Germany's national public health gets reorganized: A new institute shall take center stage.

In the aftermath of the COVID-19 pandemic, the German federal government recently orchestrated a fundamental change to its public health infrastructure. This reconstruction centers around the founding of a National Institute for Prevention and Education in Medicine (Bundesinstitut für Prävention und Aufklärung in der Medizin, BIPAM) at the cost of two federal institutions, the Robert Koch-Institute (RKI) and the Federal Center for Health Education (Bundeszentrale für gesundheitliche Aufklärung, BzGA). Thus, the Federal Ministry of Health (Bundesministerium für Gesundheit, BMG) plans to dissolve the BzGA and integrate its personnel into the future BIPAM. Further, all RKI research and surveillance activities related to non-communicable diseases, including AI methods development will be transferred into the BIPAM. The RKI responsibilities will solely focus on infectious diseases. According to announced plans of the BMG the primary objective for establishing the BIPAM is to address non-communicable diseases and enhance overall population health. However, the medical specialist training for public health remains non-academic at a state institution. Simultaneously the BMG already replaced two thirds of experts of the permanent commission on vaccination (Ständige Impfkommission, STIKO) and determined new procedures for appointing future expert commissioners. With these changes, Germany embarks on an extraordinary reshuffling of its national public health organizations and responsibilities, by fundamentally separating all issues around non-communicable diseases from those of infectious diseases. Germany's unraveled research tasks of public health authorities however remains unmet. Thus, 2024 marks a pivotal caesura for public health in the modern history of Germany.

Clinical and immunological benefits of full primary COVID-19 vaccination in individuals with SARS-CoV-2 breakthrough infections: A prospective cohort study in non-hospitalized adults.

BACKGROUND: SARS-CoV-2 variants of concern (VOC) may result in breakthrough infections (BTIs) in vaccinated individuals. The aim of this study was to investigate the effects of full primary (two-dose) COVID-19 vaccination with wild-type-based SARS-CoV-2 vaccines on symptoms and immunogenicity of SARS-CoV-2 VOC BTIs. METHODS: In a longitudinal multicenter controlled cohort study in Bavaria, Germany, COVID-19 vaccinated and unvaccinated non-hospitalized individuals were prospectively enrolled within 14 days of a PCR-confirmed SARS-CoV-2 infection. Individuals were visited weekly up to 4 times, performing a structured record of medical data and viral load assessment. SARS-CoV-2-specific antibody response was characterized by anti-spike-(S)- and anti-nucleocapsid-(N)-antibody concentrations, anti-S-IgG avidity and neutralization capacity. RESULTS: A total of 300 individuals (212 BTIs, 88 non-BTIs) were included with VOC Alpha or Delta SARS-CoV-2 infections. Full primary COVID-19 vaccination provided a significant effectiveness against five symptoms (relative risk reduction): fever (33 %), cough (21 %), dysgeusia (22 %), dizziness (52 %) and nausea/vomiting (48 %). Full primary vaccinated individuals showed significantly higher 50 % inhibitory concentration (IC50) values against the infecting VOC compared to unvaccinated individuals at week 1 (269 vs. 56, respectively), and weeks 5-7 (1,917 vs. 932, respectively) with significantly higher relative anti-S-IgG avidity (78% vs. 27 % at week 4, respectively). CONCLUSIONS: Full primary COVID-19 vaccination reduced symptom frequencies in non-hospitalized individuals with BTIs and elicited a more rapid and longer lasting neutralization capacity against the infecting VOC compared to unvaccinated individuals. These results support the recommendation to offer at least full primary vaccination to all adults to reduce disease severity caused by immune escape-variants.

Effects of infection control measures towards preventing SARS-CoV-2 outbreaks in a German choir boarding school from March 2020 to April 2022.

Background: Singing in a choir was associated with larger outbreaks in the beginning of the SARS-CoV-2 pandemic. Materials and methods: We report on the effect and acceptance of various infection control measures on the occurrence of SARS-CoV-2 infections in the world famous Domspatzen boys' choir from March 2020 to April 2022. Results: In addition to basic general hygiene measures, systematic rRT-PCR testing and scientifically approved concepts of distancing during singing were applied. While single infections of choir members could not be avoided, singing-related outbreaks were not observed. Until the Omicron variant emerged, potential transmission of SARS-CoV-2 in the school was limited to only one case. Incidences at the school were never higher than in the comparable general population until then. While the impact of the pandemic on daily life and singing was rated as severe, especially by staff members, most students agreed with the usefulness of protection measures and rated them as acceptable. Students viewed regular testing as the most important tool to increase safety in the school. Discussion: A bundle of infection control measures including regular testing can prevent outbreaks of SARS-CoV-2 even in the setting of choir singing. Measures are acceptable for choir members if they allow to continue with singing and performing.

