A SARS-CoV2 super-spreading event occurred during carnival in a small town in Germany. Due to the rapidly imposed lockdown and its relatively closed community, this town was seen as an ideal model to investigate the infection fatality rate (IFR). Here, a 7-day seroepidemiological observational study was performed to collect information and biomaterials from a random, household-based study population. The number of infections was determined by IgG analyses and PCR testing. We found that of the 919 individuals with evaluable infection status, 15.5% (95% CI:[12.3%; 19.0%]) were infected. This is a fivefold higher rate than the reported cases for this community (3.1%). 22.2% of all infected individuals were asymptomatic. The estimated IFR was 0.36% (95% CI:[0.29%; 0.45%]) for the community and 0.35% [0.28%; 0.45%] when age-standardized to the population of the community. Participation in carnival increased both infection rate (21.3% versus 9.5%, p < 0.001) and number of symptoms (estimated relative mean increase 1.6, p = 0.007). While the infection rate here is not representative for Germany, the IFR is useful to estimate the consequences of the pandemic in places with similar healthcare systems and population characteristics. Whether the super-spreading event not only increases the infection rate but also affects the IFR requires further investigation.

In the current COVID‐19 pandemic, a better understanding of the relationship between merely binding and functionally neutralizing antibodies is necessary to characterize protective antiviral immunity following infection or vaccination. This study analyzes the level of correlation between the novel quantitative EUROIMMUN Anti‐SARS‐CoV‐2 QuantiVac ELISA (IgG) and a microneutralization assay. A panel of 123 plasma samples from a COVID‐19 outbreak study population, preselected by semiquantitative anti‐SARS‐CoV‐2 IgG testing, was used to assess the relationship between the novel quantitative ELISA (IgG) and a microneutralization assay. Binding IgG targeting the S1 antigen was detected in 106 (86.2%) samples using the QuantiVac ELISA, while 89 (72.4%) samples showed neutralizing antibody activity. Spearman's correlation analysis demonstrated a strong positive relationship between anti‐S1 IgG levels and neutralizing antibody titers ( r s = 0.819, p < 0.0001). High and low anti‐S1 IgG levels were associated with a positive predictive value of 72.0% for high‐titer neutralizing antibodies and a negative predictive value of 90.8% for low‐titer neutralizing antibodies, respectively. These results substantiate the implementation of the QuantiVac ELISA to assess protective immunity following infection or vaccination.

Memory B cells seem to be more durable than antibodies and thus crucial for the long-term immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here we investigate SARS-CoV-2 spike-specific memory B cells and their dependence on CD4 + T cell help in different settings of coronavirus disease 2019 . Compared with severely ill individuals, those who recovered from mild COVID-19 develop fewer but functionally superior spike-specific memory B cells. Generation and affinity maturation of these cells is best associated with IL-21 + CD4 + T cells in recovered individuals and CD40L + CD4 + T cells in severely ill individuals. The increased activation and exhaustion of memory B cells observed during COVID-19 correlates with CD4 + T cell functions. Intriguingly, CD4 + T cells recognizing membrane protein show a stronger association with spike-specific memory B cells than those recognizing spike or nucleocapsid proteins. Overall, we identify CD4 + T cell subsets associated with the generation of B cell memory during SARS-CoV-2 infection.

Prolonged breath-hold causes complex compensatory mechanisms such as increase in blood pressure, redistribution of blood flow, and bradycardia. We tested whether apnea induces an elevation of catecholamine-concentrations in well-trained apneic divers.11 apneic divers performed maximal dry apnea in a horizontal position. Parameters measured during apnea included blood pressure, ECG, and central, in addition to peripheral hemoglobin oxygenation. Peripheral arterial hemoglobin oxygenation was detected by pulse oximetry, whereas peripheral (abdominal) and central (cerebral) tissue oxygenation was measured by Near Infrared Spectroscopy (NIRS). Exhaled O and CO, plasma norepinephrine and epinephrine concentrations were measured before and after apnea.Averaged apnea time was 247±76 s. Systolic blood pressure increased from 135±13 to 185±25 mmHg. End-expiratory CO increased from 29±4 mmHg to 49±6 mmHg. Norepinephrine increased from 623±307 to 1 826±984 pg ml and epinephrine from 78±22 to 143±65 pg ml during apnea. Heart rate reduction was inversely correlated with increased norepinephrine (correlation coefficient -0.844, p=0.001). Central (cerebral) O desaturation was time-delayed compared to peripheral O desaturation as measured by NIRS and SpO.Increased norepinephrine caused by apnea may contribute to blood shift from peripheral tissues to the CNS and thus help to preserve cerebral tissue O saturation longer than that of peripheral tissue.

Our study demonstrated the high diagnostic power of well-known biomarkers. LOCI™-based tumor marker assays give reliable results in routine diagnostics.

