key: cord-1018009-2itui3ar authors: Schwierzeck, Vera; König, Jens Christian; Kühn, Joachim; Mellmann, Alexander; Correa-Martínez, Carlos Luis; Omran, Heymut; Konrad, Martin; Kaiser, Thomas; Kampmeier, Stefanie title: First reported nosocomial outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a pediatric dialysis unit date: 2020-04-27 journal: Clin Infect Dis DOI: 10.1093/cid/ciaa491 sha: e0f04e6b29837e2b1d6821e01a047cfdb715c1ea doc_id: 1018009 cord_uid: 2itui3ar BACKGROUND: Coronavirus disease 2019 (COVID-19) is a life-threatening respiratory condition caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was initially detected in China in December 2019. Currently, in Germany over 140,000 cases of COVID-19 are confirmed. Here we report a nosocomial outbreak of SARS-CoV-2 infections in the pediatric dialysis unit of the University Hospital of Münster (UHM). METHODS: Single-step real-time RT-PCR from nasopharyngeal swaps was used to diagnose the index patient and identify infected contacts. Epidemiological links were analyzed by patient interviews and chart reviews. In addition, each contact was assessed for exposure to the index case and monitored for clinical symptoms. Threshold cycle (C(t)) values of all positive test results were compared between symptomatic and asymptomatic cases. RESULTS: Forty-eight cases were involved in this nosocomial outbreak. Nine contact cases developed laboratory confirmed COVID-19 infections. Two SARS-CoV-2 positive cases remained clinically asymptomatic. Eleven cases reported flu-like symptoms without positive results. C(t) values were significantly lower in cases presenting typical COVID-19 symptoms, suggesting high viral shedding (p =0.007). CONCLUSION: Person-to-person transmission was at the heart of a hospital outbreak of SARS-CoV-2 between healthcare workers (HCWs) and patients in the pediatric dialysis unit at the UHM. Semi quantitative real-time RT-PCR results suggest that individuals with high viral load pose a risk to spread SARS-CoV-2 in the hospital setting. Our epidemiological observation highlights the need to develop strategies to trace and monitor SARS-CoV-2 infected HCWs in order to prevent COVID-19 outbreaks in the hospital setting. In December 2019, SARS-CoV-2, a novel B lineage betacoronavirus was discovered in Wuhan City, Hubei province, China [1, 2] . SARS-CoV-2 causes COVID-19, a severe respiratory syndrome that is associated with fever, cough, dyspnoea, myalgia and fatigue [3] . On March 11 th , 2020 the WHO declared COVID-19 a pandemic and currently SARS-CoV-2 infections pose a serious threat to health care systems worldwide [4] . SARS-CoV-2 is the third member of the coronaviridae family, with the Severe Acute Respiratory Syndrome-Coronavirus (SARS-CoV) and the Middle East Respiratory Syndrome Virus (MERS-CoV), to cause major epidemic outbreaks in the last twenty years [2, 5, 6] . Recent studies demonstrate that SARS-CoV-2 is more contagious than SARS-CoV and MERS-CoV [7] . While persistence of SARS-CoV-2 has been described on inert surfaces, person-to-person transmission via droplets is believed to be the main mode of transmission followed by an incubation period of five days on average before onset of illness [2, 7, 8] . Several publications have described nosocomial transmission for the current COVID-19 pandemic [9, 10] . It has been estimated that more than 3,300 health care workers (HCWs) in China have been infected with SARS-CoV-2 during the outbreak and in Italy, an estimated 20% of those infected were HCWs [11] . However, detailed epidemiological characterization of transmission chains in the hospital setting remains scarce. Consequently, there is concern that infection control measures are not adequate to prevent SARS-CoV2 transmissions between individuals in healthcare settings. The first COVID-19 case in Germany was diagnosed on January 27 th , 2020 and the first case of SARS-CoV-2 infection at the UHM was detected on February 29 th , 2020 [12] . The UHM is a 1,500-bed university hospital in the federal state of North-Rhine-Westphalia (NRW), Germany with a catchment area of 310,000 inhabitants. By the beginning of April over 140,000 cases of COVID-19 have been detected in Germany and over 29,000 cases of COVID-19 in the region of NRW [13] . Here we describe an outbreak of SARS-CoV-2 among 28 HCWs, 13 patients and seven accompanying persons (ACP) at the pediatric dialysis unit of the UHM. Recently the European Dialysis (EUDIAL) working group of the European Renal Association-European Dialysis Transplant