Human Infections with Borna Disease Virus 1 (BoDV-1) Primarily Lead to Severe Encephalitis: Further Evidence from the Seroepidemiological BoSOT Study in an Endemic Region in Southern Germany.

More than 40 human cases of severe encephalitis caused by Borna disease virus 1 (BoDV-1) have been reported to German health authorities. In an endemic region in southern Germany, we conducted the seroepidemiological BoSOT study ("BoDV-1 after solid-organ transplantation") to assess whether there are undetected oligo- or asymptomatic courses of infection. A total of 216 healthy blood donors and 280 outpatients after solid organ transplantation were screened by a recombinant BoDV-1 ELISA followed by an indirect immunofluorescence assay (iIFA) as confirmatory test. For comparison, 288 serum and 258 cerebrospinal fluid (CSF) samples with a request for tick-borne encephalitis (TBE) diagnostics were analyzed for BoDV-1 infections. ELISA screening reactivity rates ranged from 3.5% to 18.6% depending on the cohort and the used ELISA antigen, but only one sample of a patient from the cohort with requested TBE diagnostics was confirmed to be positive for anti-BoDV-1-IgG by iIFA. In addition, the corresponding CSF sample of this patient with a three-week history of severe neurological disease tested positive for BoDV-1 RNA. Due to the iIFA results, all other results were interpreted as false-reactive in the ELISA screening. By linear serological epitope mapping, cross-reactions with human and bacterial proteins were identified as possible underlying mechanism for the false-reactive ELISA screening results. In conclusion, no oligo- or asymptomatic infections were detected in the studied cohorts. Serological tests based on a single recombinant BoDV-1 antigen should be interpreted with caution, and an iIFA should always be performed in addition.

IFN-γ-Based ELISpot as a New Tool to Detect Human Infections with Borna Disease Virus 1 (BoDV-1): A Pilot Study.

More than 40 human infections with the zoonotic Borna disease virus 1 (BoDV-1) have been reported to German health authorities from endemic regions in southern and eastern Germany. Diagnosis of a confirmed case is based on the detection of BoDV-1 RNA or BoDV-1 antigen. In parallel, serological assays such as ELISA, immunoblots, and indirect immunofluorescence are in use to detect the seroconversion of Borna virus-reactive IgG in serum or cerebrospinal fluid (CSF). As immunopathogenesis in BoDV-1 encephalitis appears to be driven by T cells, we addressed the question of whether an IFN-γ-based ELISpot may further corroborate the diagnosis. For three of seven BoDV-1-infected patients, peripheral blood mononuclear cells (PBMC) with sufficient quantity and viability were retrieved. For all three patients, counts in the range from 12 to 20 spot forming units (SFU) per 250,000 cells were detected upon the stimulation of PBMC with a peptide pool covering the nucleocapsid protein of BoDV-1. Additionally, individual patients had elevated SFU upon stimulation with a peptide pool covering X or phosphoprotein. Healthy blood donors (n = 30) and transplant recipients (n = 27) were used as a control and validation cohort, respectively. In this pilot study, the BoDV-1 ELISpot detected cellular immune responses in human patients with BoDV-1 infection. Its role as a helpful diagnostic tool needs further investigation in patients with BoDV-1 encephalitis.

COVID-19-related deaths: a 2-year inter-wave comparison of mortality data from Germany.

