Results of a monocentric field study: value of histology compared to sonication method and conventional tissue culture in the diagnosis of periprosthetic joint infection (PJI).

BACKGROUND: To confirm the diagnosis of periprosthetic joint infection (PJI), the Infectious Diseases Society of America (IDSA) and the International Consensus Meeting (ICM) have defined criteria that include histology as a minor criterion and the sonication method only as an additional criterion. The aim of this monocentric, retrospective study was to investigate the value of histology and whether sonication leads to a more accurate diagnosis. MATERIALS AND METHODS: All revision surgeries for knee and hip arthroplasty between 2017 and 2020 were included. With regard to microbiological diagnostic, conventional culture of periprosthetic biopsies and sonication of explant material were performed. In addition, histology and non-specific inflammatory markers (CRP, leukocytes) were recorded. RESULTS: A total of 78 patients with PJI and 62 aseptic controls were included. From both microbiological methods (conventional culture / sonication), Staphyloccus (S.) epidermidis and S. aureus were detected most frequently. However, compared to the conventional microbiology, a higher sensitivity was calculated for sonication, albeit with a lower specificity in relation to a PJI. In two logistic regression models for the significance of all diagnostic parameters in PJI, the AUC was 0.92 and 0.96 with histology in particular making the decisive contribution in both models (p < 0. 001, both models). CONCLUSION: Since histology showed the highest accuracy in the current study, its importance in the PJI criteria should be reevaluated. Sonication shows a high sensitivity for germ detection with a lower specificity and should only be used in combination with the conventional culture for microbiolgical diagnostics.

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.

Comparative analysis of RSV-related hospitalisations in children and adults over a 7 year-period before, during and after the COVID-19 pandemic.

BACKGROUND: RSV is an important cause for respiratory illness in children and the elderly. We analysed RSV seasons since 2016 in both age groups for differences, similarities and timely associations before, during and after the COVID-19 pandemic. METHODS: We studied epidemiological and clinical features of seven consecutive RSV seasons since 2016 retrospectively in children and adults who were systematically monitored for RSV infections by PCR when hospitalized in Regensburg, Germany. RESULTS: Data from 1903 RSV positive, hospitalised patients were analysed (1446 children, 457 adults). We observed a complete absence of RSV associated hospitalizations in season 2020/2021. While in the season of 2021/2022, RSV associated hospitalizations in children returned to considerable numbers earlier than expected, hospitalizations in the elderly were still mitigated during that season in temporal association with the continuation of NPI measures for COVID-19 in the elderly until summer of 2022. Overall, children were hospitalized more often for RSV, while the elderly showed more severe outcomes. RSV hospitalisations continuously increase in both age groups, following a bi-annual pattern of severe and less severe seasons, which was not altered by the COVID-19 pandemic. CONCLUSION: We demonstrate the relation between RSV waves in children and the elderly. NPI measures may protect the elderly from RSV infections and epidemiological data could be used to predict RSV waves early enough to prepare countermeasures.

Serum Neurofilament light chain (NfL) levels in children with and without neurologic diseases.

