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Antigen rapid diagnostic tests (RDTs) for SARS coronavirus 2 (SARS-CoV-2) are quick, widely available, and inexpensive. Consequently, RDTs have been established as an alternative and additional diagnostic strategy to quantitative reverse transcription polymerase chain reaction (RT-qPCR). However, reliable clinical and large-scale performance data specific to a SARS-CoV-2 virus variant of concern (VOC) are limited, especially for the Omicron VOC. The aim of this study was to compare RDT performance among different VOCs.This single-centre prospective performance assessment compared RDTs from three manufacturers (NADAL, Panbio, MEDsan) with RT-qPCR including deduced standardized viral load from oropharyngeal swabs for detection of SARS-CoV-2 in a clinical point-of-care setting from November 2020 to January 2022.Among 35 479 RDT/RT-qPCR tandems taken from 26 940 individuals, 164 of the 426 SARS-CoV-2 positive samples tested true positive with an RDT corresponding to an RDT sensitivity of 38.50% (95% CI, 34.00-43.20%), with an overall specificity of 99.67% (95% CI, 99.60-99.72%). RDT sensitivity depended on viral load, with decreasing sensitivity accompanied by descending viral load. VOC-dependent sensitivity assessment showed a sensitivity of 42.86% (95% CI, 32.82-53.52%) for the wild-type SARS-CoV-2, 43.42% (95% CI, 32.86-54.61%) for the Alpha VOC, 37.67% (95% CI, 30.22-45.75%) for the Delta VOC, and 33.67% (95% CI, 25.09-43.49%) for the Omicron VOC. Sensitivity in samples with high viral loads of ≥10RDT sensitivity for detection of the Omicron VOC is reduced in individuals infected with a high viral load, which curtails the effectiveness of RDTs. This aspect furthert: limits the use of RDTs, although RDTs are still an irreplaceable diagnostic tool for rapid, economic point-of-care and extensive SARS-CoV-2 screening.

BackgroundCOVID-19 vaccination is a key prevention strategy to reduce the spread and severity of SARS-CoV-2 infections, especially among highly exposed healthcare workers (HCWs). However, vaccine-related inability to work among HCWs could overstrain healthcare systems.MethodsThis study examined sick leave and intake of pro re nata (PRN) medication after the first, second and third COVID-19 vaccination in HCWs. Subgroup analyses were performed for different vaccines, gender, healthcare professions, and for HCWs aged at least 30 years. Data was collected by using an electronic questionnaire.FindingsAmong 1,704 HCWs enrolled, in total 595 (34·9%) HCWs were on sick leave following at least one COVID-19 vaccination, leading to a total number of 1,550 sick days. Both the absolute sick days and the rate of HCWs on sick leave significantly increased with each subsequent vaccination. Comparing BNT162b2mRNA and mRNA-1273 the difference in sick leave was not significant after the second dose, but mRNA-1273 induced a significantly longer and more frequent sick leave after the third.InterpretationA considerable number of HCWs have been on sick leave after COVID-19 vaccination, staff absences increase with each additional dose, depend on the vaccine, and vary between HCWs’ gender, and profession. In the light of further COVID-19 infection waves and booster vaccinations, there is a risk of additional staff shortages due to post-vaccination inability to work, which could acutely overload healthcare systems and jeopardise patient care. These findings will aid further vaccination campaigns to minimise the impact of staff absences on the healthcare system.FundingThis study was funded by the Federal Ministry for Education and Science (BMBF) via a grant provided to the University Hospital of Wuerzburg by the Network University Medicine on COVID-19 (B-FAST, grant-No 01KX2021) as well as by the Free State of Bavaria with COVID-research funds provided to the University of Wuerzburg, Germany. Nils Petri is supported by the German Research Foundation (DFG) funded scholarship UNION CVD.