PURPOSE: The severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has caused substantial mortality worldwide. We investigated clinical and demographic features of COVID-19-related deaths that occurred between March 2020 and January 2022 in Regensburg, Germany. METHODS: We compared data across four consecutive time periods: March 2020 to September 2020 (period 1), October 2020 to February 2021 (period 2), March 2021 to August 2021 (period 3), and September 2021 to January 2022 (period 4). RESULTS: Overall, 405 deaths in relation to COVID-19 were reported. The raw case fatality ratio (CFR) was 0.92. In periods 1 to 4, the CFRs were 1.70%, 2.67%, 1.06%, and 0.36%. The age-specific CFR and mortality were highest in persons aged ≥ 80 years in period 2 while mortality in younger cases increased with time. The median age at death was 84 years and it varied slightly across periods. Around 50% of cases of death were previously hospitalized. In all time periods, the cause of death was mostly attributed to COVID-19. Over the four periods, we did not find significant changes in the distribution of sex and risk factors for severe disease. The most frequent risk factor was cardio-circulatory disease. CONCLUSION: In conclusion, the CFR decreased over time, most prominently for period 4. Mortality was considerable and younger cases were increasingly at risk.

Association of epidemiological and clinical features with PCR cycle threshold values of SARS-CoV-2 infection: a cross-sectional study.

The cycle threshold (Ct) in quantitative real-time reverse-transcriptase polymerase chain reaction (qRT-PCR) is inversely correlated to the amount of viral nucleic acid or viral load and can be regarded as an indicator of infectivity. We examined the association of socio-demographic and clinical characteristics of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) polymerase chain reaction (PCR) positive cases with PCR cycle threshold (Ct) values at the time of diagnosis. SARS-CoV-2 cases reported between 12 October 2020 and 24 January 2021 in Regensburg were analyzed employing bivariate and multivariable methods. We included 3,029 SARS-CoV-2 cases (31% asymptomatic at diagnosis) and analyzed the association of case characteristics with Ct values in 2,606 cases. Among symptomatic patients, cough (38.0%), rhinitis (32.4%), headache (32.0), and fever/chills (29.9%) were the most frequent complaints. Ct values ≤20 were more frequent in symptomatic cases (20.9% vs. 11.3%), whereas Ct values >30 were more common in asymptomatic cases (32.6% vs. 18.0%). Ct values >20 and ≤30 were most common in symptomatic and asymptomatic cases (48.0% vs 40.7%). We observed lower median Ct values of E and N gene in symptomatic cases. In a random forest model, the total number of symptoms, respiratory symptoms, and age were most strongly associated with low Ct values. In conclusion, certain symptoms and age were associated with lower Ct values. Ct values can be used as a pragmatic approach in estimating infectivity at the first notification of a case and, thus, in guiding containment measures.

Authors' response: Occupation and SARS-CoV-2 infection risk among workers during the first pandemic wave in Germany: potential for bias.