BACKGROUND/OBJECTIVE: Serum neurofilament light chain (sNfL) is a specific biomarker of neuronal damage. Elevated sNfL levels have been reported in numerous neurologic diseases in adults, whereas data on sNfL in the pediatric population are incomplete. The aim of this study was to investigate sNfL levels in children with various acute and chronic neurologic disorders and describe the age dependence of sNfL from infancy to adolescence. METHODS: The total study cohort of this prospective cross-sectional study consisted of 222 children aged from 0 to 17 years. Patients' clinical data were reviewed and patients were assigned to the following groups: 101 (45.5%) controls, 34 (15.3%) febrile controls, 23 (10.4%) acute neurologic conditions (meningitis, facial nerve palsy, traumatic brain injury, or shunt dysfunction in hydrocephalus), 37 (16.7%) febrile seizures, 6 (2.7%) epileptic seizures, 18 (8.1%) chronic neurologic conditions (autism, cerebral palsy, inborn mitochondrial disorder, intracranial hypertension, spina bifida, or chromosomal abnormalities), and 3 (1.4%) severe systemic disease. sNfL levels were measured using a sensitive single-molecule array assay. RESULTS: There were no significant differences in sNfL levels between controls, febrile controls, febrile seizures, epileptic seizures, acute neurologic conditions, and chronic neurologic conditions. In children with severe systemic disorders, by far the highest NfL levels were found with an sNfL of 429 pg/ml in a patient with neuroblastoma, 126 pg/ml in a patient with cranial nerve palsy and pharyngeal Burkitt's lymphoma, and 42 pg/ml in a child with renal transplant rejection. The relationship between sNfL and age could be described by a second order polynomial with an R2 of 0.153 with a decrease of sNfL by 3.2% per year from birth to age 12 years and thereafter an increase by 2.7% per year until age 18 years. CONCLUSIONS: In this study cohort, sNfL levels were not elevated in children with febrile or epileptic seizures, or various other neurologic diseases. Strikingly high sNfL levels were detected in children with oncologic disease or transplant rejection. A biphasic sNfL age-dependency was documented, with highest levels in infancy and late adolescence and the lowest levels in middle school age.

Focusing on severe infections with the respiratory syncytial virus (RSV) in adults: Risk factors, symptomatology and clinical course compared to influenza A / B and the original SARS-CoV-2 strain.

BACKGROUND: The role and impact of RSV in the adult population is not well understood and comparative data of RSV infection, influenza A/B and SARS-CoV-2 in the elderly hospitalized for respiratory infections is limited. METHODS: In a retrospective, monocentric study we analyzed data of adult patients with respiratory infections tested positive by PCR for RSV, Influenza A/B and SARS-CoV-2 over a four-year period from 2017 to 2020. Symptoms on admission, laboratory results, and risk factors were assessed, and the clinical course and outcomes were studied. RESULTS: A total of 1541 patients hospitalized with respiratory disease and PCR positive for one of the 4 viruses were enrolled in the study. RSV was the second most prevalent virus before the COVID-19 pandemic and RSV patients represent the oldest group in this study with an average age of 75 years. Neither clinical nor laboratory characteristics differ clearly between RSV, Influenza A / B and SARS-CoV-2 infections. Up to 85% of patients had risk factors, with COPD and kidney disease found particularly frequently in RSV infections. Hospital stay was 12.66 days for RSV patients and thus significantly longer than for influenza A / B (10.88 and 8.86, respectively, p < 0.001), but shorter than for SARS-CoV-2 (17.87 days, p < 0.001). The risk for ICU admission and the rate of mechanical ventilation were also higher for RSV than for influenza A (OR 1.69 (p = 0.020) and 1.59 (p = 0.050)) and influenza B: (1.98 (p = 0.018) and 2.33 (p < 0.001)), but lower than for SARS-CoV-2 (0.65 (p < 0.001) and 0.59 (p = 0.035)). The risk of hospital mortality for RSV was increased compared with influenza A (1.55 (p = 0.050)) and influenza B (1.42 (p = 0.262)), but lower compared to SARs-CoV-2 (0.37 (p < 0.001). CONCLUSION: RSV infections in elderly are frequent and more severe than those with influenza A/B. While the impact of SARS-CoV-2 most likely decreased in the elderly population due to vaccination, RSV can be expected to continue to be problematic for elderly patients, especially those with comorbidities and thus, more awareness on the disastrous impact of RSV in this age group is urgently needed.

Analysis of COVID-19 Infection Chains in a School Setting: Data From a School-Based rRT-PCR-Gargle Pool Test System.

BACKGROUND: School testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was implemented in some countries to monitor and prevent SARS-CoV-2 transmissions. Here, we analyze infection chains in primary schools and household members of infected students based on systematic real-time reverse-transcriptase polymerase-chain-reaction (rRT-PCR)-gargle pool testing. METHODS: Students and school staff (N = 4300) of all 38 primary schools in the rural county of Cham, Germany, were tested twice per week with a gargle pool rRT-PCR system from April to July of 2021. Infection chains of all 8 positive cases identified by school testing were followed up. RESULTS: In total, 8 positive cases were found by gargle pool PCR testing based on 96,764 school tests. While no transmissions occurred in the school setting, 20 of 27 household members of the 8 cases tested positive. The overall attack rate was 74.1% in families. CONCLUSIONS: No school outbreaks occurred during the study period. All cases but 1 were initially picked up by school testing. No transmission from school to families was observed.