Association (ERA-EDTA) has classified uremic patients on hemodialysis as a risk group for COVID-19 infection due to an impaired immune system, high burden of comorbidities and frequent hospitalization [7] . As the pandemic continues to spread, it will be important to establish effective infection Patients, ACP and HCW were interviewed to identify COVID-19-typical symptoms (n=11) each day, for ten days, and trace additional individuals that had contact with the index case while symptomatic. Persons with contact to SARS-CoV-2 infected individuals were assessed for their type of exposure with the help of a risk-based questionnaire, adopted from the guidelines issued by the Robert-Koch Institute (RKI), Germany's national Public Health Institute. The criteria considered for the different types of exposure were duration of exposure, personal protective equipment (PPE) used during exposure, distance to the infective source and potential infectivity of body fluids (table 1). In case of suspected or confirmed SARS-CoV-2 infections personnel was instructed to wear filtering face peace (FFP)-2 masks, unsterile gloves and gowns for PPE. For aerosol-generating procedures goggles were additionally recommended. The outbreak was defined as two or more COVID-19 infections resulting from a common exposure, that was either suspected or laboratory-confirmed as SARS-CoV-2. After identification, the outbreak was reported to the local public health department. In addition, 7 following the recommendations of the RKI for hygienic measures (table 1) , patients were pre-emptively isolated. Alternatively, if an outpatient treatment was necessary due to their underlying diseases, i.e. hemodialysis, patients were cohorted together with their ACP. Swab sampling and laboratory testing Following internal standard operating procedures for specimen collection, nasopharyngeal swabs of all persons with contact to the index case were collected from day 5 onwards ((after the index case was confirmed on day 4). If first test showed a negative result but contact cases presented new or worsened symptoms, testing was repeated.SARS-CoV-2 was detected by specific assays targeting two separate genes via real-time RT-PCR as described previously [14] . Detection of envelope (E) gene was used as a screening test and detection of RNA-dependent RNA polymerase (RdRp) gene was used for confirmation. The threshold cycle value (C t value), which is inversely proportional to the viral load, was documented for every SARS-CoV-2 positive sample. Statistical analysis was performed using the Student's t-test. Statistical significance was declared at p < 0·05. Involved outbreak cases and outbreak dynamics 48 cases (28 HCWs, 13 patients, and seven ACP) were involved in the outbreak, including index case and contact cases. The average age of HCWs was 46 years, of patients was 10 years and of ACP was 32 years. In total 15 cases were of male, 33 of female sex. All patients suffer from chronic kidney disease with the majority being on regular hemodialysis. After contact to the index case, nine contact cases (seven HCWs, one patient and one ACP) developed laboratory confirmed COVID-19 infections. All of these were categorized as type I or Ib-exposure, according to mentioned criteria (table 1) . No contact was categorized as Ia. In total, four of eight type I and seven of seven type Ib contacts became infected. No type II contact was tested SARS-CoV-2 positive. Additionally, two patients were tested positively for SARS-CoV-2 but did not present apparent COVID-19 symptoms. Another 11 HCWs affirmed common cold symptoms without being tested positively. No case reported dyspnea (figure 1, Covid-19 is currently a public health relevant pandemic that will increase hospital admissions for severe acute respiratory disorders. In addition, hospital acquired COVID-19 infections are a potential route of transmission and pose a threat to vulnerable inpatients and HCWs. We characterized a nosocomial outbreak of SARS-CoV-2 on a pediatric dialysis unit that involved 48 cases including patients, ACP and HCWs. Detailed contact investigation and initial laboratory testing identified an index case and infected contact cases confirming previous findings that person-to-person transmission is also the most likely mode of transmission in the hospital setting [15] . Part of our outbreak investigation was a detailed assessment of clinical symptoms associated with COVID-19 infection. Interestingly, two infected children with chronic kidney disease either presented a very mild