BackgroundRapid antigen detection tests (RDT) are an easily accessible, feasible, inexpensive, and point-of-care method in SARS-CoV-2 diagnostics – established in adults as well as in children and adolescents. Despite this, large-scale data of clinical performance in the paediatric population especially regarding the influence of SARS-CoV-2 virus variants of concern (VOC) and COVID-19 vaccination on test accuracy is rare.MethodsThis single-centre prospective diagnostic study evaluates three RDT (NADAL®, Panbio™, MEDsan®) in comparison to quantitative reverse transcription polymerase chain reaction (RT-qPCR). 9,760 oropharyngeal screening samples regarding SARS-CoV-2 VOC and COVID-19 vaccination in paediatric hospitalised patients aged younger than 18 years were enrolled.FindingsRDT sensitivity was 44·7% (157/351, 95% CI 39·6%–50·0%) compared to the reference standard RT-qPCR, specificity 99·8% (9,392/9,409, 95% CI 99·7%–99·9%). Most SARS-CoV-2 infections considered were caused by Omicron VOC. Diagnostic accuracy of RDT depended on specimen containing viral load with a decreasing RDT sensitivity by descending viral load, corresponding with a significantly impaired sensitivity in asymptomatic children. A sensitivity of 71·0% was obtained for a viral load higher than 106SARS-CoV-2 RNA copies per ml suggested as infectivity threshold. No significant differences in RDT sensitivity could be observed regarding gender, symptoms, COVID-19 vaccination status, and VOC.InterpretationIn a paediatric population, RDT have proven to reliably detect potentially highly infectious patients with a viral load of at least 106SARS-CoV-2 RNA copies per ml. Due to the low sensitivity in asymptomatic individuals, the usefulness of RDT seems limited in large-scale SARS-CoV-2 screening programs.FundingFederal Ministry for Education and Science (BMBF), Free State of Bavaria

In the light of emerging SARS-CoV-2 variants of concern (VOC), bivalent COVID-19 vaccines combining the wild-type spike mRNA with an Omicron VOC BA.1 or BA.4-5 spike mRNA became available. This non-randomized controlled study examined adverse reactions, PRN (pro re nata) medication intake and inability to work after a fourth COVID-19 vaccination among 76 healthcare workers. As fourth dose either the original, monovalent BNT162b2mRNA (48.7%) or the bivalent BNT162b2mRNA original/Omicron BA.4-5 vaccine (51.3%) was administered. The rate of adverse reactions for the second booster dose was significantly higher among participants receiving the bivalent 84.6% (95% CI 70.3%-92.8%; 33/39) compared to the monovalent 51.4% (95% CI 35.9-66.6%; 19/37) vaccine (p=0.0028). Also, there was a trend towards an increased rate of inability to work and intake of PRN medication following bivalent vaccination. In view of preprints reporting inconclusive results in neutralizing antibody levels between the compared vaccines, our results and further studies on safety and reactogenicity of bivalent COVID-19 booster vaccines are highly important to aid clinical decision making in the choice between bivalent and monovalent vaccinations.

Against the background of the current COVID-19 infection dynamics with its rapid spread of SARS-CoV-2 variants of concern (VOC), the immunity and the vaccine prevention of healthcare workers (HCWs) against SARS-CoV-2 continues to be of high importance. This observational cross-section study assesses factors influencing the level of anti-SARS-CoV-2-spike IgG after SARS-CoV-2 infection or vaccination. One thousand seven hundred and fifty HCWs were recruited meeting the following inclusion criteria: age ≥18 years, PCR-confirmed SARS-CoV-2 infection convalescence and/or at least one dose of COVID-19 vaccination. anti-SARS-CoV-2-spike IgG titers were determined by SERION ELISA agile SARS-CoV-2 IgG. Mean anti-SARS-CoV-2-spike IgG levels increased significantly by number of COVID-19 vaccinations (92.2 BAU/ml for single, 140.9 BAU/ml for twice and 1144.3 BAU/ml for threefold vaccination). Hybrid COVID-19 immunized respondents (after infection and vaccination) had significantly higher antibody titers compared with convalescent only HCWs. Anti-SARS-CoV-2-spike IgG titers declined significantly with time after the second vaccination. Smoking and high age were associated with lower titers. Both recovered and vaccinated HCWs presented a predominantly good humoral immune response. Smoking and higher age limited the humoral SARS-CoV-2 immunity, adding to the risk of severe infections within this already health impaired collective.