We thank van Tongeren et al for responding to our study on occupational disparities in SARS-CoV-2 infection risks during the first pandemic wave in Germany (1). The authors address the potential for bias resulting from differential testing between occupational groups and propose an alternative analytical strategy for dealing with selective testing. In the following, we want to discuss two aspects of this issue, namely (i) the extent and reasons of differential testing in our cohort and (ii) the advantages and disadvantages of different analytical approaches to study risk factors for SARS-CoV-2 infection. Our study relied on nationwide prospective cohort data including more than 100 000 workers in order to compare the incidence of infections between different occupations and occupational status positions. We found elevated infection risks in personal services and business administration, in essential occupations (including health care) and among people in higher occupational status positions (ie, managers and highly skilled workers) during the first pandemic wave in Germany (2). Van Tongeren's et al main concern is that the correlations found could be affected by a systematic bias because people in healthcare professions get tested more often than employees in other professions. A second argument is that better-off people could be more likely to use testing as they are less affected by direct costs (prices for testing) and the economic hardship associated with a positive test result (eg, loss of earnings in the event of sick leave). We share the authors' view that differential testing must be considered when analysing and interpreting the data. Thus, in our study, we examined the proportion of tests conducted in each occupational group as part of the sensitivity analyses (see supplementary figure S1, accessible at www.sjweh.fi/article/4037). As expected, testing proportions were exceptionally high in medical occupations (due to employer requirements). However, we did not observe systematic differences among non-medical occupations or when categorising by skill-level or managerial responsibility. This might be explained by several reasons. First, SARS-CoV-2 testing was free of charge during the first pandemic wave in Germany, but reporting a risk contact or having symptoms was a necessary condition for testing ( https://www.bundesgesundheitsministerium.de/coronavirus/chronik-coronavirus.html (accessed 5 September 2022). The newspaper article cited by van Tongeren et al is misleading as it refers to a calendar date after our study period. Second, different motivation for testing due to economic hardship in case of a positive test result is an unlikely explanation, because Germany has a universal healthcare system, including paid sick leave and sickness benefits for all workers (3). Self-employed people carry greater financial risks in case of sickness. We therefore included self-employment in the multivariable analyses to address this potential source of bias. While the observed inverse social gradient may be surprising, it actually matches with findings of ecological studies from Germany (4, 5), the United States (6, 7) as well as Spain, Portugal, Sweden, The Netherlands, Israel, and Hong Kong (8), all of which observed higher infection rates in wealthier neighbourhoods during the initial outbreak phase of the pandemic. One possible explanation is the higher mobility of managers and better educated workers, who are more likely to participate in meetings and engage in business travel and holiday trips like skiing. Given the increasing number of studies providing evidence for this hypothesis, we conclude that the inverse social gradient in our study likely reflects different exposure probabilities and is not a result of systematic bias. This also holds true for the elevated infection risks in essential workers, which is actually corroborated by a large body of research (9-11). Regarding differential likelihood of testing, van Tongeren et al state that "[i]t is relatively simple to address this problem by using a test-negative design" (1). As van Tongeren et al describe, this is a case-control approach only including individuals who were tested (without considering those who were not tested). However, the proposed analytical strategy can lead to another (more serious) selection bias if testing proportions and/or testing criteria differ between groups (12). This can be easily illustrated when comparing the results based on a time-incidence design with those obtained by a test-negative design as shown in table 1 (see PDF). Both approaches show similar results in terms of vertical occupational differences. Infection was more common if individuals had a high skill level or had a managerial position, but associations were stronger in the time-incidence design and did not reach statistical significance in the test-negative design (as indicated by the confidence intervals overlapping "1"). Unfortunately, the test-negative approach relies on a strongly reduced sample size and thus results in greater statistical uncertainty and loss of statistical power (13). In contrast, the test-negative design yields a different picture when estimating the association between essential occupation and infection risk: In this analysis, essential workers did not differ from non-essential workers in their chance of being infected with SARS-CoV-2 (the test-negative design even exhibits a lower chance for essential workers). This is rather counter-intuitive and is not in accordance with what we know about the occupational hazards of healthcare workers during the pandemic (14). The main problem is that proportions of positive tests are highly unreliable when testing proportions and/or testing criteria differ between groups. As essential workers were tested more often without being symptomatic (due to employer requirements), a lower proportion of positive tests in this group does not necessarily correspond to a lower risk of infection. Consequently, we are not convinced that the test-negative design should be the 'gold standard' for studying risk factors for SARS-CoV-2 infections (15). Especially problematic is the loss of statistical power (increasing the probability of a type II error) and the low validity of the test-positivity when test criteria and/or test proportions differ between groups. References 1. van Tongeren M, Rhodes S, Pearce N. Occupation and SARS-CoV-2 infection risk among workers during the first pandemic wave in Germany: potential for bias. Scand J Work Environ Health 2022;48(7):586-587. https://doi.org/10.5271/sjweh.4052. 2. Reuter M, Rigó M, Formazin M, Liebers F, Latza U, Castell S, et al. Occupation and SARS-CoV-2 infection risk among 108 960 workers during the first pandemic wave in Germany. Scand J Work Environ Health 2022;48:446-56. https://doi.org/10.5271/sjweh.4037. 3. Busse R, Blümel M, Knieps F, Bärnighausen T. Statutory health insurance in Germany: a health system shaped by 135 years of solidarity, self-governance, and competition. Lancet 2017;390:882-97. https://doi.org/10.1016/S0140-6736(17)31280-1. 4. Wachtler B, Michalski N, Nowossadeck E, Diercke M, Wahrendorf M, Santos-Hövener C, et al. Socioeconomic inequalities in the risk of SARS-CoV-2 infection - First results from an analysis of surveillance data from Germany. J Heal Monit 2020;5:18-29. https://doi.org/10.25646/7057. 5. Plümper T, Neumayer E. The pandemic predominantly hits poor neighbourhoods? SARS-CoV-2 infections and COVID-19 fatalities in German districts. Eur J Public Health 2020;30:1176-80. https://doi.org/10.1093/eurpub/ckaa168. 6. Abedi V, Olulana O, Avula V, Chaudhary D, Khan A, Shahjouei S, et al. Racial, Economic, and Health Inequality and COVID-19 Infection in the United States. J Racial Ethn Heal Disparities 2021;8:732-42. https://doi.org/10.1007/s40615-020-00833-4. 7. Mukherji N. The Social and Economic Factors Underlying the Incidence of COVID-19 Cases and Deaths in US Counties During the Initial Outbreak Phase. Rev Reg Stud 2022;52. https://doi.org/10.52324/001c.35255. 8. Beese F, Waldhauer J, Wollgast L, Pförtner T, Wahrendorf M, Haller S, et al. Temporal Dynamics of Socioeconomic Inequalities in COVID-19 Outcomes Over the Course of the Pandemic-A Scoping Review. Int J Public Health 2022;67:1-14. https://doi.org/10.3389/ijph.2022.1605128. 9. Nguyen LH, Drew DA, Graham MS, Joshi AD, Guo C-G, Ma W, et al. Risk of COVID-19 among front-line health-care workers and the general community: a prospective cohort study. Lancet Public Heal 2020;5:e475-83. https://doi.org/10.1016/S2468-2667(20)30164-X. 10. Chou R, Dana T, Buckley DI, Selph S, Fu R, Totten AM. Epidemiology of and Risk Factors for Coronavirus Infection in Health Care Workers. Ann Intern Med 2020;173:120-36. https://doi.org/10.7326/M20-1632. 11. Stringhini S, Zaballa M-E, Pullen N, de Mestral C, Perez-Saez J, Dumont R, et al. Large variation in anti-SARS-CoV-2 antibody prevalence among essential workers in Geneva, Switzerland. Nat Commun 2021;12:3455. https://doi.org/10.1038/s41467-021-23796-4. 12. Accorsi EK, Qiu X, Rumpler E, Kennedy-Shaffer L, Kahn R, Joshi K, et al. How to detect and reduce potential sources of biases in studies of SARS-CoV-2 and COVID-19. Eur J Epidemiol 2021;36:179-96. https://doi.org/10.1007/s10654-021-00727-7. 13. Cohen J. Statistical Power Analysis for the Behavioral Sciences. 2nd Editio. New York: Routledge; 2013. https://doi.org/10.4324/9780203771587. 14. The Lancet. The plight of essential workers during the COVID-19 pandemic. Lancet 2020;395:1587. https://doi.org/10.1016/S0140-6736(20)31200-9. 15. Vandenbroucke JP, Brickley EB, Pearce N, Vandenbroucke-Grauls CMJE. The Evolving Usefulness of the Test-negative Design in Studying Risk Factors for COVID-19. Epidemiology 2022;33:e7-8. https://doi.org/10.1097/EDE.0000000000001438.