Results of WICOVIR Gargle Pool PCR Testing in German Schools Based on the First 100,000 Tests.

Background: Opening schools and keeping children safe from SARS-CoV-2 infections at the same time is urgently needed to protect children from direct and indirect consequences of the COVID-19 pandemic. To achieve this goal, a safe, efficient, and cost-effective SARS-CoV-2 testing system for schools in addition to standard hygiene measures is necessary. Methods: We implemented the screening WICOVIR concept for schools in the southeast of Germany, which is based on gargling at home, pooling of samples in schools, and assessment of SARS-CoV-2 by pool rRT-PCR, performed decentralized in numerous participating laboratories. Depooling was performed if pools were positive, and results were transmitted with software specifically developed for the project within a day. Here, we report the results after the first 13 weeks in the project. Findings: We developed and implemented the proof-of-concept test system within a pilot phase of 7 weeks based on almost 17,000 participants. After 6 weeks in the main phase of the project, we performed >100,000 tests in total, analyzed in 7,896 pools, identifying 19 cases in >100 participating schools. On average, positive children showed an individual CT value of 31 when identified in the pools. Up to 30 samples were pooled (mean 13) in general, based on school classes and attached school staff. All three participating laboratories detected positive samples reliably with their previously established rRT-PCR standard protocols. When self-administered antigen tests were performed concomitantly in positive cases, only one of these eight tests was positive, and when antigen tests performed after positive pool rRT-PCR results were already known were included, 3 out of 11 truly positive tests were also identified by antigen testing. After 3 weeks of repetitive WICOVIR testing twice weekly, the detection rate of positive children in that cohort decreased significantly from 0.042 to 0.012 (p = 0.008). Interpretation: Repeated gargle pool rRT-PCR testing can be implemented quickly in schools. It is an effective, valid, and well-received test system for schools, superior to antigen tests in sensitivity, acceptance, and costs.

Symptoms, SARS-CoV-2 Antibodies, and Neutralization Capacity in a Cross Sectional-Population of German Children.

Background: Children and youth are affected rather mildly in the acute phase of COVID-19 and thus, SARS-CoV-2 infection infection may easily be overlooked. In the light of current discussions on the vaccinations of children it seems necessary to better identify children who are immune against SARS-CoV-2 due to a previous infection and to better understand COVID-19 related immune reactions in children. Methods: In a cross-sectional design, children aged 1-17 were recruited through primary care pediatricians for the study (a) randomly, if they had an appointment for a regular health check-up or (b) if parents and children volunteered and actively wanted to participate in the study. Symptoms were recorded and two antibody tests were performed in parallel directed against S (in house test) and N (Roche Elecsys) viral proteins. In children with antibody response in either test, neutralization activity was determined. Results: We identified antibodies against SARS-CoV-2 in 162 of 2,832 eligible children (5.7%) between end of May and end of July 2020 in three, in part strongly affected regions of Bavaria in the first wave of the pandemic. Approximately 60% of antibody positive children (n = 97) showed high levels (>97th percentile) of antibodies against N-protein, and for the S-protein, similar results were found. Sufficient neutralizing activity was detected for only 135 antibody positive children (86%), irrespective of age and sex. Initial COVID-19 symptoms were unspecific in children except for the loss of smell and taste and unrelated to antibody responses or neutralization capacity. Approximately 30% of PCR positive children did not show seroconversion in our small subsample in which PCR tests were performed. Conclusions: Symptoms of SARS-CoV-2 infections are unspecific in children and antibody responses show a dichotomous structure with strong responses in many and no detectable antibodies in PCR positive children and missing neutralization activity in a relevant proportion of the young population.

Performance evaluation of the Roche Elecsys Anti-SARS-CoV-2 S immunoassay.

