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      Children with COVID-19 at a specialist centre: initial experience and outcome

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          Abstract

          The 2019 novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, characterised by potentially severe respiratory and gastrointestinal symptoms, in humans. 1 As of late May, 2020, there were around 5 million confirmed cases of COVID-19 and more than 300 000 associated deaths globally. 1 COVID-19 can affect children, but it appears to be associated with fewer symptoms and less severe disease compared with adults, with correspondingly lower case-fatality rates. 2 In the UK, Public Health England has outlined a shielding strategy designed to protect those extremely vulnerable to SARS-CoV-2 infection,3, 4 such as individuals who are immunocompromised. We examined a cohort of paediatric patients, presenting to Great Ormond Street Hospital, London, UK (a specialist children's hospital), with suspected COVID-19 to document their clinical characteristics and outcomes with regard to the presence of underlying medical conditions associated with vulnerability. We retrospectively used routinely collected deidentified hospital data within a secure digital research environment (REC approval 17/LO/0008) from children presenting to Great Ormond Street Hospital, with suspected COVID-19 between March 1 and May 15, 2020. COVID-19 positive cases were those with clinical features of COVID-19 and a positive PCR-test for SARS-CoV-2 (either directly or positive familial SARS-CoV-2 testing). Patients were classified regarding vulnerability group using NHS Digital methodology. 4 There were 65 COVID-19 postive cases (median age 9 years [IQR 0·9–14]) during the study (appendix), of whom 31 (48%) were classed as vulnerable. The most common provisional diagnosis codes for the group were sepsis, fever, and pneumonia. Only one patient who tested positive for SARS-CoV-2 died because of an underlying medical condition and another infection not thought to be related to SARS-CoV-2. 29 (45%) patients required admission to the intensive care unit. Of whom, 14 (48%) were classed as vulnerable. The length of stay in the intensive care unit for all patients was 4 days (2·4–10·6). Compared with patients classed as non-vulnerable, those classed as vulnerable had a significantly longer stay of 11 days (3·7–15·1; Mann-Whitney U test p<0·001). Of the 29 patients admitted to the intensive care unit, 18 (62%) required mechanical ventilation, of whom ten (56%) were classed as vulnerable (p=0·53). Overall hospital stay was also significantly shorter in the non-vulnerable group (3·9 days [2·5–15·7]) than in the vulnerable group (16·2 days [3·8–20·8]; p<0·001). As of May 15, 2020, nine patients (14%) remained in hospital, three of whom (33%) were classed as vulnerable (p=0·35). During the study, with a daily average of 326 inpatients, on average ten were positive for SARS-CoV-2 at any time, representing around 3% of the hospital inpatient population, much lower than the estimated 25% COVID-19-positive population reported across adult London trusts. 5 These data show the characteristics and outcomes of children presenting to a specialist children's hospital with clinical features of COVID-19 disease and positive testing, and confirm that some children with SARS-CoV-2 might have severe disease with requirement for intensive care admission. Of note, the reported cohort of patients are highly preselected, both for children with severe disease and for those with underlying medical conditions, and therefore the findings are not applicable to the general paediatric population. Stewart and colleagues 6 recently reported specific renal features in a case series of 52 children with COVID-19 referred to our centre, 35 of whom are also included in the present overall cohort. Previous data from general centres suggest that less than 1% of COVID-19 admissions are children younger than 18 years and data from multiple North American hospitals reported few paediatric patients with COVID-19 per intensive care unit.7, 8 As such, the present cohort disproportionately represents those with complex underlying medical conditions, consistent with the fact that around three quarters of inpatients registered with the hospital in 2019 would be considered as vulnerable according to COVID-19 guidance. 4 This is not unexpected because the hospital represents a centre for paediatric transplantation, genetic diseases (such as congenital immunodeficiency), and paediatric malignancy. Furthermore, in children with confirmed COVID-19, the proportion of patients with underlying vulnerable conditions requiring admission to an intensive care unit for mechanical ventilation were not significantly different to those classed as non-vulnerable. Although the possible effects of lockdown and shielding remain undetermined, given that this series includes cases from before and during lockdown (since March 23, 2020), these data raise the possibility that underlying medical conditions that place children at increased risk of COVID-19 disease or complications might differ from adults. This is consistent with a study reporting no mortality in a multicentre cohort of patients with cystic fibrosis affected by COVID-19, 9 and another using a renal registry, suggesting that children receiving immunosuppressive treatment appear to have a mild COVID-19 clinical course. 10 Susceptibility for COVID-19 in vulnerable groups might therefore be both disease-specific and related to patient age. In addition to the typical features of COVID-19 disease described in adults, although most children who are infected appear to have mild disease, 2 some might have an unusual associated systemic inflammatory condition: paediatric inflammatory multisystem syndrome temporally related to SARS-CoV-2 infection (PIMS-TS). 11 The criteria for the definitive diagnosis of PIMS-TS are evolving, and it remains uncertain whether any of the current patients with COVID could represent such cases, and studies are underway examining the PIMS-TS phenomenon. Limitations of these data include the retrospective nature of using routine data, absence of a matched control group, and the highly preselected population from a specialist children's hospital, which is not representative of the paediatric population as a whole, although these data do provide information regarding this potentially high-risk group. It should also be noted that since vulnerable children might be shielded, the pattern of presentation reported might not be representative of a non-shielded situation, and additional epidemiological studies are required.