Health Care Workers' Sick Leave due to COVID-19 Vaccination in Context With SARS-CoV-2 Infection and Quarantine-A Multicenter Cross-Sectional Survey.

Background: Reactogenicity of coronavirus disease 2019 (COVID-19) vaccines can result in inability to work. The object of this study was to evaluate health care workers' sick leave after COVID-19 vaccination and to compare it with sick leave due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and quarantine leave. Methods: A multicenter cross-sectional survey was conducted at Regensburg University Medical Center and 10 teaching hospitals in South-East Germany from July 28 to October 15, 2021. Results: Of 2662 participants, 2309 (91.8%) were fully vaccinated without a history of SARS-CoV-2 infection. Sick leave after first/second vaccination occurred in 239 (10.4%) and 539 (23.3%) participants. In multivariable logistic regression, the adjusted odds ratio for sick leave after first/second vaccination compared with BNT162b2 was 2.26/3.72 for mRNA-1237 (95% CI, 1.28-4.01/1.99-6.96) and 27.82/0.48 for ChAdOx1-S (95% CI, 19.12-40.48/0.24-0.96). The actual median sick leave (interquartile range [IQR]) was 1 (0-2) day after any vaccination. Two hundred fifty-one participants (9.4%) reported a history of SARS-CoV-2 infection (median sick leave [IQR] 14 [10-21] days), 353 (13.3%) were quarantined at least once (median quarantine leave [IQR], 14 [10-14] days). Sick leave due to SARS-CoV-2 infection (4642 days) and quarantine leave (4710 days) accounted for 7.7 times more loss of workforce than actual sick leave after first and second vaccination (1216 days) in all fully vaccinated participants. Conclusions: Sick leave after COVID-19 vaccination is frequent and is associated with the vaccine applied. COVID-19 vaccination should reduce the much higher proportion of loss of workforce due to SARS-CoV-2 infection and quarantine.