The transmission of the SARS-CoV-2 virus, which causes COVID-19, has been documented worldwide. However, the evidence of the extent to which transmission has occurred in different countries is still to be established. Understanding the magnitude and distribution of SARS-CoV-2 through seroprevalence studies is important in designing control and preventive strategies in communities. This study investigated the seropositivity of the SARS-CoV-2 virus antibodies in the communities of three different districts in the Mwanza region, Tanzania. A household cross-sectional survey was conducted in September 2021 using the modified African Centre for Disease and Prevention (ACDC) survey protocol. A blood sample was obtained from one member of each of the selected households who consented to take part in the survey. Immunochromatographic rapid test kits were used to detect IgM and IgG SARS-CoV-2 antibodies, followed by descriptive data analysis. Overall, 805 participants were enrolled in the study with a median age of 35 (interquartile range (IQR):27–47) years. The overall SARS-CoV-2 seropositivity was 50.4% (95%CI: 46.9–53.8%). The IgG and IgM seropositivity of the SARS-CoV-2 antibodies was 49.3% and 7.2%, respectively, with 6.1% being both IgG and IgM seropositive. A history of runny nose (aOR: 1.84, 95%CI: 1.03–3.5, p = 0.036), loss of taste (aOR: 1.84, 95%CI: 1.12–4.48, p = 0.023), and living in Ukerewe (aOR: 3.55, 95%CI: 1.68–7.47, p = 0.001) and Magu (aOR: 2.89, 95%CI: 1.34–6.25, p= 0.007) were all independently associated with SARS-CoV-2 IgM seropositivity. Out of the studied factors, living in the Ukerewe district was independently associated with IgG seropositivity (aOR 1.29, CI 1.08–1.54, p = 0.004). Twenty months after the first case of COVID-19 in Tanzania, about half of the studied population in Mwanza was seropositive for SARS-CoV-2.

BackgroundA third dose of COVID-19 vaccination (‘COVID booster vaccination’) has become established as an important measure to strengthen the immune response against SARS-CoV-2. In contrast, seasonal influenza vaccination has been an important infection prevention measure for years, especially among highly exposed healthcare workers (HCWs). Coadministration of vaccines against COVID-19 and seasonal influenza could be an efficient strategy to protect HCWs from two major viral respiratory infections. Yet, the immunogenicity and safety of coadministration remains to be evaluated.MethodsThis study examines the differences in Anti-SARS-CoV-2-Spike IgG antibody formation as well as side effects based on a digital questionnaire after a third COVID-19 vaccination with or without coadministration of a seasonal quadrivalent influenza vaccine (Influvac Tetra vaccine 2021/2022). 1,231 HCWs were recruited who received a mRNA-based booster COVID-19 vaccination (mRNA-1273 or BNT162b2mRNA) after basic immunisation with BNT162b2mRNA twice. Anti-SARS-CoV-2-Spike IgG levels were determined at least 14 days after vaccination by SERION ELISA agile SARS-CoV-2 IgG.FindingsAnti-SARS-CoV-2-Spike IgG concentrations were by 25·4% lower in individuals with coadministration of the seasonal quadrivalent influenza vaccination than without (pInterpretationCoadministration of the seasonal quadrivalent influenza vaccine significantly limits the levels in Anti-SARS-CoV-2-Spike IgG levels, with a more restricted elevation in case of a BNT162b2mRNA booster vaccination compared with mRNA-1273 vaccine. The reduced humoral immune response in case of coadministration needs to be considered in seasonal vaccination recommendations, although the consequences of lower Anti-SARS-CoV-2-Spike IgG levels for the protection against SARS-CoV-2 infection and severe COVID-19 disease course are currently unknown. An augmented mRNA-based COVID-19 vaccine dosage may compensate for the restricted immunogenicity in case of coadministration.FundingThis study was funded by the Federal Ministry for Education and Science (BMBF) through a grant provided to the University Hospital of Wuerzburg by the Network University Medicine on COVID-19 (B-FAST, grant-No 01KX2021) as well as by the Free State of Bavaria with COVID-research funds provided to the University of Wuerzburg, Germany. Nils Petri is supported by the German Research Foundation (DFG) funded scholarship UNION CVD.Research in contextEvidence before this studyFor evaluation of the previously published evidence, PubMed and medRxiv were searched for the terms “influenza vaccination”, “influenza vaccine”, “influenza”, “flu”, “seasonality”, combined with “coadministration”, “concomitant”, “COVID-19 vaccination”, “COVID-19 vaccine”, “SARS-CoV-2”, in title or abstract, published between 1st of January 2020 and 18th of May 2022.To date, it is unclear if coadministration of COVID-19 and influenza vaccine is effective and safe, particularly in the cohort of healthcare workers (HCWs) as key public health stakeholders. For the subunit COVID-19 vaccine NVX-CoV2373, an impairment of Anti-SARS-CoV-2-Spike IgG levels has been shown in individuals coadministered with a seasonal influenza vaccine. The two previously published studies on coadministration of a mRNA-based COVID-19 and a seasonal quadrivalent influenza vaccine have reported a restriction of humoral Anti-SARS-CoV-2-Spike immune response in the coadministration group. These examinations were conducted with limited correspondence to real-life conditions and in smaller cohorts. Additionally, these former studies do not consider the important aspect of side effects as a possible direct effect of the prevention measure on the availability of public health care in combination with Anti-SARS-CoV-2-Spike IgG levels. In summary, the humoral immunogenicity and side effects of a coadministered third COVID-19 and a seasonal influenza vaccine are still unclear and the limited available data is not transferable to the general public.Added value of this studyWe performed the first large-scale real-life evaluation of humoral immunogenicity and side effects of COVID-19 and influenza vaccine coadministration in HCWs. Anti-SARS-CoV-2-Spike IgG levels were significantly lower in the coadministered cohort compared to the not coadministered control group, stratified by third COVID-19 vaccine (BNT162b2mRNA or mRNA-1273). Anti-SARS-CoV-2-Spike IgG post-vaccine elevation was lower among BNT162b2mRNA vaccinated HCWs than in those vaccinated with mRNA-1273 as a third COVID-19 vaccination. The influence of the seasonal quadrivalent influenza vaccine is evaluated in a cohort including 1,231 HCWs in total, covering a broad age range. Coadministration did not lead to an increase in side effects, which is a central requirement for considering the option of coadministration, given the role of HCWs as key personnel in maintaining health care capacities.Implications of all the available evidenceOur data suggest, that coadministration of third mRNA-based COVID-19 and quadrivalent seasonal influenza vaccine is safe and immunogenic, although it leads to a slightly reduced Anti-SARS-CoV-2-Spike antibody formation. While the clinical impact of the observed reduction in humoral Anti-SARS-CoV-2-Spike immune response for protection against SARS-CoV-2 infection and severe COVID-19 disease is still unclear, influenza vaccination remains an important infection prevention measure, especially among highly exposed HCWs. The coadministration does not increase side effects but may improve vaccination rate. A higher-dosed mRNA-based COVID-19 vaccine may compensate for the restricted immunogenicity in case of seasonal influenza vaccine coadministration. Our results will support the development of public health recommendations for coadministration of COVID-19 and influence vaccines in anticipation of the imminent infection waves in the coming winter season.

