsilateral or the contralateral side for the second dose. METHODS: In an observational study, 303 previously naive individuals were recruited, who received the second dose of the COVID-19 vaccine BNT162b2 on either the ipsilateral (n = 147) or the contralateral side (n = 156). Spike-specific IgG, IgG-avidity, and neutralizing antibodies were quantified using ELISA and a surrogate assay 2 weeks after dose 2. A subgroup of 143 individuals (64 ipsilateral, 79 contralateral) was analysed for spike-specific CD4 and CD8 T-cells using flow-cytometry. FINDINGS: Median spike-specific IgG-levels did not differ after ipsilateral (4590 (IQR 3438) BAU/ml) or contralateral vaccination (4002 (IQR 3524) BAU/ml, p = 0.106). IgG-avidity was also similar (p = 0.056). However, neutralizing activity was significantly lower after contralateral vaccination (p = 0.024). Likewise, median spike-specific CD8 T-cell levels were significantly lower (p = 0.004). Consequently, the percentage of individuals with detectable CD8 T-cells was significantly lower after contralateral than after ipsilateral vaccination (43.0% versus 67.2%, p = 0.004). Spike specific CD4 T-cell levels were similar in both groups, but showed significantly higher CTLA-4 expression after contralateral vaccination (p = 0.011). These effects were vaccine-specific, as polyclonally stimulated T-cell levels did not differ. INTERPRETATION: Both ipsilateral and contralateral vaccination induce a strong immune response, but secondary boosting is more pronounced when choosing vaccine administration-routes that allows for drainage by the same lymph nodes used for priming. Higher neutralizing antibody activity and higher levels of spike-specific CD8 T-cells may have implications for protection from infection and severe disease and support general preference for ipsilateral vaccination. FUNDING: Financial support was provided in part by the State chancellery of the Saarland to M.S.

[Measures and Recommendations for Ensuring Adequate Inpatient Care Capacities for Pandemic Management within a Region: Results of a Hybrid Delphi Method]. / Maßnahmen und Empfehlungen für die Sicherstellung adäquater stationärer Versorgungskapazitäten für das Pandemiemanagement innerhalb einer Region ­ Ergebnisse eines hybriden Delphi-Verfahrens.

INTRODUCTION: Since the beginning of the pandemic in spring 2020, inpatient healthcare has been under enormous burden, which is reflected especially in overworked staff, imprecise bed planning and/or data transfer. According to the recommendation of the Science Council, university clinics should play a controlling role in regional healthcare and act in conjunction with surrounding hospitals and practices. METHODS: In September 2021, 31 representatives from 18 university hospitals were invited to a hybrid Delphi study with a total of 4 survey rounds to discuss criteria for effective inpatient care in a pandemic situation, which were extracted from previous expert interviews. Criteria that were classified as very important/relevant by≥75% of the participants in the first round of the survey (consensus definition) were then further summarized in 4 different small groups. In a third Delphi round, all participants came together again to discuss the results of the small group discussions. Subsequently, these were prioritized as Optional ("can"), Desirable ("should") or Necessary ("must") recommendations. RESULTS: Of the invited clinical experts, 21 (67.7%) participated in at least one Delphi round. In an online survey (1st Delphi round), 233 criteria were agreed upon and reduced to 84 criteria for future pandemic management in four thematic small group discussions (2nd Delphi round) and divided into the small groups as follows: "Crisis Management and Crisis Plans" (n=20), "Human Resources Management and Internal Communication" (n=16), "Regional Integration and External Communication" (n=24) and "Capacity Management and Case & Care" (n=24). In the following group discussion (3rd Delphi round), the criteria were further modified and agreed upon by the experts, so that in the end result, there were 23 essential requirements and recommendations for effective inpatient care in a pandemic situation. CONCLUSION: The results draw attention to key demands of clinical representatives, for example, comprehensive digitization, standardization of processes and better (supra) regional networking in order to be able to guarantee needs-based care even under pandemic conditions. The present consensus recommendations can serve as guidelines for future pandemic management in the inpatient care sector.

Factors Associated With SARS-CoV-2 Infection at a German Medical Congress During the Omicron Wave.

