[Evaluation of Characteristics and Management of Influenza Patients in Relation to the STIKO Vaccination Recommendation During the 2017/2018 Season]. / Evaluation von Charakteristika und Management von Influenzapatienten in Bezug auf die STIKO Impfempfehlung während der Saison 2017/2018.

BACKGROUND: Every year a large number of patients is suffering from influenza infection with often severe outcome. The influenza season 2017/2018 was characterized by a high number of cases (in Germany>346,000 laboratory-confirmed cases), but also by a high rate of hospitalizations with sometimes severe clinical outcome - also in the group of patients under 60 years. AIM: The aim of the present study was to find out whether patients not fullfilling the STIKO vaccination recommendation in the 2017/18 season were suffering from a worse outcome. MATERIALS AND METHODS: All laboratory-confirmed influenza patients at Frankfurt University Hospital were retrospectively analyzed for disease severity with respect to the primary endpoint. Secondary endpoints were defined as demographic data, length of hospital stay, previous illnesses, intensive care therapy and its duration, drug therapy, and mortality. RESULTS: Fifty-one of 303 patients (16.8%) required intensive care treatments. Of these 51, 46 patients (90.2%) belonged to the group that should have been vaccinated according to the vaccination recommendations according to STIKO, 5 patients (9.8%) did not belong to this group (p=0.434). Of the 51 ICU patients, 16 (31.4%) died. All deceased were from the group with vaccination recommendation (p=0.120). CONCLUSIONS: Based on these data, it appears that severe disease progression occurs in both the group of patients with and without STIKO vaccination recommendation, but deaths occur only in the group of patients with recommendation.

[Occupationally acquired SARS-CoV-2 infections among healthcare personnel in Frankfurt am Main from March to August 2020]. / Beruflich erworbene SARS-CoV-2-Infektionen bei medizinischem Personal in Frankfurt am Main von März bis August 2020.

BACKGROUND: Standardised surveillance of COVID-19 infections among healthcare personnel during the current pandemic was and is not available. In particular, the proportion of occupational infections among healthcare personnel and which workers among them are most at risk remains unclear. OBJECTIVES: The aim of this study was to analyse the reported COVID-19 cases among healthcare personnel in Frankfurt/Main during the first six months of the pandemic, to determine the number of occupational infections and thus to allow a better interpretation of the data published by the Robert Koch Institute. METHODS: Data from the Frankfurt/Main Health Protection Authority was analysed for the period from 1 March to 31 August 2020, and healthcare personnel were recruited for a cross-sectional survey. Three subgroups were defined and analysed according to whether the infectious contact occurred at work, in private or in an unknown setting. RESULTS: Healthcare personnel accounted for 11.8% (319/2700) of all reported COVID-19 cases in Frankfurt/Main during the period studied. In the survey, 47.2% of respondents reported that their infection was acquired in the workplace. There was an association of contact with COVID-19 patients as well as employment in the internal medicine ward and a reported work-related infection. Also apparent was an association between suspected occupational infections and consequently filed reports for alleged occupational disease. DISCUSSION AND CONCLUSION: Health protection authorities are in a position to collect relevant data on work-related transmissions in healthcare occupations and workplaces and should generate standardised data on infected healthcare personnel. This data is necessary to take targeted infection control and prevention measures that protect healthcare personnel and their patients.

Typical symptoms of common otorhinolaryngological diseases may mask a SARS-CoV-2 infection.