phenotype or even remained asymptomatic, despite considered to be at particular risk for respiratory infections because of hemodialysis [16, 17] . This might confirm reports that children suffering from COVID-19 often present with relatively mild symptoms [18] . However, the majority of confirmed cases became symptomatic with body aches accompanied with flank and loin pain, fatigue and headache. Similar to influenza, infected individuals described loss of taste and smell several days after onset of illness. This is consistent with statements of the British Association of Otorhinolaryngology and the American Academy of Otolaryngology-Head and Neck Surgery reporting dysgeusia and anosmia in COVID-19 patients [19, 20] . This particular symptoms should be investigated in larger epidemiological cohorts [21] . Previous studies suggest better positive predictive values if tests are performed in symptomatic individuals [22] . Our findings in HCW25 seem to corroborate these findings: whereas the initial test was negative after contact to the index case without any symptoms, the HCW was positively tested three days later after development of clinical signs of a SARS-CoV-2 infection. Since lower C t values and therefore higher viral load were detected in symptomatic patients and HCWs, our observations give a first hint to support this testing strategy for the hospital setting. For example HCW1 (index case) experienced fever on day 2 resulting in a low C t value when she was tested two days later. As many healthcare systems are facing the problem of reduced laboratory testing capacity, based on our results we are cautious to recommend testing asymptomatic contacts but would preferably monitor clinical key symptoms. On the other hand, individuals with high viral load could potentially serve as a source of transmissions, supporting the theory of so-called super-spreaders [23] . During the outbreak management, we classified contacts according to duration and severity of exposure (see table1). While only cases with type I/Ib exposure became symptomatic, several other cases with type I/Ib exposure did not develop symptoms. This result suggests that an exposure-based classification is not specific enough to discriminate high risk from no risk contacts. However, this recommendation in combination with infection control measures allows key personnel to continue work while self-monitoring symptoms. This strategy can be used to maintain an adequate healthcare service while facing staff shortages during the current SARS-CoV-2 pandemic. Summarizing, our investigation suggests that application of appropriate infection control measures including contact tracing, assessment of exposure and optimal symptom-based testing strategies are essential to prevent outbreaks of SARS-CoV-2 within hospital settings. Type of exposure A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster A pneumonia outbreak associated with a new coronavirus of probable bat origin Clinical features of patients infected with 2019 novel coronavirus in Wuhan WHO. 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The Lancet Observations on excess mortality associated with epidemic influenza Severe acute respiratory syndrome in dialysis patients Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study. The Lancet Infectious Diseases Loss of sense of smell as marker of COVID-19 infection AAO-HNS: Anosmia, Hyposmia, and Dysgeusia Symptoms of Coronavirus Disease Association of decreased rate of influenza vaccination with increased subjective olfactory dysfunction Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study. The Lancet Infectious Diseases Transmission characteristics of MERS and SARS in the healthcare setting: a comparative study We thank the patients and staff at the Pediatric Nephrology unit for their collaboration during this investigation and the team of the Institute of Virology for excellent laboratory work.Funding DFG Clinical research unit 342. The funding institution had no role in the study design, data collection, analysis and interpretation, writing the manuscript or decision for publication. The corresponding authors had full access to all data in the study and final responsibility for the decision to submit for publication. The authors declare that they have no potential conflicts of interest. HCW11 II -no ----HCW12 II -yes ----HCW13 II -no ----HCW14 II -no ----HCW15 II -yes ----HCW16 II -no ----HCW17 II -no ----HCW18 II -yes ----HCW19 II -no ----HCW20 II -no ----HCW21 II -no ----HCW22 II -no ----HCW23 II -