Background Haemophilus influenzae can cause invasive infections, in which cefotaxime is among the first-line antibiotics for treatment. The prevalence of cefotaxime-resistant H. influenzae in Europe is reported to be on a low level. Nevertheless, systematic studies with a large set of invasive isolates are scarce. Objectives To provide prevalence data for cefotaxime resistance in invasive H. influenzae isolates in Germany 2016–19 and investigate the epidemiological relevance of PBP3 mutations known to elevate the cefotaxime MIC. Methods Cefotaxime susceptibility of invasive H. influenzae isolates, collected in the national laboratory surveillance programme, was examined by gradient agar diffusion (GAD) testing. Cefotaxime resistance was determined according to EUCAST guidelines (resistance breakpoint MIC >0.125 mg/L). Therefore, the MIC for all resistant isolates was verified by broth microdilution method (BMD). WGS was performed to investigate the genetic relationship of cefotaxime-resistant isolates and to analyse alterations in the PBP3. An analysis of the geographic distribution of the resistant isolates was performed. Results From 2016 to 2019, the German National Reference Laboratory for Meningococci and H. influenzae received 2432 invasive H. influenzae isolates from blood and CSF. According to GAD results, 27 strains were resistant to cefotaxime. BMD confirmed the resistance in 22 of these isolates, which equals a prevalence of cefotaxime resistance of 0.90% in invasive H. influenzae in Germany. Among cefotaxime-resistant isolates cgMLST revealed three clusters. PBP3 analysis showed previously described mutations in our strains. In comparison with cefotaxime-susceptible strains, the alterations L389F and Y557H were significantly associated with cefotaxime resistance, but were not present in all resistant strains. Geographic analysis showed that the disease cases with cefotaxime-resistant H. influenzae were evenly spread throughout the population in Germany. Conclusions Cefotaxime is still well suited for the treatment of invasive H. influenzae infections. Rarely occurring cefotaxime resistance is caused by sporadic mutations. The role of PBP3 mutations needs further investigation.