PURPOSE: Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) replicates predominantly in the upper respiratory tract and is primarily transmitted by droplets and aerosols. Taking the medical history for typical COVID-19 symptoms and PCR-based SARS-CoV-2 testing have become established as screening procedures. The aim of this work was to describe the clinical appearance of SARS-CoV-2-PCR positive patients and to determine the SARS-CoV-2 contact risk for health care workers (HCW). METHODS: The retrospective study included n = 2283 SARS-CoV-2 PCR tests from n = 1725 patients with otorhinolaryngological (ORL) diseases performed from March to November 2020 prior to inpatient treatment. In addition, demographic data and medical history were assessed. RESULTS: n = 13 PCR tests (0.6%) were positive for SARS-CoV-2 RNA. The positive rate showed a significant increase during the observation period (p < 0.01). None of the patients had clinical symptoms that led to a suspected diagnosis of COVID-19 before PCR testing. The patients were either asymptomatic (n = 4) or had symptoms that were interpreted as symptoms typical of the ORL disease or secondary diagnoses (n = 9). CONCLUSION: The identification of SARS-CoV-2-positive patients is a considerable challenge in clinical practice. Our findings illustrate that taking a medical history alone is of limited value and cannot replace molecular SARS-CoV-2 testing, especially for patients with ORL diseases. Our data also demonstrate that there is a high probability of contact with SARS-CoV-2-positive patients in everyday clinical practice, so that the use of personal protective equipment, even in apparently "routine cases", is highly recommended.

[COVID-19 with respect to occupational healthcare and public health services]. / COVID-19 im Hinblick auf Arbeitsmedizin und Öffentlichen Gesundheitsdienst.

BACKGROUND: Healthcare personnel (HCP) have an occupation-related risk of an infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and can transmit COVID-19 to patients. The related occupational disease is the BK 3101. OBJECTIVE: The frequency of suspected claims of occupation-related SARS-CoV­2 infections and confirmed claims of COVID-19 occupational diseases, reporting obligations under the German Infection Protection Act (IfSG) and mandatory notification requirements of physicians. MATERIAL AND METHODS: Selective literature search with special respect to data of accident insurance institutions regarding occupation-related SARS-CoV­2 infections among HCP. RESULTS: The SARS-CoV­2 pandemic also represents a challenge for occupational healthcare and the public health service. In recent months an increased number of suspected cases of an occupational disease (BK 3101) associated with COVID-19 were registered at the accident insurance institutions as well as notifications of accidents at work. The public health service handles registrations under the IfSG and coordinates the tracking of contact persons. CONCLUSION: Occupation-related SARS-CoV­2 infections are a real reason for concern. The registration data of the accident insurance institutions confirm high case numbers. Preventive measures, such as wearing personal protective equipment (PPE) and COVID-19 vaccinations significantly reduce the risk of infection among HCP as well as the risk of nosocomial transmission to patients.

High Glucosylceramides and Low Anandamide Contribute to Sensory Loss and Pain in Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) causes chronic pain in two-thirds of patients, in part originating from sensory neuropathies. The aim of the present study was to describe the phenotype of PD-associated sensory neuropathy and to evaluate its associations with lipid allostasis, the latter motivated by recent genetic studies associating mutations of glucocerebrosidase with PD onset and severity. Glucocerebrosidase catalyzes the metabolism of glucosylceramides. METHODS: We used quantitative sensory tests, pain ratings, and questionnaires and analyzed plasma levels of multiple bioactive lipid species using targeted lipidomic analyses. The study comprised 2 sets of patients and healthy controls: the first 128 Israeli PD patients and 224 young German healthy controls for exploration, the second 50/50 German PD patients and matched healthy controls for deeper analyses. RESULTS: The data showed a 70% prevalence of PD pain and sensory neuropathies with a predominant phenotype of thermal sensory loss plus mechanical hypersensitivity. Multivariate analyses of lipids revealed major differences between PD patients and healthy controls, mainly originating from glucosylceramides and endocannabinoids. Glucosylceramides were increased, whereas anandamide and lysophosphatidic acid 20:4 were reduced, stronger in patients with ongoing pain and with a linear relationship with pain intensity and sensory losses, particularly for glucosylceramide 18:1 and glucosylceramide 24:1. CONCLUSIONS: Our data suggest that PD-associated sensory neuropathies and PD pain are in part caused by accumulations of glucosylceramides, raising the intriguing possibility of reducing PD pain and sensory loss by glucocerebrosidase substituting or refolding approaches. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Vitamin D in Type 2 Diabetes: Genetic Susceptibility and the Response to Supplementation.