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          Most cited references6

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          Clinical Characteristics of Coronavirus Disease 2019 in China

          Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
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            Characteristics and Outcomes of Children With Coronavirus Disease 2019 (COVID-19) Infection Admitted to US and Canadian Pediatric Intensive Care Units

            The recent and ongoing coronavirus disease 2019 (COVID-19) pandemic has taken an unprecedented toll on adults critically ill with COVID-19 infection. While there is evidence that the burden of COVID-19 infection in hospitalized children is lesser than in their adult counterparts, to date, there are only limited reports describing COVID-19 in pediatric intensive care units (PICUs).
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              Children with Covid-19 in Pediatric Emergency Departments in Italy

              To the Editor: On February 20, 2020, the incidence of Covid-19 began to rapidly escalate in Italy. By March 25, Italy had the second highest number of Covid-19 infections worldwide and the greatest number of deaths. 1 Children younger than 18 years of age who had Covid-19 composed only 1% of the total number of patients; 11% of these children were hospitalized, and none died. 2 The Coronavirus Infection in Pediatric Emergency Departments (CONFIDENCE) study involved a cohort of 100 Italian children younger than 18 years of age with Covid-19 confirmed by reverse-transcriptase–polymerase-chain-reaction testing of nasal or nasopharyngeal swabs who were assessed between March 3 and March 27 in 17 pediatric emergency departments. Here, we describe the results of the CONFIDENCE study and compare them with those from three cohorts in previously published analyses. 3-5 The median age of the children was 3.3 years (Table 1). Exposure to SARS-CoV-2 from an unknown source or from a source outside the child’s family accounted for 55% of the cases of infection. A total of 12% of the children appeared ill, and 54% had a temperature of at least 37.6°C. Common symptoms were cough (in 44% of the patients) and no feeding or difficulty feeding (in 23%); the latter symptom occurred more often in children younger than 21 months of age. Fever, cough, or shortness of breath occurred in 28 of 54 of febrile patients (52%) (Table S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). A total of 4% of the children had oxygen saturation values (as measured by pulse oximetry) of less than 95%; all these patients also had imaging evidence of lung involvement. Of the 9 patients who received respiratory support (Table S2), 6 had coexisting conditions. Laboratory and imaging findings are provided in Tables S3 and S4. According to the categories described by Dong et al., 4 21% of the patients were asymptomatic, 58% had mild disease, 19% had moderate disease, 1% had severe disease, and 1% were in critical condition (Table S5). Most of the infants presented with mild disease. Severe and critical cases were diagnosed in patients with coexisting conditions. No deaths were reported. A total of 38% of the patients were admitted to the hospital because of symptoms, irrespective of the severity of disease (Table 1). 4 Among our patients, the incidence of transmission through apparent exposure to a family cluster was lower than that in other cohorts, possibly because of the late lockdown in Italy. As compared with the other cohorts, fewer patients in our cohort had moderate-to-severe disease, possibly because chest radiography was predominantly used and chest computed tomography was rarely used. Thus, fewer cases of diagnosed (subclinical) pneumonia may have been identified. Bedside lung ultrasonography by experienced sonographers was performed in only 10% of the patients, 90% of whom received a diagnosis of lung interstitial syndrome without further radiographic imaging.
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                Author and article information

                Contributors
                Journal
                Lancet Child Adolesc Health
                Lancet Child Adolesc Health
                The Lancet. Child & Adolescent Health
                Elsevier Ltd.
                2352-4642
                2352-4650
                23 June 2020
                23 June 2020
                Affiliations
                [a ]Digital Research and Informatics Unit, Great Ormond Street Hospital and Great Ormond Street Institute of Child Health and NIHR GOSH Biomedical Research Centre, London WC1N 3JH, UK
                [b ]Institute of Cardiovascular Science, University College London, United Kingdom
                [c ]Faculty of Population Health Sciences, University College London, United Kingdom
                [d ]Institute of Health Informatics UCL and NIHR UCLH Biomedical Research Centre, London UK
                Article
                S2352-4642(20)30204-2
                10.1016/S2352-4642(20)30204-2
                7308787
                32585186
                2f1be7d4-3e08-4c18-b732-40275ea4db2c
                © 2020 Elsevier Ltd. All rights reserved.

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

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