This cross-sectional study assesses factors associated with SARS-CoV-2 infection rates at the 122nd Annual Congress of the German Society of Ophthalmology in 2022, which was held in-person for the first time in 3 years, during the Omicron wave.

Occurrence, resistance patterns, and management of carbapenemase-producing bacteria in war-wounded refugees from Ukraine.

We analyzed consecutive clinical cases of infections due to carbapenemase-producing gram-negative bacteria detected in war-wounded patients from Ukraine who were treated at one university medical center in southwest Germany between June and December 2022. The isolates of multiresistant gram-negative bacteria were subjected to a thorough microbiological characterization and whole genome sequencing (WGS). We identified five war-wounded Ukrainian patients who developed infections with New Delhi metallo-ß-lactamase 1-positive Klebsiella pneumoniae. Two isolates also carried OXA-48 carbapenemases. The bacteria were resistant to novel antibiotics, such as ceftazidime/avibactam and cefiderocol. The used treatment strategies included combinations of ceftazidime/avibactam + aztreonam, colistin, or tigecycline. WGS suggested transmission during primary care in Ukraine. We conclude that there is an urgent need for thorough surveillance of multiresistant pathogens in patients from war zones.

Transient Positive SARS-CoV-2 PCR without Induction of Systemic Immune Responses.

SARS-CoV-2 testing is dominated by PCR to guide treatment and individual as well as public health preventive measures. Among 1700 football (soccer) players and staff of the German Bundesliga and Bundesliga 2 who were regularly tested by PCR twice weekly, 98 individuals had a positive PCR (May 2020 to mid-January 2021). A subset of these were retested shortly after the initial positive result. Among those, 11 subjects were identified who only had a transient single positive PCR of low viral load. All individuals were asymptomatic and none developed long COVID. We tested SARS-CoV-2 IgG and IgA as well as SARS-CoV-2 specific CD4 und CD8 positive T cells, and showed that only one out of 11 individuals developed SARS-CoV-2 specific cellular and humoral immunity after the positive PCR, whereas a specific immunity was undetectable in all other individuals. Thus, a single positive PCR might indicate that transient colonization of the upper respiratory tract with SARS-CoV-2 may occur without systemic induction of specific adaptive immunity. Together with test artifacts as another potential reason for a transiently positive test, this finding may favor cautious interpretation of positive PCR results or retesting before initiating intervening treatment or infection control measures in some cases.

[Outpatient Antibiotic Prescription Rates and Mastoiditis in Children and Adolescents, Saarland, 2014-2019]. / Ambulante Antibiotika-Verordnungsrate und Mastoiditis-Fälle bei Kindern und Jugendlichen im Saarland, 2014­2019.

BACKGROUND: Infections of the respiratory tract are the main indication for outpatient antibiotic therapy in children and adolescents. In recent years the antibiotic prescription rate (APR) in the pediatric population has decreased significantly. OBJECTIVES: The aim of the retrospective mastoiditis audit in the PaedineSaar network is to investigate the incidence of inpatient acute mastoiditis (AM) in Saarland (2014-2019) regarding to the decreasing APRs in children, as well as to gather data of the clinical course of AM. METHODS: All inpatient AM cases 2014-2019 were analyzed retrospectively from 6 hospitals for pediatrics and/or otorhinolaryngology in Saarland and Trier. Children and adolescents aged 0-17 years and residing in Saarland were included in the study. RESULTS: 2014-2019 53 inpatient treated AM cases have been recorded. During the study period there was no significant increase of AM incidence (mean incidence 2014-2019: 6.1/100,000). 34% (18/53) of the patients received prehospital antibiotic treatment (main indication: acute otitis media (AOM) 15/18, 83%). At least one complication occurred in 30% of the patients (16/53). There was a slight trend to more complications in children without oral antibiotic treatment before admission (14/35 (40%) vs. 2/18 (11%) p=0.056). CONCLUSIONS: The incidence of AM leading to inpatient treatment in children in Saarland did not increase 2014-2019 despite a significant and sustained decline in the outpatient APRs. The results of this audit should be used for the development of a more standardized approach concerning the diagnostics and treatment of children with AM.