The term complementary and alternative medicine (CAM) describes a broad spectrum of health care practices that are not an integral part of the conventional health care system. Many patients worldwide use CAM on their own initiative, often in combination with their conventional medical therapy. CAM use is attractive especially to patients with primary immunodeficiency, since they suffer from frequent infections and autoimmunity. Those are frequently addressed by CAM providers. The aim of this multicentric study was to collect information on the use of CAM by these patients and to define characteristics that are associated with the use of CAM. A total of 101 patients with primary immunodeficiencies at German hospitals were surveyed on their CAM use (further 14 patients rejected to participate). Multiple psychological tests (MARS-D, WHO-5, PHQ9, EFQ) were conducted to investigate variations among personality traits associated with CAM use. Additionally, clinical and sociodemographic patient data was collected. A total of 72% of patients used CAM to treat their primary immunodeficiency. The three most frequently used methods were physical exercise or fitness training (65%), dietary supplements (58%), and homeopathy (49%). Most patients did not discuss CAM use with their doctors, mostly because they felt that there was no time for it. CAM plays an important role for patients with primary immunodeficiency in a high-resource health care setting such as Germany. In clinical practice, doctors should create a platform to discuss needs that go beyond conventional therapy.

Background Post-exposure prophylaxis (PEP) for close contacts of invasive meningococcal disease (IMD) cases is recommended in most countries to avoid secondary cases by eradicating supposed meningococcal colonization. Currently, rifampicin, ciprofloxacin and ceftriaxone are recommended in many countries including Germany. Azithromycin has been shown to eradicate meningococcal colonization. Objectives To assess the azithromycin susceptibility of invasive Neisseria meningitidis isolates. Methods A subset of German invasive meningococcal isolates from 2006–18 was selected for this study. Azithromycin MIC was determined using broth microdilution and agar gradient diffusion. Results Azithromycin MICs as determined by broth microdilution ranged from Conclusions Azithromycin is an eligible antibiotic for PEP of IMD close contacts. It is approved for adults as well as children and may even be used in pregnancy. Because of easier application and lower toxicity, it might be an alternative to rifampicin and ciprofloxacin, as we found no resistant isolates. Since a gonococcal gene associated with elevated azithromycin MICs has been reported in N. meningitidis, careful monitoring of the emergence of resistant strains is nevertheless necessary for meningococci. Lack of concordance of MICs between broth microdilution and agar gradient diffusion needs to be considered.

BackgroundAntigen rapid diagnostic tests (RDT) for SARS-CoV-2 are fast, broadly available, and inexpensive. Despite this, reliable clinical performance data is sparse.MethodsIn a prospective performance evaluation study, RDT from three manufacturers (NADAL®, Panbio™, MEDsan®) were compared to quantitative reverse transcription polymerase chain reaction (RT-qPCR) in 5 068 oropharyngeal swabs for detection of SARS-CoV-2 in a hospital setting. Viral load was derived from standardized RT-qPCR Cycle threshold (Ct) values. The data collection period ranged from November 12, 2020 to February 28, 2021.FindingsOverall, sensitivity of RDT compared to RT-qPCR was 42·57% (95% CI 33·38%–52·31%), and specificity 99·68% (95% CI 99·48%–99·80%). Sensitivity declined with decreasing viral load from 100% in samples with a deduced viral load of ≥108SARS-CoV-2 RNA copies per ml to 8·82% in samples with a viral load lower than 104SARS-CoV-2 RNA copies per ml. No significant differences in sensitivity or specificity could be observed between the three manufacturers, or between samples with and without spike protein variant B.1.1.7. The NPV in the study cohort was 98·84%; the PPV in persons with typical COVID-19 symptoms was 97·37%, and 28·57% in persons without or with atypical symptoms.InterpretationRDT are a reliable method to diagnose SARS-CoV-2 infection in persons with high viral load. RDT are a valuable addition to RT-qPCR testing, as they reliably detect infectious persons with high viral loads before RT-qPCR results are available.FundingGerman Federal Ministry for Education and Science (BMBF), Free State of BavariaResearch in contextEvidence before this studyWe searched PubMED an MedRxiv for articles including “COVID-19”, “COVID”, “SARS-CoV-2”, “coronavirus” as well as “antigen detection”, “rapid antigen test”, “Point-of-Care test” in title or abstract, published between January 1, 2020 and February 28, 2021. The more than 150 RDT on the market at the end of February 2021 represent a huge expansion of diagnostic possibilities.1Performance of currently available RDT is evaluated in several international studies, with heterogeneous results. Sensitivity values of RDT range from 0·0%2to 98·3%3, specificity from 19·4%4to 100·0%.2,5–14. Some of this data differs greatly from manufacturers’ data. However, these previously published performance evaluation studies were conducted under laboratory conditions using frozen swabs, or in small cohorts with middle-aged participants. Comparable RDT performance data from large-scale clinical usage is missing.5–19Added value of this studyBased on previous examinations the real life opportunities and limitations of SARS-CoV-2 RDT as an instrument of hospital infection detection and control are still unclear as well as further study results are limited in transferability to general public. Our findings show that RDT performance in daily clinical routine is reliable in persons with high viral for punctual detection and isolation of infectious persons before RT-qPCR become available. In persons with lower viral load, or in case of asymptomatic patients SARS-CoV2 detection by RDT was unsuccessful. The general sensitivity of 42·57% is too low to accept the RDT in clinical use as an alternative to RT-qPCR in diagnosis of COVID-19. Calculated specificity was 99.68%. The results are based on a huge study cohort with more than 5 000 participants including a representative ages structure with pediatric patients up to geriatric individuals, which portrays approximately the demographic structure of the local society.Implications of all the available evidenceDue to the low general sensitivity RDT in clinical use cannot be accepted as an alternative but as an addition to RT-qPCR in SARS-CoV-2 diagnosis. The benefit of early detection of highly infectious persons has to be seen in context of the effort of testing and isolation of false positive tested persons.

