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      SARS-CoV-2 Clinical Syndromes and Predictors of Disease Severity in Hospitalized Children and Youth

      research-article
      , MD 1 , # , , , MD, PhD 2 , , , MD 1 , , MS 1 , , PhD 1 , , ScD 1 , , MBBS 3 , , MD 4 , , MD 5 , , MD 5 , , MD 4 , , MD 6 , , BA 1 , , MD 5 , , MD 2 , , MD 5 , , MD 3 , , MD 1 , , MD 7 , , MD 8 , , DO 2 , , MD 5 , , MD 7 , , MD 4 , , MD 5 , , MD 8 , , MD 6 , , MD 2 , , MD 6 , , MD 1 , , MD 7 , , MD 2 , , MD, MPH 1 , , MD 1 , Tri-State Pediatric COVID-19 Research Consortium Authors
      The Journal of Pediatrics
      Elsevier Inc.
      COVID-19, Biomarkers, MIS-C, multisystem inflammatory syndrome in children, COVID-19, coronavirus disease 2019, SES, socioeconomic status, CDC, Centers for Disease Control and Prevention, ICU, intensive care unit, BMI, body mass index, aOR, adjusted odds ratio, CRP, C-reactive protein, ALC, absolute lymphocyte count, BNP, B-type natriuretic protein

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          Abstract

          Objective

          To characterize the demographic and clinical features of pediatric SARS-CoV-2 syndromes and identify admission variables predictive of disease severity.

          Study design

          We conducted a multicenter, retrospective and prospective study of pediatric patients hospitalized with acute SARS-CoV-2 infections and multisystem inflammatory syndrome in children (MIS-C) at eight sites in New York, New Jersey, and Connecticut.

          Results

          We identified 281 hospitalized patients with SARS-CoV-2 infections and divided them into three groups based on clinical features. Overall, 143 (51%) had respiratory disease, 69 (25%) had MIS-C, and 69 (25%) had other manifestations including gastrointestinal illness or fever. Patients with MIS-C were more likely to identify as non-Hispanic black compared with patients with respiratory disease (35% versus 18%, P=.02). Seven patients (2%) died and 114 (41%) were admitted to the ICU. In multivariable analyses, obesity (OR=3.39, 95% CI:1.26-9.10, P=.02) and hypoxia on admission (OR=4.01; 95% CI:1.14-14.15; P=.03) were predictive of severe respiratory disease. Lower absolute lymphocyte count (OR=8.33 per unit decrease in 10 9 cells/L, 95% CI:2.32-33.33, P=.001) and higher C-reactive protein (OR=1.06 per unit increase in mg/dL, 95% CI:1.01-1.12, P=.017) were predictive of severe MIS-C. Race/ethnicity or socioeconomic status were not predictive of disease severity.

          Conclusions

          We identified variables at the time of hospitalization that may help predict the development of severe SARS-CoV-2 disease manifestations in children and youth. These variables may have implications for future prognostic tools that inform hospital admission and clinical management.

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          Most cited references36

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          Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

          Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
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            Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area

            There is limited information describing the presenting characteristics and outcomes of US patients requiring hospitalization for coronavirus disease 2019 (COVID-19).
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              Remdesivir for the Treatment of Covid-19 — Final Report

              Abstract Background Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious. Methods We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. Results A total of 1063 patients underwent randomization. The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomization (21.1%) and 141 of the 522 patients in the placebo group who underwent randomization (27.0%). Conclusions Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.)
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                Author and article information

                Journal
                J Pediatr
                J Pediatr
                The Journal of Pediatrics
                Elsevier Inc.
                0022-3476
                1097-6833
                14 November 2020
                14 November 2020
                Affiliations
                [1 ]Department of Pediatrics, Albert Einstein College of Medicine, Children’s Hospital at Montefiore, Bronx, New York
                [2 ]Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut
                [3 ]Department of Pediatrics, Kings County Hospital Center, Brooklyn, New York
                [4 ]Department of Pediatrics, Maimonides Children’s Hospital, Brooklyn, New York
                [5 ]Department of Pediatrics, Joseph M. Sanzari Children’s Hospital, Hackensack, New Jersey
                [6 ]Department of Pediatrics, K. Hovnanian Children’s Hospital, Neptune City, New Jersey
                [7 ]Department of Pediatrics, SUNY Downstate Medical Center University Hospital, Brooklyn, New York
                [8 ]Department of Pediatrics, Stony Brook University Renaissance Hospital, Stony Brook, New York
                Author notes
                [# ]Corresponding Author: Danielle M. Fernandes, MD, Department of Pediatrics, The Children’s Hospital at Montefiore, 3411 Wayne Avenue, Room 851, Bronx NY, 10467, Phone: 718-741-2390, Fax: 718-920-6506,
                [∗]

                Contributed equally

                Article
                S0022-3476(20)31393-7
                10.1016/j.jpeds.2020.11.016
                7666535
                33197493
                9894b990-053e-4688-ac0c-d0a1a5a1a54c
                © 2020 Elsevier Inc. 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.

                History
                : 10 October 2020
                : 2 November 2020
                : 10 November 2020
                Categories
                Original Articles

                Pediatrics
                covid-19,biomarkers,mis-c, multisystem inflammatory syndrome in children,covid-19, coronavirus disease 2019,ses, socioeconomic status,cdc, centers for disease control and prevention,icu, intensive care unit,bmi, body mass index,aor, adjusted odds ratio,crp, c-reactive protein,alc, absolute lymphocyte count,bnp, b-type natriuretic protein

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