Variants of vitamin D metabolism-genes may predispose to type 2 diabetes (T2D). This study investigated the impact of these variants on disease susceptibility, Vitamin D, parathyroid hormone, C-peptide and HbA1c levels before and after cholecalciferol supplementation in patients with T2D.Twelve polymorphisms within CYP2R1, CYP27B1, DBP, VDR and CYP24A1 were genotyped in 553 T2D patients and 916 controls. In addition 65 patients receiving either cholecalciferol or placebo were analyzed during 6 months intervention and 6 months follow-up.T2D risk alleles are VDR rs7975232 "G" (pc=0.031), rs1544410 "G" (pc=0.027) and CYP2R1 rs10741657 "A" (pc=0.016). Patients with genotypes CYP27B1 rs10877012 "CC" (pc=4x10-5), DBP rs7041 "GG" (pc=0.003), rs4588 "CC" (pc = 3x10-4), CYP24A1 rs2585426 "CG" (pc=0.006) and rs2248137 "CG" (pc=0.001) showed lower 25(OH)D3 and DBP rs4588 "CC" lower 1,25(OH)2D3 levels (pc=0.005). Whereas DBP rs4588 "CC" (pc=0.009), CYP27B1 rs10877012 "AC" (pc=0.059), VDR rs7975323 "AG" (pc=0.033) and rs1544410 "GG" (pc=0.013) are associated with higher 25(OH)D3 levels at 6 months' follow-up. Significant PTH suppression was detected for CYP2R1 "AG" (pc=0.002), DBP rs4588 "CC" (pc<0.001), VDR rs110735810 "CT" (pc<0.001) and CYP24A1 rs2248137 "GG" (pc=0.021).Genetic variants of the vitamin D system predispose to type 2 diabetes and regulate - partially - vitamin D metabolism, concentrations and the vitamin D status. Vitamin D insufficiency is a T2D risk factor. The response to cholecalciferol supplementation can be measured as 25(OH)D3 increment and PTH suppression. This process is regulated by genes of the vitamin D system conferring modest T2D risk.

[Implementation of an operational concept in an ENT clinic in the context of the SARS-CoV-2 pandemic]. / Implementierung eines Betriebskonzeptes in einer HNO-Klinik im Rahmen der SARS-CoV-2-Pandemie.

The SARS-CoV-2 pandemic poses major challenges for the entire medical care system. Especially in university institutions as maximum care providers, a higher exposure to potentially infectious patients or actual COVID-19 patients is to be expected. In a short period of time, an operational concept had to be developed regarding the current hygiene recommendations of the Robert Koch Institute (RKI), the leading medical societies and the internal hospital hygiene plan. Here, patient safety and employee protection are equally important.In cooperation with the Institute for Medical Microbiology and Hospital Hygiene and the occupational medical service, interventions were defined to develop solutions to minimize the COVID-19 transmission risk for examiners and patients despite limited diagnostic and equipment resources. For this purpose, an operational concept was developed, consisting of various individual actions, e. g. the reduction of outpatient treatment to emergencies, life-threatening diseases and urgent aftercare, a double triage of patients and the introduction of treatment teams.The newly developed operational concept was successfully implemented within a few days. After the initial rollout and several "hygiene inspections" only minor improvements to the concept were necessary. All measures were documented in the internal quality handbook and are accessible to all employees. Since the SARS-CoV-2 pandemic is a dynamic process with regular changes in the development and information status, the operational concept is regularly reviewed for validity and adjusted as necessary.

Work-related infections in dentistry: risk perception and preventive measures.