The aim of the present study was to assess the prevalence of medication-related osteonecrosis of the jaw (MRONJ) in osteoporosis patients suffering from inflammatory rheumatic diseases, as well as to assess the prevalence of relevant dental, behavioral, and medical risk factors for MRONJ. A total of 198 patients with inflammatory rheumatic diseases and osteoporosis therapy were recruited from a tertiary rheumatological/immunological referral center between June 2015 and September 2016. They were assessed using a structured interview. A maxillofacial surgeon later examined patients complaining of possible symptoms of osteonecrosis. In cases of osteonecrosis, dental records were obtained and evaluated. Preventive measures taken and dental as well as other clinical risk factors were evaluated. Of the 198 patients, three suffered from osteonecrosis of the jaw, none of whom had any history of malignant disease or radiation therapy, resulting in a prevalence of 1.5%. Of these three patients, only one was given bisphosphonates intravenously (i.v.), whereas all three had been treated orally. All three diagnoses of MRONJ had been previously known to the patients and their maxillofacial surgeons. Two of the patients had rheumatoid arthritis, and one patient suffered from large vessel vasculitis. Long anti-osteoporotic treatment duration, low functional status, and low bone density of the femur were significantly associated with MRONJ development. Inflammatory rheumatic diseases constitute a risk factor for MRONJ in patients treated with bisphosphonates for osteoporosis. Patients should be counseled accordingly and should be offered dental screening and regular dental check-ups.

For the control of immunity in COVID-19 survivors and vaccinated subjects there is an urgent need for reliable and rapid serological assays.Based on samples from 63 COVID-19 survivors up to seven months after symptom onset, and on 50 serum samples taken before the beginning of the pandemic, we compared the performance of three commercial immunoassays for the detection of SARS-CoV-2 IgA and IgG antibodies (Euroimmun SARS-COV-2 IgA/IgG, Mikrogen recomWell SARS-CoV-2 IgA/IgG, and SERION ELISA agile SARS-CoV-2 IgA/IgG) and three rapid lateral flow (immunochromatographic) tests (Abbott Panbio COVID-19 IgG/IgM, NADAL COVID-19 IgG/IgM, and Cleartest Corona 2019-nCOV IgG/IgM) with a plaque-reduction neutralization test (PRNT50) representing the gold standard. In addition, we report and validate a novel, non-commercial flow cytometry bead-based surrogate test.57 out of 63 PCR-confirmed COVID-19 patients (90 %) showed neutralizing antibodies. The sensitivity of the seven assays ranged from 7.0 % to 98.3 %, the specificity from 86.0 % to 100.00 %. Only one commercial immunoassay showed a sensitivity and specificity of greater than 98 %. These data indicate abundant interassay variability.