Occupation and SARS-CoV-2 infection risk among 108 960 workers during the first pandemic wave in Germany.

OBJECTIVE: The aim of this study was to identify the occupational risk for a SARS-CoV-2 infection in a nationwide sample of German workers during the first wave of the COVID-19 pandemic (1 February-31 August 2020). METHODS: We used the data of 108 960 workers who participated in a COVID follow-up survey of the German National Cohort (NAKO). Occupational characteristics were derived from the German Classification of Occupations 2010 (Klassifikation der Berufe 2010). PCR-confirmed SARS-CoV-2 infections were assessed from self-reports. Incidence rates (IR) and incidence rate ratios (IRR) were estimated using robust Poisson regression, adjusted for person-time at risk, age, sex, migration background, study center, working hours, and employment relationship. RESULTS: The IR was 3.7 infections per 1000 workers [95% confidence interval (CI) 3.3-4.1]. IR differed by occupational sector, with the highest rates observed in personal (IR 4.8, 95% CI 4.0-5.6) and business administration (IR 3.4, 95% CI 2.8-3.9) services and the lowest rates in occupations related to the production of goods (IR 2.0, 95% CI 1.5-2.6). Infections were more frequent among essential workers compared with workers in non-essential occupations (IRR 1.95, 95% CI 1.59-2.40) and among highly skilled compared with skilled professions (IRR 1.36, 95% CI 1.07-1.72). CONCLUSIONS: The results emphasize higher infection risks in essential occupations and personal-related services, especially in the healthcare sector. Additionally, we found evidence that infections were more common in higher occupational status positions at the beginning of the pandemic.

An uncommon cause of tinea: Trichophyton violaceum in a German kindergarten - outbreak report and quantitative analysis of epidemiological data from Europe.

Background: Global mobility is increasingly associated with the emergence of "unusual" infectious agents. At the beginning of 2019, a putative outbreak of Impetigo contagiosa occurred in a kindergarten in Regensburg, Germany, that was mainly attended by children with a migrant background. After thorough examination, the outbreak was classified as infection with Trichophyton (T.) violaceum. Methods: Based on case investigations, infection control measures, disinfection, and cleaning were implemented. Microscopy of native specimens, fungal cultures, and polymerase chain reaction were used for diagnosis. Additionally, a systematic literature search in Medline, followed by a quantitative analysis of epidemiological data from Europe, were performed. Results: Between January and November 2019, 12 cases of tinea were diagnosed in 7 educators and 2 household members. Children were initially not affected. T. violaceum was only detected in 2 patients. No extensive screening measures were carried out after risk-benefit assessment. Studies on T. violaceum in Europe are heterogeneous, and the number of cases and the prevalence vary considerably. The pathogen is mainly found in children of African descent who clinically present with tinea capitis. Discussion: In the present case, the source of infection and the chain of transmission remained unclear. The pathogen could only be diagnosed in 2 cases. In Europe, the (re)emergence of pathogens such as T. violaceum is likely to be caused by increasing migration and travel. Pathogens should be identified for epidemiological reasons in all cases. In outbreaks, measures must be adapted to the dynamics of the individual outbreak after assessment of the risks, benefits, and proportionality.

Antibodies against viral nucleo-, phospho-, and X protein contribute to serological diagnosis of fatal Borna disease virus 1 infections.

Borna disease virus 1 (BoDV-1) causes rare but often fatal encephalitis in humans. Late diagnosis prohibits an experimental therapeutic approach. Here, we report a recent case of fatal BoDV-1 infection diagnosed on day 12 after hospitalization by detection of BoDV-1 RNA in the cerebrospinal fluid. In a retrospective analysis, we detect BoDV-1 RNA 1 day after hospital admission when the cell count in the cerebrospinal fluid is still normal. We develop a new ELISA using recombinant BoDV-1 nucleoprotein, phosphoprotein, and accessory protein X to detect seroconversion on day 12. Antibody responses are also shown in seven previously confirmed cases. The individual BoDV-1 antibody profiles show variability, but the usage of three different BoDV-1 antigens results in a more sensitive diagnostic tool. Our findings demonstrate that early detection of BoDV-1 RNA in cerebrospinal fluid and the presence of antibodies against at least two different viral antigens contribute to BoDV-1 diagnosis. Physicians in endemic regions should consider BoDV-1 infection in cases of unclear encephalopathy and initiate appropriate diagnostics at an early stage.