OBJECTIVES: Evaluation of (1) the risk perception of work-related infections in dentistry, (2) the vaccination status, (3) knowledge of the blood-borne pathogens and HIV post-exposure prophylaxis (PEP) as well as (4) use of personal protective equipment (PPE) (gloves, goggles, mask) among the staff and students of the Center of Dentistry and Oral Medicine (ZZMK [Carolinum]) of the Goethe University Frankfurt/Main. MATERIAL AND METHODS: All staff (dentists, dental assistants) and students of the ZZMK with direct contact to patients were asked to anonymously complete a questionnaire. The results of this survey were compared with respect to gender, age and occupational group. RESULTS: Of 178 employees working and 234 students studying at the ZZMK with direct contact to patients, 108 (61%) and 167 (71%) participated (1 person did not reveal his/her status). Thirty-three per cent of the participants assessed the risk of transmission of blood-borne diseases in dental practice as high. Whereas 94% of the participants were fully vaccinated against hepatitis B, only 21% knew their anti-HBs titer. Fifty per cent of students, 13% of dentists and 45% of the assistants did not know the standardised procedure of HIV-PEP. Ninety-four per cent of the study participants always wore protective gloves, 87% always wore a surgical mask and 67% always wore protective goggles. CONCLUSIONS: The fear of HIV is still the largest, followed by hepatitis C. The participants assessed the risk of transmission in spite of all protective measures from the patient to the dentist significantly higher than the transmission from the dentist to the patient. The use of protective measures, especially goggles, requires further optimizing. CLINICAL RELEVANCE: In general, the use of protective measures, especially goggles, requires further optimizing.

Management of Microbiological Samples in a Confirmed Case of Ebola Virus Disease: Constraints and Limitations.

In light of the recent Ebola virus outbreak, it has to be realized that besides medical treatment, precise algorithms for the management of complicating microbial infections are mandatory for Ebola virus disease (EVD) patients. While the necessity of such diagnostics is apparent, practical details are much less clear. Our approach, established during the treatment of an EVD patient at the University Hospital in Frankfurt am Main, Germany, provides a roadmap for reliable and safe on-site microbiological testing.

Medical students' attitude towards influenza vaccination.

BACKGROUND: Influenza vaccination is recommended for all healthcare personnel (HCP) and most institutions offer vaccination for free and on site. However, medical students do not always have such easy access, and the predictors that might guide the motivation of medical students to get vaccinated are largely unknown. METHODS: We conducted a cross-sectional survey study among pre-clinical medical students in a German University hospital to assess the social cognitive predictors of influenza vaccination, as well as reasons for refusal and acceptance of the vaccine. RESULTS: Findings show that pre-clinical medical students have comparable knowledge gaps and negative attitudes towards influenza vaccination that have previously been reported among HCP. Lower injunctive norms and higher feelings of autonomy contribute to no intention to get vaccinated against influenza, while a positive instrumental attitude and higher feelings of autonomy contribute to a high intention to get vaccinated. The variables in the regression model explained 20% of the variance in intention to get vaccinated. CONCLUSIONS: The identified factors should be addressed early in medical education, and hospitals might benefit from a more inclusive vaccination program and accessibility of free vaccines for their medical students.

[Immunity against measles among healthcare personnel at the University Hospital Frankfurt, 2003-2013]. / Immunität gegen Masern beim medizinischen Personal des Universitätsklinikums Frankfurt, 2003-2013.

BACKGROUND: Despite aiming for the elimination of measles by 2015, the current epidemiological situation in Germany shows that there is still insufficient vaccination coverage among the population. During the present pre-elimination period, nosocomial measles are gaining in importance. AIM: The purpose of our study was to determine the immune status of measles among healthcare personnel and medical students at the University Hospital Frankfurt. Moreover, the knowledge of study participants regarding the WHO's goal of the elimination of measles and the general attitude towards vaccination recommendations were investigated. METHODS: A retrospective study of measles seroprevalence was conducted among healthcare personnel and students at the University Hospital Frankfurt with an observation period of 11 years. In spring 2014, medical students were asked to complete an anonymous questionnaire regarding vaccination status, knowledge of measles and acceptance of measles vaccination recommendations. RESULTS: In total, 9,933 serologies were evaluated and 85.7% of the participants had sufficient immunity against measles. Significant changes in immunity to measles over time were not observed. However, a significant difference in the immunity rate of participants born before 1970 and those born after1970 was found. Participants born before 1970 significantly more often showed sufficient immunity against measles compared to those born later (96.4 vs. 83.3 %, p < 0.0001). Almost 20 % of the medical students were not aware of their measles vaccination status and merely 70.7 % indicated that they had received two measles vaccinations. Furthermore, only 45.4 % of the medical students were familiar with the WHO's goal of eliminating measles by 2015; however 95 % could be classified as vaccination-supporters on the basis of the questionnaire. CONCLUSIONS: Overall, the immunity rate of measles determined by serology within the study population did not reach the WHO goal of ≥ 95 %, and this gap was even greater in group of medical students. Despite the medical students' positive attitude towards vaccination guidelines, the awareness in this field awaits improvement.