Elderly care facilities have become a major focus of coronavirus disease (COVID-19) control. Here, we describe an outbreak of COVID-19 in a nursing home in Germany from 8 March to 4 May 2020 (58 days), and the effect of an intervention of general screening and cohort isolation. COVID-19 cases among residents and staff were recorded on a daily basis from the first positive SARS-CoV-2 test from a resident on 8 March 2020, until 4 May 2020 when the last staff member was classified COVID-19 negative. Eighty of 160 residents (50%) and 37 of 135 staff members (27%) tested positive for SARS-CoV-2. Twenty-seven of the 80 residents were asymptomatic but tested positive during the first general screening. Cohort isolation of SARS-CoV-2 positive residents by reorganising the facility proved to be a major effort. After the intervention, four further asymptomatic residents tested positive in follow-up screenings within a period of 6 days, and were possibly infected prior to the intervention. Thereafter, no further infections were recorded among residents. The described outbreak was controlled by implementing general screening and rigorous cohort isolation, providing a blueprint for similar facilities.

Anamnestic screening of symptoms and contact history is applied to identify coronavirus disease 2019 (COVID-19) patients on admission. However, asymptomatic and presymptomatic patients remain undetected although the viral load may be high. In this retrospective cohort study, all hospitalized patients who received polymerase chain reaction (PCR) admission testing from March 26th until May 24th, 2020 were included. Data on COVID-19-specific symptoms and contact history to COVID-19 cases were retrospectively extracted from patient files and from contact tracing notes. The compliance to the universal testing protocol was high with 90%. Out of 6940 tested patients, 27 new severe acute respiratory syndrome coronavirus-2 infections (0.4%) were detected. Seven of those COVID-19 cases (26% of all new cases) were asymptomatic and had no positive contact history, but were identified through a positive PCR test. The number needed to identify an asymptomatic patient was 425 in the first wave of the epidemic, 1218 in the low incidence phase. The specificity of the method was above 99.9%. Universal PCR testing was highly accepted by staff as demonstrated by high compliance. The costs to detect one asymptomatic case in future studies need to be traded off against the costs and damage caused by potential outbreaks of COVID-19.

BackgroundHaemophilus influenzae (Hi) serotype b (Hib) vaccination was introduced in Germany in 1990. This study presents a comprehensive overview on the burden of invasive Hi infections for 2001–2016, including serotype distribution and ampicillin resistance.MethodsNationwide data from statutory disease surveillance (2001–2016) were linked with laboratory surveillance data (2009–2016). Besides descriptive epidemiology, statistical analyses included multiple imputation to estimate secular trends.ResultsIn 2001–2016, 4044 invasive Hi infections were reported. The mean incidence was 3.0 per million inhabitants, higher in males (3.2 vs 2.9 in females) and in the age groups ConclusionsThis is one of the most comprehensive Hi data analyses since the introduction of Hib vaccines. NTHi and Hif cause an increasing disease burden among elderly patients and infants. Ampicillin resistance in NTHi must be considered in the treatment of invasive Hi infections.

Haemophilus influenzae can cause respiratory and invasive infections ([1][1]), whereas H. haemolyticus (Hh) is generally considered apathogenic ([2][2]) and is rarely associated with disease ([3][3]). Since both species colonize the upper respiratory tract, their distinction is crucial in routine

Introduction Invasive meningococcal disease (IMD) is a rare condition with a high case fatality rate. While most patients suffer from one single episode in life, there is anecdotal evidence for recurrent infection. Aim The German National Reference Laboratory for Meningococci and Haemophilus influenzae (NRZMHi) analysed IMD cases from 2002 to 2018 to retrospectively quantify the risk of recurrent infection. Methods Recurrent IMD was defined as detection of Neisseria meningitidis in a sample of the same patient more than 30 days after the first episode of IMD. Results Among 5,854 patients with a median observation period of 9.4 years, 14 suffered a second IMD episode and one patient a third one. The risk of a recurrent IMD was 29.4 per 100,000 person-years for survivors of the first episode. Rare serogroups (Y, W, E and Z) were more common in patients with recurrent IMD (p Discussion Patients surviving IMD were at least at a 50-fold risk of another IMD episode compared with the general population. The study most likely underestimated the risk of recurrent infection. Increased risk may be due to undiagnosed complement deficiencies. The high risk of re-infection argues for vaccination of patients who have survived IMD.

