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      Long COVID symptoms in SARS-CoV-2-positive children aged 0–14 years and matched controls in Denmark (LongCOVIDKidsDK): a national, cross-sectional study

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          Abstract

          Background

          After the acute phase of SARS-CoV-2 infection, children can develop long COVID symptoms. We aimed to investigate the prevalence of long-lasting symptoms, the duration and intensity of symptoms, quality of life, number of sick days and absences from daycare or school, and psychological and social outcomes in children aged 0–14 years who had been infected with SARS-CoV-2 relative to controls with no history of SARS-CoV-2 infection.

          Methods

          A nationwide cross-sectional study was conducted including children with a confirmed SARS-CoV-2-positive PCR test (cases) and matched controls from Danish national registers. A survey was sent to mothers (proxy reporting) of children aged 0–14 years who had had a positive SARS-CoV-2 test between Jan 1, 2020, and July 12, 2021, and a control group matched (1:4) by age and sex. The survey included the Pediatric Quality of Life Inventory (PedsQL) and the Children's Somatic Symptoms Inventory-24 (CSSI-24) to capture current overall health and wellbeing, and ancillary questions about the 23 most common long COVID symptoms. Descriptive statistics and logistic regression analysis were used. Clinically relevant differences were defined as those with a Hedges' g score greater than 0·2. This study is registered at ClinicalTrials.gov (NCT04786353).

          Findings

          Responses to the survey were received from 10 997 (28·8%) of 38 152 cases and 33 016 (22·4%) of 147 212 controls between July 20, 2021, and Sept 15, 2021. Median age was 10·2 years (IQR 6·6–12·8) in cases and 10·6 years (6·9–12·9) in controls. 5267 (48·2%) cases and 15 777 (48·3%) controls were female, and 5658 (51·8%) cases and 16 870 (51·7%) controls were male. Cases had higher odds of reporting at least one symptom lasting more than 2 months than did controls in the 0–3 years age group (478 [40·0%] of 1194 vs 1049 [27·2%] of 3855; OR 1·78 [95% CI 1·55–2·04], p<0·0001), 4–11 years age group (1912 [38·1%] of 5023 vs 6189 [33·7%] of 18 372; 1·23 [1·15–1·31], p<0·0001), and 12–14 years age group (1313 [46·0%] of 2857 vs 4454 [41·3%] of 10 789; 1·21 [1·11–1·32], p<0·0001). Differences in CSSI-24 symptom scores between cases and controls were statistically significant but not clinically relevant. Small clinically relevant differences in PedsQL quality-of-life scores related to emotional functioning were found in favour of cases in the children aged 4–11 years (median score 80·0 [IQR 65·0–95·0]) in cases vs 75·0 [60·0–85·0] in controls; p<0·0001) and 12–14 years (90·0 [70·0–100·0] vs (85·0 [65·0–95·0], p<0·0001). PedsQL social functioning scores were also higher in cases (100·0 [90·0–100·0] than controls (95·0 [80·0–100·0]) in the 12–14 years age group (p<0·0001; Hedges g>0·2).

          Interpretation

          Compared with controls, children aged 0–14 years who had a SARS-CoV-2 infection had more prevalent long-lasting symptoms. There was a tendency towards better quality-of-life scores related to emotional and social functioning in cases than in controls in older children. The burden of symptoms among children in the control group requires attention. Long COVID must be recognised and multi-disciplinary long COVID clinics for children might be beneficial.

          Funding

          A P Møller and Chastine Mc-Kinney Møller Foundation.