"I don't see an added value for myself": a qualitative study exploring the social cognitive variables associated with influenza vaccination of Belgian, Dutch and German healthcare personnel.

BACKGROUND: Health Authorities recommend influenza vaccination of healthcare personnel (HCP) to decrease the transmission of influenza to vulnerable patients. Recent studies have almost exclusively used quantitative questionnaires in order to identify determinants of vaccination behaviour. Interviews enable HCP to express freely why they think they are (not) willing to get vaccinated against influenza. METHODS: By means of semi-structured one-on-one interviews with 123 Belgian, Dutch and German HCP, reasons for and against vaccination, experiences with influenza vaccination, intention to get vaccinated and possible barriers, as well as willingness to advice influenza vaccination to patients were investigated. Data were processed with QSR NVivo 8.0 and analysed using a combination of a deductive and a general inductive approach. RESULTS: Across countries, self-protection, patient protection, and protection of family members were reported as most important reasons to get vaccinated against influenza. Reasons to not get vaccinated against influenza were fear of side effects caused by the vaccine, a low risk-perception, the disbelief in the effectiveness of influenza vaccination, organizational barriers, misconceptions, and undefined negative emotions. CONCLUSIONS: The social cognitive variables underlying the decision of HCP to get vaccinated against influenza (or not) seem to be similar in Belgium, Germany, and the Netherlands, even though some differences surfaced. A quantitative investigation of those social cognitive variables is needed in order to determine the importance of the social cognitive variables in explaining the intention to get vaccinated and the importance of the similarities and differences between countries that have been found in this study.

Immune response after a single dose of the 2010/11 trivalent, seasonal influenza vaccine in HIV-1-infected patients and healthy controls.

BACKGROUND: Immune response rates following influenza vaccination are often lower in HIV-infected individuals. Low vitamin D levels were correlated with weak immune response in cancer patients and are known to be lower in HIV-infected patients. METHODS: Diagnostic study to determine immune response against the H1N1v component after a single, intramuscular dose of the 2010/11 seasonal, trivalent influenza vaccine (TIV) in adult HIV-infected and healthy controls scheduled for influenza vaccination (ClinicalTrials.gov Identifier: NCT01017172). Influenza A/H1N1 antibody titers (AB) were determined before and 21 days after vaccination by hemagglutination inhibition assay. RESULTS: Immune response was not different between HIV-infected patients (n = 36) and healthy controls (n = 42) who were previously naïve to the H1N1v component of the TIV. Comparing HIV-infected patients (n = 55) and healthy controls (n = 63) who had received 1 or 2 doses of an AS03 adjuvanted H1N1 vaccine in the previous winter season (2009/10), seroconversion rate and the geometric mean AB titer after TIV of the HIV-infected patients were more than twice as high compared to healthy controls. This difference was mainly driven by the 2-dose schedule for HIV patients in 2009/10. Vitamin D levels were lower in HIV patients but did not correlate with immune response. CONCLUSION: HIV-infected patients who had received 1 or 2 doses of an adjuvanted H1N1 vaccine in the previous year (2009/10) had a significant higher seroconversion rate following TIV as compared to healthy controls, indicating a stronger memory cell response due to the 2-dose schedule.

Heterologous prime-boost immunization with ChAdOx1-S and BNT162b2: reactogenicity and immunogenicity in a prospective cohort study.