BackgroundThe Manchester Triage System (MTS) does not have a specific presentational flow chart for sepsis. The goal of this investigation was to determine adequacy of acuity assignment for patients with sepsis presenting at the ED and triaged using the MTS. Materials and methods This retrospective analysis included patients >16 presenting to an ED in Bonn, Germany, on the first 12 days of each month between June 2012 and March 2014. Patients were classified into one of three septic groups, or no sepsis. For those with sepsis, adequacy of acuity assignment was based on the criteria of the first consensus conference of the American College of Chest Physicians and Society of Critical Care Medicine, first published in 1992. Adequacy of prioritisation is expressed as sensitivity and likelihood ratio (LR-). Results Among 20 836 patients evaluated, 801 (3.8%) were septic; of these, 581 (72.5%) had sepsis, 194 (24.2%) had severe sepsis and 26 (3.2%) had severe sepsis with circulation dysfunction. Patients who met the criteria for sepsis were correctly prioritised with a sensitivity of 70.4% (95% CI 66.5 to 74.0). The LR-was 0.628 (95% CI 0.564 to 0.698). Patients with severe sepsis were appropriately prioritised with a sensitivity of 84.5% (95% CI 78.1 to 89.4), and LR-was 0.330 (95% CI 0.243 to 0.450). In the group with severe sepsis and circulation dysfunction, sensitivity of MTS was 61.5% (95% CI 39.3 to 79.8), and LR-was 0.466 (95% CI 0.286 to 0.757). Conclusions The MTS has some weaknesses regarding priority levels in emergency patients with septic illness. Overall, target key symptoms (discriminators) which aim at identifying systemic infection and ascertaining vital parameters are insufficiently considered.

BackgroundProlonged breath holding results in hypoxemia and hypercapnia. Compensatory mechanisms help maintain adequate oxygen supply to hypoxia sensitive organs, but burden the cardiovascular system.The aim was to investigate human compensatory mechanisms and their effects on the cardiovascular system with regard to cardiac function and morphology, blood flow redistribution, serum biomarkers of the adrenergic system and myocardial injury markers following prolonged apnoea.MethodsSeventeen elite apnoea divers performed maximal breath-hold during cardiovascular magnetic resonance imaging (CMR). Two breath-hold sessions were performed to assess (1) cardiac function, myocardial tissue properties and (2) blood flow. In between CMR sessions, a head MRI was performed for the assessment of signs of silent brain ischemia. Urine and blood samples were analysed prior to and up to 4 h after the first breath-hold.ResultsMean breath-hold time was 297 ± 52 s. Left ventricular (LV) end-systolic, end-diastolic, and stroke volume increased significantly (p < 0.05). Peripheral oxygen saturation, LV ejection fraction, LV fractional shortening, and heart rate decreased significantly (p < 0.05). Blood distribution was diverted to cerebral regions with no significant changes in the descending aorta. Catecholamine levels, high-sensitivity cardiac troponin, and NT-pro-BNP levels increased significantly, but did not reach pathological levels.ConclusionCompensatory effects of prolonged apnoea substantially burden the cardiovascular system. CMR tissue characterisation did not reveal acute myocardial injury, indicating that the resulting cardiovascular stress does not exceed compensatory physiological limits in healthy subjects. However, these compensatory mechanisms could overly tax those limits in subjects with pre-existing cardiac disease. For divers interested in competetive apnoea diving, a comprehensive medical exam with a special focus on the cardiovascular system may be warranted.Trial registrationThis prospective single-centre study was approved by the institutional ethics committee review board. It was retrospectively registered under ClinicalTrials.gov (Trial registration: NCT02280226. Registered 29 October 2014).Electronic supplementary materialThe online version of this article (10.1186/s12968-018-0455-x) contains supplementary material, which is available to authorized users.

Evidence is sparse regarding the clinical performance of luminescent oxygen channeling immunoassays-based tumor marker assays in gynecological cancer. Analyzing serum samples of 336 patients with Dimension™Vista1500, we investigated the diagnostic power of carbohydrate antigen 15-3, carbohydrate antigen 125, carcinoembryonic antigen, carbohydrate antigen 19-9, and alpha-fetoprotein in patients suffering from different types of gynecological cancer and precancerous gynecological diseases and compared findings to appropriate control groups. The cohort comprised 177 female patients with gynecological cancers (73 breast, 22 cervical, 16 endometrial, 17 vulva, and 49 ovarian cancers), 26 patients with precancerous gynecological diseases (11 vulva, 4 cervical, and 10 breast), 109 patients with benign gynecological diseases, and 24 healthy controls. Discriminative power was assessed by areas under the curve in receiver operating characteristic curves, and sensitivities were determined at a fixed specificity of 95%. Levels of biomarkers in healthy controls were in the expected ranges and a discriminative power between gynecological cancers and healthy controls was observed for several tumor markers. Established tumor type-associated markers were elevated in specific gynecological cancers and benign controls as well as within precancerous gynecological diseases and healthy control group. In ovarian cancer, carbohydrate antigen 125 and carbohydrate antigen 15-3 were significantly elevated compared to the respective benign diseases. Carbohydrate antigen 125 was the most conclusive marker (area under the curve = 0.86% and 77.6% sensitivity at 95% specificity). In breast cancer, carcinoembryonic antigen and carbohydrate antigen 15-3 were significantly higher than in the respective benign diseases. Carcinoembryonic antigen achieved the most conclusive area under the curve (0.65) with 31.5% sensitivity at 95% specificity. None of the investigated markers was found to be of value in discriminating benign and malignant cervical diseases. Carcinoembryonic antigen and alpha-fetoprotein distinguished precancerous breast and vulva diseases from healthy controls. These findings show that luminescent oxygen channeling immunoassays-based tumor marker assays provide reliable results in routine diagnostics.