Contact times in professional football before and during the SARS-CoV-2 pandemic: Tracking data from the German Bundesliga.

The global SARS-CoV-2 pandemic led to a lockdown in team sports in March 2020. Because the risk of virus transmission seems to correlate with the duration of close contacts, data on contact times are necessary to assess the risk of virus transmission in sports. In this study, an optical tracking system was used to determine contact times between players of the two highest men's professional football leagues in Germany in the 2019-20 season and in the first half of the 2020-21 season. Contacts between players were defined as being within a two-metre radius during matches and were differentiated as either match-specific or non-match-specific. In total, 918 matches with 197,087 contacts were analysed. The mean overall contact time of one-to-one situations of 36 s (SD: ± 66) before the lockdown was reduced to 30 s after the lockdown (SD: ± 60) (p < 0.0001). In professional football, contacts between two players infrequently occur within a two-metre radius, averaging less than 35 s. Only 36 player pair contacts lasted for more than 15 min (0.00018%). The mean accumulated contact time per player with all others was 10.6 ± 6.9 min per match, with a decrease from 11.6 ± 7.0 min before the lockdown to 10.0 ± 6.6 min (p < 0.0001) after lockdown in the season 2019-20. The SARS-CoV-2 pandemic has resulted in a reduction in match-specific contacts of 25%. It seems questionable if such short contacts in open-air sports may lead to considerable virus transmission.

Microbiological Surveillance of Heater-Cooler Units Used in Cardiothoracic Surgery for Detection of Mycobacterium chimaera.

Mycobacterium chimaera is a nontuberculous mycobacterium that was identified as causative agent in a global outbreak of severe infections following open-chest cardiothoracic surgery. Heater-cooler units (HCUs), which were contaminated during the manufacturing process, were elucidated as the origin of this outbreak. Regular surveillance of water-containing HCUs used for cardiac surgery was recommended as one preventive measure. We present data on the occurrence of M. chimaera and other mycobacterial pathogens in different HCUs from one surgical center in Germany over a 42-month period. Water samples and swabs from seven different HCUs were taken between 2015 and 2018, and mycobacteria were detected in 50.6% (78/154) of water samples and 21.1% (4/19) of swabs. M. chimaera accounted for the majority of detected pathogens (77/83 isolates in water samples), but other species such as Mycobacterium gordonae were also found. Despite strict adherence to an intensified, regular disinfection procedure, the majority of HCUs remained positive for mycobacteria until the end of the study. In conclusion, additional measures are needed to reduce the risk of intraoperative transmission of M. chimaera, and our observations underscore the inherent infections risks associated with water-containing medical devices.

Comparative immunogenicity and reactogenicity of heterologous ChAdOx1-nCoV-19-priming and BNT162b2 or mRNA-1273-boosting with homologous COVID-19 vaccine regimens.

Comparative analyses of the immunogenicity and reactogenicity of homologous and heterologous SARS-CoV-2 vaccine-regimens will inform optimized vaccine strategies. Here we analyze the humoral and cellular immune response following heterologous and homologous vaccination strategies in a convenience cohort of 331 healthy individuals. All regimens induce immunity to the vaccine antigen. Immunity after vaccination with ChAdOx1-nCoV-19 followed by either BNT162b2 (n = 66) or mRNA-1273 (n = 101) is equivalent to or more pronounced than homologous mRNA-regimens (n = 43 BNT162b2, n = 59 mRNA-1273) or homologous ChAdOx1-nCoV-19 vaccination (n = 62). We note highest levels of spike-specific CD8 T-cells following both heterologous regimens. Among mRNA-containing combinations, spike-specific CD4 T-cell levels in regimens including mRNA-1273 are higher than respective combinations with BNT162b2. Polyfunctional T-cell levels are highest in regimens based on ChAdOx1-nCoV-19-priming. All five regimens are well tolerated with most pronounced reactogenicity upon ChAdOx1-nCoV-19-priming, and ChAdOx1-nCoV-19/mRNA-1273-boosting. In conclusion, we present comparative analyses of immunogenicity and reactogenicity for heterologous vector/mRNA-boosting and homologous mRNA-regimens.