OBJECTIVES: Regarding reactogenicity and immunogenicity, heterologous COVID-19 vaccination regimens are considered as an alternative to conventional immunization schemes. METHODS: Individuals receiving either heterologous (ChAdOx1-S [AstraZeneca, Cambridge, UK]/BNT162b2 [Pfizer-BioNTech, Mainz, Germany]; n = 306) or homologous (messenger RNA [mRNA]-1273 [Moderna, Cambridge, Massachusetts, USA]; n = 139) vaccination were asked to participate when receiving their second dose. Reactogenicity was assessed after 1 month, immunogenicity after 1, 3, and/or 6 months, including a third dose, through SARS-CoV-2 antispike immunoglobulin G, surrogate virus neutralization test, and a plaque reduction neutralization test against the Delta (B.1.167.2) and Omicron (B.1.1.529; BA.1) variants of concern. RESULTS: The overall reactogenicity was lower after heterologous vaccination. In both cohorts, SARS-CoV-2 antispike immunoglobulin G concentrations waned over time with the heterologous vaccination demonstrating higher neutralizing activity than homologous mRNA vaccination after 3 months to low neutralizing levels in the Delta plaque reduction neutralization test after 6 months. At this point, 3.2% of the heterologous and 11.4% of the homologous cohort yielded low neutralizing activity against Omicron. After a third dose of an mRNA vaccine, ≥99% of vaccinees demonstrated positive neutralizing activity against Delta. Depending on the vaccination scheme and against Omicron, 60% to 87.5% of vaccinees demonstrated positive neutralizing activity. CONCLUSION: ChAdOx1-S/BNT162b2 vaccination demonstrated an acceptable reactogenicity and immunogenicity profile. A third dose of an mRNA vaccine is necessary to maintain neutralizing activity against SARS-CoV-2. However, variants of concern-adapted versions of the vaccines would be desirable.

Knowledge, attitude and behavior towards vaccinations among nursing- and health care students in Hesse. An observational study.

Objective: Work-related vaccinations are recommended for employees in nursing and health care professions due to their elevated risk of infection because of job-related exposure. These vaccinations prevent work-related infections, protect patients and help to maintain the medical infrastructure. Thorough training and imparting of knowledge about vaccinations and work-related infections are essential pillars of the vaccination decision and thus for achieving a protective immune status. The present study examines the knowledge, attitudes and behavior of nursing- and health care students in Hesse regarding work-related infections and vaccinations. Methods: In spring 2018, seven nursing schools in Hesse took part in an anonymous survey study. A total of 690 surveys from students of various health care professions were included in the study. The content of the survey was based on the recommendations of the Standing Committee on Vaccination (STIKO), a literature review and sample questions from the World Health Organization (WHO) regarding "vaccine hesitancy". Vaccination cards were also evaluated based on the STIKO recommendations concerning standard vaccinations and occupational vaccinations for health care workers. Results: The risk of acquiring a work-related infection was estimated to be quite high over all years of training. Gaps in knowledge were particularly evident in the area of vaccinations. Only three quarter of those surveyed believed that the effectiveness of vaccinations has been proven, and nearly 30% believed that the doses of the drugs used in vaccines were dangerous. Over 80% of the students had never had an influenza vaccination documented in their vaccination card. Conclusions: The knowledge about vaccinations imparted in the course of the education should be expanded. A special course on the subject of vaccinations and the immune system with practical elements could contribute to a better understanding of how vaccinations work and misunderstandings could be eliminated in early stages of the training through the dialog between the students and the teacher in the classroom and the occupational physician as part of preventive occupational health check-ups.

Monitoring influenza vaccination coverage and acceptance among health-care workers in German hospitals - results from three seasons.

Health-care workers are an important vaccination target group, they are more frequently exposed to infectious diseases and can contribute to nosocomial infections. We established a country-wide online monitoring system to estimate influenza vaccine uptake and its determinants among German hospital staff (OKaPII). The online questionnaire included items on vaccination behavior and reasons for and against influenza vaccination. After a pilot phase in 2016, a country-wide roll-out was performed in 2017. Questions on measles (2018) and hepatitis B (2019) vaccination status were added in subsequent years. In 2017, 2018 and 2019 in total 52, 125 and 171 hospitals with 5 808, 17 891 and 27 163 employees participated, respectively. Influenza vaccination coverage in season 2016/17 and 2017/18 was similar (39.5% and 39.3%) while it increased by 12% in 2018/19 (52.3%). Uptake was higher for physicians than for nurses. Self-protection was the most common reason for influenza vaccination. While physicians mainly identified constraints as reasons for being unvaccinated, nurses mainly referred to a lack of vaccine confidence. Of the hospital staff, 87.0% were vaccinated against measles, 6.3% claimed to be protected due to natural infection; 97.7% were vaccinated against hepatitis B. OKaPII shows that influenza vaccination coverage among German hospital staff is low. Occupational group-specific differences should be considered: physicians might benefit from easier access; information campaigns might increase nurses' vaccine confidence. OKaPII serves as a platform to monitor the uptake of influenza and other vaccines; it also contributes to a better understanding of vaccination behavior and planning of targeted interventions.