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          Most cited references25

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          Distribution Theory for Glass's Estimator of Effect size and Related Estimators

          L. Hedges (1981)
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            WHO Child Growth Standards based on length/height, weight and age

            To describe the methods used to construct the WHO Child Growth Standards based on length/height, weight and age, and to present resulting growth charts.
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              Is Open Access

              Illness duration and symptom profile in symptomatic UK school-aged children tested for SARS-CoV-2

              Summary Background In children, SARS-CoV-2 infection is usually asymptomatic or causes a mild illness of short duration. Persistent illness has been reported; however, its prevalence and characteristics are unclear. We aimed to determine illness duration and characteristics in symptomatic UK school-aged children tested for SARS-CoV-2 using data from the COVID Symptom Study, one of the largest UK citizen participatory epidemiological studies to date. Methods In this prospective cohort study, data from UK school-aged children (age 5–17 years) were reported by an adult proxy. Participants were voluntary, and used a mobile application (app) launched jointly by Zoe Limited and King's College London. Illness duration and symptom prevalence, duration, and burden were analysed for children testing positive for SARS-CoV-2 for whom illness duration could be determined, and were assessed overall and for younger (age 5–11 years) and older (age 12–17 years) groups. Children with longer than 1 week between symptomatic reports on the app were excluded from analysis. Data from symptomatic children testing negative for SARS-CoV-2, matched 1:1 for age, gender, and week of testing, were also assessed. Findings 258 790 children aged 5–17 years were reported by an adult proxy between March 24, 2020, and Feb 22, 2021, of whom 75 529 had valid test results for SARS-CoV-2. 1734 children (588 younger and 1146 older children) had a positive SARS-CoV-2 test result and calculable illness duration within the study timeframe (illness onset between Sept 1, 2020, and Jan 24, 2021). The most common symptoms were headache (1079 [62·2%] of 1734 children), and fatigue (954 [55·0%] of 1734 children). Median illness duration was 6 days (IQR 3–11) versus 3 days (2–7) in children testing negative, and was positively associated with age (Spearman's rank-order r s 0·19, p<0·0001). Median illness duration was longer for older children (7 days, IQR 3–12) than younger children (5 days, 2–9). 77 (4·4%) of 1734 children had illness duration of at least 28 days, more commonly in older than younger children (59 [5·1%] of 1146 older children vs 18 [3·1%] of 588 younger children; p=0·046). The commonest symptoms experienced by these children during the first 4 weeks of illness were fatigue (65 [84·4%] of 77), headache (60 [77·9%] of 77), and anosmia (60 [77·9%] of 77); however, after day 28 the symptom burden was low (median 2 symptoms, IQR 1–4) compared with the first week of illness (median 6 symptoms, 4–8). Only 25 (1·8%) of 1379 children experienced symptoms for at least 56 days. Few children (15 children, 0·9%) in the negatively tested cohort had symptoms for at least 28 days; however, these children experienced greater symptom burden throughout their illness (9 symptoms, IQR 7·7–11·0 vs 8, 6–9) and after day 28 (5 symptoms, IQR 1·5–6·5 vs 2, 1–4) than did children who tested positive for SARS-CoV-2. Interpretation Although COVID-19 in children is usually of short duration with low symptom burden, some children with COVID-19 experience prolonged illness duration. Reassuringly, symptom burden in these children did not increase with time, and most recovered by day 56. Some children who tested negative for SARS-CoV-2 also had persistent and burdensome illness. A holistic approach for all children with persistent illness during the pandemic is appropriate. Funding Zoe Limited, UK Government Department of Health and Social Care, Wellcome Trust, UK Engineering and Physical Sciences Research Council, UK Research and Innovation London Medical Imaging and Artificial Intelligence Centre for Value Based Healthcare, UK National Institute for Health Research, UK Medical Research Council, British Heart Foundation, and Alzheimer's Society.
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                Author and article information

                Journal
                Lancet Child Adolesc Health
                Lancet Child Adolesc Health
                The Lancet. Child & Adolescent Health
                Elsevier Ltd.
                2352-4642
                2352-4650
                23 June 2022
                23 June 2022
                Affiliations
                [a ]Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
                [b ]Department of Paediatrics and Adolescents Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
                [c ]Department of Infectious Disease, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
                [d ]Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
                [e ]The National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark
                Author notes
                [* ]Correspondence to: Prof Selina Kikkenborg Berg, Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark
                Article
                S2352-4642(22)00154-7
                10.1016/S2352-4642(22)00154-7
                9221683
                35752194
                7c8e2181-4f46-4e75-8f60-ff09cf8412e7
                © 2022 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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