The Elecsys® Anti-SARS-CoV-2 S immunoassay (Roche Diagnostics International Ltd, Rotkreuz, Switzerland) has been developed for the detection of antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein. We evaluated the assay performance using samples from seven sites in Germany, Austria, and Switzerland. For specificity and sensitivity analyses, 7880 presumed negative pre-pandemic samples and 827 SARS-CoV-2 PCR-confirmed single or sequential samples from 272 different patients were tested, respectively. The overall specificity and sensitivity (≥14 days post-PCR) for the Elecsys Anti-SARS-CoV-2 S immunoassay were 99.95% (95% confidence interval [CI]: 99.87-99.99; 7876/7880) and 97.92% (95% CI: 95.21-99.32; 235/240), respectively. The Elecsys Anti-SARS-CoV-2 S immunoassay had significantly higher specificity compared with the LIAISON® SARS-CoV-2 S1/S2 IgG (99.95% [2032/2033] vs 98.82% [2009/2033]), ADVIA Centaur® SARS-CoV-2 Total (100% [928/928] vs 86.96% [807/928]), ARCHITECT SARS-CoV-2 IgG (99.97% [2931/2932] vs 99.69% [2923/2932]), iFlash-SARS-CoV-2 IgM (100.00% [928/928] vs 99.57% [924/928]), and EUROIMMUN Anti-SARS-CoV-2 IgG (100.00% [903/903] vs 97.45% [880/903]) and IgA (100.00% [895/895] vs 95.75% [857/895]) assays. The Elecsys Anti-SARS-CoV-2 S immunoassay had significantly higher sensitivity (≥14 days post-PCR) compared with the ARCHITECT SARS-CoV-2 IgG (98.70% [76/77] vs 87.01% [67/77]), iFlash-SARS-CoV-2 IgG (100.00% [76/76] vs 93.42% [71/76]) and IgM (100.00% [76/76] vs 35.53% [27/76]), and EUROIMMUN Anti-SARS-CoV-2 IgG (98.26% [113/115] vs 93.91% [108/115]) assays. Therefore, the Elecsys Anti-SARS-CoV-2 S assay demonstrated a reliable performance across various sample populations for the detection of anti-S antibodies.

SARS-CoV-2 in pregnancy and possible transfer of immunity: assessment of peripartal maternal and neonatal antibody levels and a longitudinal follow-up.

OBJECTIVES: In the current Severe Acute Respiratory Distress Coronavirus 2 (SARS-CoV-2) pandemic there is still great uncertainty about the effects of an infection in pregnancy especially regarding a possible fetal transmission of antibodies to SARS-CoV-2 and the longevity of this immunity. METHODS: Sixteen women who were infected with SARS-CoV-2 during pregnancy and their offspring were included. The antibody response to SARS-CoV-2 was measured in mother and umbilical cord blood peripartum and in a follow-up examination 6-11 weeks after birth. Medical history, symptoms regarding SARS-CoV-2, obstetric and neonatal information were queried following recommendations by the WHO. RESULTS: A total of 73% of the women and one third of the infants developed antibodies to SARS-CoV-2 spike (S) protein receptor binding domain (RBD), with a long interval between infection and birth proving favorable for a transplacentar transfer of antibodies to the neonates. All infants showed declining or vanishing antibody-titers in the follow-up examination, while the titers of their mothers were stable or even increased. CONCLUSIONS: Our results demonstrate that transplacental transfer of SARS-CoV-2-specific antibodies is possible, but also indicate that the immunity that may be gained as a result might decrease in newborns postpartum. This provides important evidence that could be useful for further studies covering vaccination during pregnancy.

Peripartal anti-SARS-CoV-2-IgA/IgG in asymptomatic pregnant women during regional SARS-CoV-2-outbreak.