Powered air-purifying respirators used during the SARS-CoV-2 pandemic significantly reduce speech perception.

BACKGROUND: Due to the coronavirus disease 2019 (COVID-19) pandemic, interventions in the upper airways are considered high-risk procedures for otolaryngologists and their colleagues. The purpose of this study was to evaluate limitations in hearing and communication when using a powered air-purifying respirator (PAPR) system to protect against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) transmission and to assess the benefit of a headset. METHODS: Acoustic properties of the PAPR system were measured using a head and torso simulator. Audiological tests (tone audiometry, Freiburg speech test, Oldenburg sentence test (OLSA)) were performed in normal-hearing subjects (n = 10) to assess hearing with PAPR. The audiological test setup also included simulation of conditions in which the target speaker used either a PAPR, a filtering face piece (FFP) 3 respirator, or a surgical face mask. RESULTS: Audiological measurements revealed that sound insulation by the PAPR headtop and noise, generated by the blower-assisted respiratory protection system, resulted in significantly deteriorated hearing thresholds (4.0 ± 7.2 dB hearing level (HL) vs. 49.2 ± 11.0 dB HL, p < 0.001) and speech recognition scores in quiet (100.0 ± 0.0% vs. 2.5 ± 4.2%, p < 0.001; OLSA: 20.8 ± 1.8 dB vs. 61.0 ± 3.3 dB SPL, p < 0.001) when compared to hearing without PAPR. Hearing with PAPR was significantly improved when the subjects were equipped with an in-ear headset (p < 0.001). Sound attenuation by FFP3 respirators and surgical face masks had no clinically relevant impact on speech perception. CONCLUSIONS: The PAPR system evaluated here can be considered for high-risk procedures in SARS-CoV-2-positive patients, provided that hearing and communication of the surgical team are optimized by the additional use of a headset.

Sapropterin (BH4) Aggravates Autoimmune Encephalomyelitis in Mice.

Depletion of the enzyme cofactor, tetrahydrobiopterin (BH4), in T-cells was shown to prevent their proliferation upon receptor stimulation in models of allergic inflammation in mice, suggesting that BH4 drives autoimmunity. Hence, the clinically available BH4 drug (sapropterin) might increase the risk of autoimmune diseases. The present study assessed the implications for multiple sclerosis (MS) as an exemplary CNS autoimmune disease. Plasma levels of biopterin were persistently low in MS patients and tended to be lower with high Expanded Disability Status Scale (EDSS). Instead, the bypass product, neopterin, was increased. The deregulation suggested that BH4 replenishment might further drive the immune response or beneficially restore the BH4 balances. To answer this question, mice were treated with sapropterin in immunization-evoked autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. Sapropterin-treated mice had higher EAE disease scores associated with higher numbers of T-cells infiltrating the spinal cord, but normal T-cell subpopulations in spleen and blood. Mechanistically, sapropterin treatment was associated with increased plasma levels of long-chain ceramides and low levels of the poly-unsaturated fatty acid, linolenic acid (FA18:3). These lipid changes are known to contribute to disruptions of the blood-brain barrier in EAE mice. Indeed, RNA data analyses revealed upregulations of genes involved in ceramide synthesis in brain endothelial cells of EAE mice (LASS6/CERS6, LASS3/CERS3, UGCG, ELOVL6, and ELOVL4). The results support the view that BH4 fortifies autoimmune CNS disease, mechanistically involving lipid deregulations that are known to contribute to the EAE pathology.