Background The total incidence of invasive meningococcal disease (IMD) in Europe has been declining in recent years; however, a rising incidence due to serogroup W (MenW), predominantly sequence type 11 (ST-11), clonal complex 11 (cc11), was reported in some European countries. Aim The aim of this study was to compile the most recent laboratory surveillance data on MenW IMD from several European countries to assess recent trends in Europe. Methods In this observational, retrospective study, IMD surveillance data collected from 2013–17 by national reference laboratories and surveillance units from 13 European countries were analysed using descriptive statistics. Results The overall incidence of IMD has been stable during the study period. Incidence of MenW IMD per 100,000 population (2013: 0.03; 2014: 0.05; 2015: 0.08; 2016: 0.11; 2017: 0.11) and the proportion of this serogroup among all invasive cases (2013: 5% (116/2,216); 2014: 9% (161/1,761); 2015: 13% (271/2,074); 2016: 17% (388/2,222); 2017: 19% (393/2,112)) continuously increased. The most affected countries were England, the Netherlands, Switzerland and Sweden. MenW was more frequent in older age groups (≥ 45 years), while the proportion in children ( Conclusion During the years 2013–17, an increase in MenW IMD, mainly caused by MenW cc11, was observed in the majority of European countries. Given the unpredictable nature of meningococcal spread and the epidemiological potential of cc11, European countries may consider preventive strategies adapted to their contexts.

Hepatitis B virus (HBV) reactivation is a common complication of immunosuppressive treatment in high prevalence countries. Biological disease-modifying antirheumatic drugs (bDMARDs) cause this adverse event more often than conventional immunosuppressants. The incidence of HBV reactivation during treatment for rheumatic diseases in Germany is unclear. Furthermore, it remains open how to treat and monitor patients at risk during immunosuppressive therapy with bDMARDs. We examined 2054 patients from a German tertiary rheumatology center in order to analyze the prevalence of HBc-antibody-positivity and the incidence of HBV reactivation in German rheumatology patients treated with immunosuppressants. Of 1317 patients treated with bDMARDs and 737 conventional synthetic DMARD (csDMARDs) patients between 2008 and 2017, 86 had a history of HBV infection (anti-HBc positive). Only two patients were suffering from chronic infection (HBsAg positive). Three patients were treated pre-emptively with entecavir, and eight patients after HBV DNA reappearance. No liver failure occurred due to HBV reactivation. Compared to anti-HBc-positive patients without reactivation, the reactivation group included more patients exposed to three or more classes of bDMARDs (p = 0.017). The median HBs antibody titer was significantly lower in the reactivation group (15.0 IU/l vs. 293.5 IU/l; p = 0.001). This study shows that bDMARDs and csDMARDs can safely be administered to patients with a history of HBV, provided they are closely monitored. Low titers of anti-HBs antibodies and a history of ≥ 3 classes of immunosuppressants increase the risk of HBV reactivation. These data highlight major differences to high prevalence regions.

Public funding for medical research in Germany is primarily provided by the German Research Foundation (DFG) and the Federal Ministry of Education and Research (BMBF). The aim of this study was to analyze the amount of national public funding for medical research on predominant causes of death in Germany, cardiovascular diseases and neoplasms, in relation to the burden of these diseases in Germany. Three evaluators categorized medical research projects funded by the DFG or BMBF between 2010 and 2012 into the categories “Diseases of the circulatory system” (with subgroups “Ischemic heart diseases”, “Heart failure” and “Cerebrovascular diseases”) and “Neoplasms”. The total amount of public funding by the national agencies was analyzed in relation to the burden of disease for the respective disease condition. Information on national public funding for medical research of 2091 million euros was available; of those, 246.8 million euros (11.8%) were categorized being spent for research on “Neoplasms”, 118.4 million euros (5.7%) for research on “Diseases of the circulatory system”. This results in 362.08 euros per case of death, 16.58 euros per year of life lost (YLL) and 16.04 euros per disability-adjusted life year (DALY) for “Neoplasms” and in 113.44 euros per case of death, 8.05 euros per YLL and 7.17 euros per DALY for “Diseases of the circulatory system”. In Germany, research on cardiovascular diseases receives a lower share of national public funding for medical research compared to oncological research. These results are comparable to other European countries.