Management of patients with suspicion of COVID-19
Due to the reports about COVID-19 spreading in Wuhan, China, a local task force was founded at the University Hospital Tuebingen, including specialists for infectious diseases, hospital hygiene and intensive care as well as virologists. This task force created the first local guidelines by the end of January 2020. In mid-February, guidelines for testing and triage of patients with suspected COVID-19 were released by the World Health Organization (WHO) and the German Public Health Institute Robert Koch Institute (RKI) [23]. Local procedures mainly followed the recommendations of the RKI, additionally guidelines were more and more adapted to local conditions during the course of the pandemic.
Initial triage measures in the children’s hospital comprised the installation of separate waiting and examination areas for suspected COVID-19 patients in the ED, including separation of patient flow. Later, a fever clinic for examination and testing of children with suspected COVID-19 was established in another part of the town. As only 18 children made use of this facility during the 2 weeks that it was operational, it was discontinued. While initially single patient rooms with airlock chambers were kept ready for paediatric COVID-19 inpatients, a separate COVID-19/respiratory infections ward with a capacity of ten beds was established by the end of May. As the ward accommodated both suspected and confirmed COVID-19 cases, it was physically separated into two areas, using a folding screen for division of the corridor. Furthermore, patients in the two areas received care provided by separate teams of nurses. Non-urgent, scheduled outpatient visits and admissions were postponed or cancelled by mid-May.
For hospital staff with direct contact to patients, a general obligation to wear surgical masks covering mouth and nose was set up by mid-March. Full personal protective equipment, including filtering facepiece (FFP) 2 masks, gowns, gloves, operation caps and goggles was provided to hospital staff involved in direct handling of patients with confirmed or suspected COVID-19. By the end of March, all patients had to wear surgical masks while being outside their rooms. By mid-May, voluntary SARS-CoV-2-RNA testing of asymptomatic hospital staff working with COVID-19 patients or in defined risk areas (haematology, PICU, ED) was established. Staff screening comprised a throat swab tested for SARS-CoV-2 RNA which was performed in the hospital and, from mid-June, also serological testing. No healthcare-associated infections with COVID-19 occurred at the children’s hospital among patients and health care staff.
The number of ED visits were significantly higher from calendar weeks 2 to 12 with a mean difference of 31.5 (95% confidence interval [CI]: 15.1–47.8, P = 0.002) visits per week in 2020 compared to the mean number of visits during the corresponding period in 2015–2019. This completely changed from calendar weeks 13 to 19, where the number of visits to the ED was significantly lower than in the previous years with a mean difference of − 72.3 (96% CI: −86.5 to − 58.1, P < 0.001) weekly visits. Figure 1 shows the ED workload, testing, triage and infection control measures during the study period.
Testing strategy and capacity
Patients were tested for SARS-CoV-2 RNA in Tuebingen starting in mid-February. While first samples were sent to the national reference centre and consultant laboratory for coronaviruses of the RKI in Berlin, testing was available locally by the end of February. Local testing capacity was rapidly increased. While initial test runs were performed once daily, capacity was soon expanded to three PCR runs per day, reducing the sample-to-result time to about half a day. With availability of cartridge based tests from May, the delay could be further reduced to two to three hours for a limited number of samples; thus some patients could be kept in the ED or in designated holding areas until test results were obtained. This saved the capacities of the respiratory infections ward.
Between 29 February and 17 May 2020, a total of 450 respiratory specimens were collected from patients aged under 18 years for SARS-CoV-2 RNA RT-PCR testing. These correspond to 392 different cases defined as outpatient visits and hospital admissions of a total of 346 patients. The median age of the 346 children tested was 3.5 years (IQR: 1–11 years) years, of whom 10 (3%) were aged < 1 month, 67 (19%) were aged 1–12 months, 138 (40%) were aged 1–6 years, 60 (17%) were aged 7–12 years and 71 (21%) were aged 13–18 years; and 165 (48%) were female.
In 175 (45%) out of 392 cases, symptoms suspicious of COVID-19 (any of: fever, respiratory symptoms other than rhinitis, diarrhoea, loss of smell or taste) were present. 207 (53%) cases presented without any of these typical symptoms, and in 10 (3%) cases the symptoms were unknown. Among the 175 suspected cases, SARS-CoV-2 infection was present in 7 (4%), while among the 207 cases without typical symptoms, SARS-CoV-2 was detected in 2 (1%). These latter two patients presented with orbital swelling and livid discoloration of the legs, respectively (Table 1). There were no asymptomatic cases of COVID-19 diagnosed.
For 220 (56%) of the 392 cases, SARS-CoV-2 tests were performed on or shortly before hospital admission, 94 (24%) tests were done for inpatients and 75 (19%) for outpatients; 201 (51%) tests were done in children admitted to a general paediatric department (ED or general ward including patients from neurology, gastroenterology, rheumatology and nephrology), 79 (20%) to haemato-oncology (outpatient clinic or ward), 44 (11%) to cardiology, 31 (8%) to surgery, 25 (6%) to the PICU, 5 (1%) to neonatology and 7 (2%) to other departments.
The COVID-19 epidemic in Tuebingen coincided with the end of the acute respiratory infection season. The last cases of RSV and influenza were recorded on 28 March. Until then, during the first 3 months of 2020, 82 (67%) out of 108 tested cases had symptoms of COVID-19. Among these, 12 (15%) were diagnosed with RSV, 5 (6%) with influenza, and 2 (2%) with SARS-CoV-2.
Characteristics of patients admitted with COVID-19
Between 26 March and 20 July 2020, nine patients with COVID-19 were admitted to our children’s hospital. All were admitted to the paediatric COVID 19/respiratory infections ward. Eight were diagnosed on admission and one was diagnosed prior to admission. Data on the clinical course, treatment and outcome are presented in Table 1
The presenting symptoms included fever in six patients (one developed fever later), respiratory symptoms in five patients, and gastrointestinal symptoms in two patients. One patient presented with orbital swelling and another one with livid discoloration of the legs as the initial symptom. Six patients had underlying comorbidities, of whom three had an impaired immune system due to immunosuppressive treatment (two cases) or after haematopoietic stem cell transplantation (HSCT).
Four patients required oxygen therapy. Two patients required admission to the PICU: an 18-year-old boy with hypoplastic left heart syndrome and a 16-year-old girl who had received kidney transplantation 12 years previously. The girl required invasive ventilation. Experimental treatments were used in two out of nine patients: one patient with distinct thrombocyte activation received treatment with defibrotide to prevent blood clotting. Another patient who had undergone HSCT a year before received ribavirin treatment.
All of our nine patients were discharged alive, two with mild residual symptoms. However, the 18-year-old boy died at home, 11 days after discharge. Autopsy of the brain showed cerebral vasculitis probably associated with COVID-19 [24, 25].