OBJECTIVES: The Severe Acute Respiratory Distress Corona Virus 2 (SARS-CoV-2) pandemic poses special challenges for the society and especially the medical staff. Even if a rather mild course is assumed among pregnant women the measures to prevent transmission of the infection are of outstanding importance. METHODS: To screen asymptomatic pregnant women during admission to our university maternal hospital we focused on anti-SARS-CoV-2-specific IgG and IgA antibody responses. Hundred and fifty one women admitted to the hospital for childbirth or caesarean delivery were included. In case of suspicious anti-SARS-CoV-2-antibody levels an RT-PCR was performed to confirm an ongoing infection with SARS-CoV-2. RESULTS: A total of 89% showed negative results for anti-SARS-CoV-2-IgA antibodies, whereas 3% were borderline and 7% positive (both labeled as suspicious). In only one patient with suspicious serology we detected SARS-CoV-2-RNA in the following RT-PCR. 2% presented anti-SARS-CoV-2-IgG antibodies, all being positive for anti-SARS-CoV-2-IgA. The observed positive rate of our study collective of 10.6% seemed much higher than the expected one (1.3%) based on the reports of the Robert Koch Institute and the specifications given by the test's manufacturer. The expected positive predictive value (PPV) was 4.3-6.7 times higher than the observed one. CONCLUSIONS: To our knowledge this is the first report of anti-SARS-CoV-2-antibody levels in the peripartum period of asymptomatic women. As the positive anti-SARS-CoV-2 serology poorly correlated with the confirmatory RT-PCR and the fact that mainly the detection of the virus by PCR correlates with the patient's infectiousness we suggest to rather perform a SARS-CoV-2-PCR-based admission screening in perinatal centers to prevent the spread of the disease.

Effect of a strict hygiene bundle for the prevention of nosocomial transmission of SARS-CoV-2 in the hospital: a practical approach from the field.

BACKGROUND: During the novel coronavirus disease (COVID-19) pandemic it is crucial for hospitals to implement infection prevention strategies to reduce nosocomial transmission to the lowest possible number. This is all the more important because molecular tests for identifying SARS-CoV-2 infected patients are uncertain, and the resources available for them are limited. In this view, a monocentric, retrospective study with an interventional character was conducted to investigate the extent to which the introduction of a strict hygiene bundle including a general mask requirement and daily screening for suspicious patients has an impact on the SARS-CoV-2 nosocomial rate in the pandemic environment. METHODS: All inpatients from a maximum care hospital in Regensburg (Bavaria) between March 1st and June 10th 2020 were included. Patient with respiratory symptoms were tested for SARS-CoV-2 at admission, patients were managed according to a standard hygiene protocol. At the end of March a strict hygiene bundle was introduced including a general mask obligation and a daily clinical screening of inpatients for respiratory symptoms. Nosocomial infection rate for COVID-19 and the risk for infection transmission estimated by the nosocomial incidence density before and after introduction the hygiene bundle were compared. The infection pressure for the hospital during the entire observational period was characterized by the infection reports in the region in relation to the number of hospitalized COVID-19 patients and the number of infected employees. RESULTS: In fact, after the introduction of a strict hygiene bundle including a general mouth and nose protection obligation and a daily clinical screening of suspicious patients, a significant reduction of the nosocomial rate from 0.28 to 0.06 (p = 0.026) was observed. Furthermore, the risk of spreading hospital-acquired infections also decreased dramatically from 0.0007 to 0.00018 (p = 0.031; rate ratio after/before 0.25 (95%CI 0.06, 1.07) despite a slow decrease of the hospital COVID 19-prevalence and an increase of infected employees. CONCLUSION: The available data underline that a strict hygiene bundle seem to be associated with a decrease of nosocomial SARS-CoV-2 transmission in the pandemic situation.

Immune response to SARS-CoV-2 in health care workers following a COVID-19 outbreak: A prospective longitudinal study.