Contribution of High Viral Loads, Detection of Viral Antigen and Seroconversion to Severe Acute Respiratory Syndrome Coronavirus 2 Infectivity.

BACKGROUND: From a public health perspective, effective containment strategies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) should be balanced with individual liberties. METHODS: We collected 79 respiratory samples from 59 patients monitored in an outpatient center or in the intensive care unit of the University Hospital Regensburg. We analyzed viral load by quantitative real-time polymerase chain reaction, viral antigen by point-of-care assay, time since onset of symptoms, and the presence of SARS-CoV-2 immunoglobulin G (IgG) antibodies in the context of virus isolation from respiratory specimens. RESULTS: The odds ratio for virus isolation increased 1.9-fold for each log10 level of SARS-CoV-2 RNA and 7.4-fold with detection of viral antigen, while it decreased 6.3-fold beyond 10 days of symptoms and 20.0-fold with the presence of SARS-CoV-2 antibodies. The latter was confirmed for B.1.1.7 strains. The positive predictive value for virus isolation was 60.0% for viral loads >107 RNA copies/mL and 50.0% for the presence of viral antigen. Symptom onset before 10 days and seroconversion predicted lack of infectivity with negative predictive values of 93.8% and 96.0%. CONCLUSIONS: Our data support quarantining patients with high viral load and detection of viral antigen and lifting restrictive measures with increasing time to symptom onset and seroconversion. Delay of antibody formation may prolong infectivity.

Clinical and epidemiological data of COVID-19 from Regensburg, Germany: a retrospective analysis of 1084 consecutive cases.

BACKGROUND: COVID-19 is a syndrome caused by the recently emerged SARS-CoV-2. We collected clinical and epidemiologic data in an almost complete cohort of SARS-CoV-2 positive individuals from Regensburg, Germany, from March 2020 to May 2020. METHODS: Analysis of a retrospectively documented cohort of consecutive COVID-19 cases recorded between March 7, 2020 and May 24, 2020 as part of an infection control investigation program, with prospective follow-up interviews gathering information on type and duration of symptoms and COVID-19 risk factors until June 26, 2020. RESULTS: Of 1089 total cases, 1084 (99.5%) cases were included. The incidence during the time period was 315.4/100,000, lower than in the superordinate government district Oberpfalz (468.5/100,000) and the overall state of Bavaria (359.7/100,000). The case fatality ratio (CFR) was 2.1%. Among fatal cases, the mean age was 74.4 years and 87% presented with known risk factors, most commonly chronic heart disease, chronic lung disease, kidney disease, and diabetes mellitus. 897 cases (82.7%) showed at least one symptom, most frequently cough (45%) and fever (41%). Further, 18% of cases suffered from odour/taste disorder. 17% of total cases reported no symptoms. The median duration of general illness was 10 days. During follow-up, 8.9% of 419 interviewed cases reported at least one symptom lasting at least 6 weeks, and fatigue was the most frequent persistent symptom. DISCUSSION: We report data on type and duration of symptoms, and clinical severity of nearly all (99.5%) patients with SARS-CoV-2 recorded from March 2020 to May 2020 in Regensburg. A broad range of symptoms and symptom duration was seen, some of them lasting several weeks in a considerable number of cases. The case-fatality ratio was 2.1%. Asymptomatic cases may be underrepresented due to the nature of the study.

Changing epidemiology of COVID-19.

Background: We analyzed the epidemiology of COVID-19 in Regensburg after the first wave ended in June 2020 and compared it with patients' characteristics and symptoms in late summer/early autumn 2020. Methods: Retrospective analysis of epidemiological data from Regensburg (city/county) on age and initial symptoms as reported during case investigation for containment. Observed periods: March 7, 2020 to June 6, 2020 and August 12, 2020 to October 9, 2020. Results: The proportion of asymptomatic persons who tested positive for SARS-COV-2 in the second period was 55% (286 of 520 cases), whereas during the first wave from March to June 2020 this percentage was 14.4% (169 of 1,170 cases). A comparison of typical symptoms shows that the most common symptoms of COVID-19 in the first wave (cough, fever and generally feeling ill) were less often reported in the second period: cough 14% vs. 42%, fever 17% vs. 38%, general signs of illness 14% vs. 22% in the second vs. first period, respectively overall cases were younger in the second period, the median age of asymptomatic cases was comparable in both periods. The case fatality rate for the first period was 2.1%, in the second it was 0.2%. Discussion: The epidemiological situation in the second period is different from that during the first wave. We observed a considerable proportion of questionable cases in August/September 2020 (asymptomatic cases, high ct values, often only detection of one gene). False positive cases/non-contagious cases have to be taken into account for this period. On-demand or free-of-charge testing for asymptomatic persons will lower the positive predictive value of tests and place a high burden on finite capacities.

Can mandatory monitoring in rental apartments effectively prevent legionellosis? A retrospective analysis of data from Regensburg with a review of the literature.

Background: Legionella pneumophila can cause severe, often fatal, pneumonia in humans. Mandatory water sampling in commercially used buildings (mainly rental apartments) as regulated in the Drinking Water Ordinance (Trinkwasserverordnung) aim to protect the population against infection with Legionella. However, no data exist to date that could prove the effectiveness of the measures. At the same time, having the Public Health Department's Infection Control Division deal with Legionalla is very time consuming. Methods: A retrospective analysis of data from the city and district of Regensburg, a selective literature search, a prospective survey of workload using an anonymous questionnaire were performed. Results: The evaluated data from the city/district of Regensburg suggest underreporting to a similar extent as shown by the RKI's data in the compared period. Neither is the actual incidence known, nor can exposures be clearly determined in most cases. The exposure categories "travel" and "private/occupational" seem to be the most pertinent. The potential public hazard of Legionella posed by domestic plumbing systems is unclear. A connection between exceeding the technical measurement limit (Technischer Maßnahmenwert, TMW) in routine tests in rental apartments and disease cases cannot be shown. A survey among non-medical personnel in the field of infection control and hygiene on the time spent on the topic of Legionella yielded a mean number of 39% of daily working hours for the observed 2-month period. Conclusion: The data on incidence, exposure, and causality are incomplete. Evidence of effective protection by the current practice of sampling in apartment buildings could not be found. For many aspects, there are no unambiguous data in the literature. Restricting mandatory monitoring to certain public/commercial institutions should be discussed, given the high workload for the Public Health Department and the unproven protective effect. Further research on this topic is necessary.

Case report: 38-year-old female patient with severe legionellosis but no source of infection.

We report about a 38-year-old female patient with an extremely severe case of legionellosis. The patient had to be treated in the intensive care unit for more than a month. Extracorporeal membrane oxygenation (ECMO) had to be established in order to save the patient's life. The patient did not belong to any risk group (i.e., age >50, smoker, immunosuppression, chronic disease, male sex). Infection control investigations carried out by the Public Health Department could not reveal concrete exposures likely to cause the infection. The serotypes in the patient material (Legionella pneumophila serotype 2-14) and in the samples taken from the showerhead in the patient's apartment (Legionella pneumophila serotype 1) were not identical. Results of the examination performed according to the German Drinking Water Ordinance (Trinkwasserverordnung, TrinkwV) carried out in 2017 in the patient's apartment, showed that the technical measures limit (Technischer Maßnahmenwert, TMW) was not exceeded. The patient has survived through the extensive use and efforts of intensive care measures. In general, a concrete exposure to Legionella is often not ascertainable, as in the case presented. This raises the question of how and whether such cases of legionellosis are preventable.

Management of a measles outbreak in a reception facility for asylum seekers in Regensburg, Germany.

In July/August 2018, a measles outbreak occurred in a reception facility for asylum seekers in Regensburg, Bavaria, Germany. A five-year-old child and an 18-year-old man from Moldova were affected. At the time of the report, 491 people were accommodated at the facility. The outbreak was limited to the two cases mentioned by the consistent use of infection control measures. Decisive factors for successfully combating this outbreak were, in particular, the close cooperation of the local public health authority (Gesundheitsamt) with the district government officials, the institution's management, and the general practitioners on site. The measures taken included the early information of all parties involved, the timely and repeated implementation of containment vaccinations, a consequent segregation of contagion and/or disease suspects and the critical consideration of each individual case in connection with the separate risk-adapted segregation of particularly vulnerable cohorts.