OBJECTIVE: Currently, little is known about the progression of an immune response against SARSCoV- 2 upon infection or sub-infection-exposure over time. We examined the serologic response in healthcare workers up to 12 weeks after a well-documented and contained outbreak and compared results with findings from earlier serologic testing in the same population. METHODS: This study followed 166 health care workers of the University Perinatal Care Center, Regensburg, Germany, for up to 12 weeks. 27 of the subjects had previously tested positive for the presence of SARS-CoV-2 by PCR testing and developed COVID-19. Serologic responses were tested with two independent commercially available test kits. RESULTS: 77.8 % of COVID-19 study subjects developed a specific IgG-response over the course of the 12-week study, while none of the COVID-19 contact groups had a detectable IgG response. Amongst most COVID-19 patients the values of detectable IgG-responses significantly increased over time as confirmed with both tests, while that of positive IgA responses decreased. Between the number of reported symptoms and antibody responses in COVID-19 patients no correlation was found and no new cases of seroconversion were identified in asymptomatic coworkers with negative PCR during the outbreak. CONCLUSIONS: Immune response after COVID-19 increases significantly over time but still approximately 22 % of COVID-19 patients did not mount a measurable serologic immune response within 60 days. Exposed co-workers did not develop any relevant antibody levels at all. We conclude that immunity after infection increases over time, but the antibody response does not develop reliably in all infected people.

An epidemic CC1-MRSA-IV clone yields false-negative test results in molecular MRSA identification assays: a note of caution, Austria, Germany, Ireland, 2020.

We investigated why a clinical meticillin-resistant Staphylococcus aureus (MRSA) isolate yielded false-negative results with some commercial PCR tests for MRSA detection. We found that an epidemic European CC1-MRSA-IV clone generally exhibits this behaviour. The failure of the assays was attributable to a large insertion in the orfX/SCCmec integration site. To ensure the reliability of molecular MRSA tests, it is vital to monitor emergence of new SCCmec types and junction sites.

SARS-CoV-2 antibody testing-questions to be asked.

Severe acute respiratory syndrome coronavirus 2 infection and development of coronavirus disease 2019 presents a major health care challenge of global dimensions. Laboratory diagnostics of infected patients, and the assessment of immunity against severe acute respiratory syndrome coronavirus 2, presents a major cornerstone in handling the pandemic. Currently, there is an increase in demand for antibody testing and a large number of tests are already marketed or are in the late stage of development. However, the interpretation of test results depends on many variables and factors, including sensitivity, specificity, potential cross-reactivity and cross-protectivity, the diagnostic value of antibodies of different isotypes, and the use of antibody testing in identification of acutely ill patients or in epidemiological settings. In this article, the recently established COVID-19 Task Force of the German Society for Clinical Chemistry and Laboratory Medicine (DGKL) addresses these issues on the basis of currently available data sets in this rapidly moving field.

Symptoms and immunoglobulin development in hospital staff exposed to a SARS-CoV-2 outbreak.

BACKGROUND: Worldwide, the number of SARS-CoV-2 infections is increasing. Serological immunoglobulin tests may help to better understand the development of immune mechanisms against SARS-CoV-2 in COVID-19 cases and exposed but asymptomatic individuals. The aim of this study was to investigate exposure to SARS-CoV-2, symptoms, and antibody responses in a large sample of healthcare workers following a COVID-19 outbreak. METHODS: A COVID-19 outbreak among staff members of a major German children's and women's hospital was followed by massive RT-PCR SARS-CoV-2 tests and provided the opportunity to study symptoms, chains of infection, and SARS-CoV-2-specific antibody responses (IgG and IgA) by ELISA. Study participants were classified as COVID-19 cases, and persons with close, moderate, or no exposure to SARS-CoV-2 in the clinical setting, respectively. RESULTS: Out of 201 study participants, 31 were COVID-19 cases. While most study participants experienced many symptoms indicative for SARS-CoV-2 infection, anosmia and coughing were remarkably more frequent in COVID-19 cases. Approximately 80% of COVID-19 cases developed some specific antibody response (IgA and IgG) approximately 3 weeks after onset of symptoms. Subjects in the non-COVID-19 groups had also elevated IgG (1.8%) and IgA values (7.6%) irrespective of contact history with cases. CONCLUSION: We found that a significant number of diseased did not develop relevant antibody responses three weeks after symptom onset. Our data also suggest that exposure to COVID-19 positive co-workers in a hospital setting is not leading to the development of measurable immune responses in a significant proportion of asymptomatic contact persons.