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      Convalescent plasma for pediatric patients with SARS-CoV-2-associated acute respiratory distress syndrome

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      Pediatric blood & cancer
      convalescent plasma, COVID-19, pediatrics, SARS-CoV-2

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          Abstract

          There are no proven safe and effective therapies for children who develop life-threatening complications of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Convalescent plasma (CP) has demonstrated potential benefit in adults with SARS-CoV-2, but has theoretical risks.We present the first report of CP in children with life-threatening coronavirus disease 2019 (COVID-19), providing data on four pediatric patients with acute respiratory distress syndrome. We measured donor antibody levels and recipient antibody response prior to and following CP infusion. Infusion of CP was not associated with antibody-dependent enhancement (ADE) and did not suppress endogenous antibody response. We found CP was safe and possibly efficacious. Randomized pediatric trials are needed.

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Epidemiological Characteristics of 2143 Pediatric Patients With 2019 Coronavirus Disease in China

            To identify the epidemiological characteristics and transmission patterns of pediatric patients with the 2019 novel coronavirus disease (COVID-19) in China.
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              Treatment of 5 Critically Ill Patients With COVID-19 With Convalescent Plasma

              Could administration of convalescent plasma transfusion be beneficial in the treatment of critically ill patients with coronavirus disease 2019 (COVID-19)? In this uncontrolled case series of 5 critically ill patients with COVID-19 and acute respiratory distress syndrome (ARDS), administration of convalescent plasma containing neutralizing antibody was followed by an improvement in clinical status. These preliminary findings raise the possibility that convalescent plasma transfusion may be helpful in the treatment of critically ill patients with COVID-19 and ARDS, but this approach requires evaluation in randomized clinical trials. Coronavirus disease 2019 (COVID-19) is a pandemic with no specific therapeutic agents and substantial mortality. It is critical to find new treatments. To determine whether convalescent plasma transfusion may be beneficial in the treatment of critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Case series of 5 critically ill patients with laboratory-confirmed COVID-19 and acute respiratory distress syndrome (ARDS) who met the following criteria: severe pneumonia with rapid progression and continuously high viral load despite antiviral treatment; P ao 2 /F io 2 <300; and mechanical ventilation. All 5 were treated with convalescent plasma transfusion. The study was conducted at the infectious disease department, Shenzhen Third People's Hospital in Shenzhen, China, from January 20, 2020, to March 25, 2020; final date of follow-up was March 25, 2020. Clinical outcomes were compared before and after convalescent plasma transfusion. Patients received transfusion with convalescent plasma with a SARS-CoV-2–specific antibody (IgG) binding titer greater than 1:1000 (end point dilution titer, by enzyme-linked immunosorbent assay [ELISA]) and a neutralization titer greater than 40 (end point dilution titer) that had been obtained from 5 patients who recovered from COVID-19. Convalescent plasma was administered between 10 and 22 days after admission. Changes of body temperature, Sequential Organ Failure Assessment (SOFA) score (range 0-24, with higher scores indicating more severe illness), P ao 2 /F io 2 , viral load, serum antibody titer, routine blood biochemical index, ARDS, and ventilatory and extracorporeal membrane oxygenation (ECMO) supports before and after convalescent plasma transfusion. All 5 patients (age range, 36-65 years; 2 women) were receiving mechanical ventilation at the time of treatment and all had received antiviral agents and methylprednisolone. Following plasma transfusion, body temperature normalized within 3 days in 4 of 5 patients, the SOFA score decreased, and P ao 2 /F io 2 increased within 12 days (range, 172-276 before and 284-366 after). Viral loads also decreased and became negative within 12 days after the transfusion, and SARS-CoV-2–specific ELISA and neutralizing antibody titers increased following the transfusion (range, 40-60 before and 80-320 on day 7). ARDS resolved in 4 patients at 12 days after transfusion, and 3 patients were weaned from mechanical ventilation within 2 weeks of treatment. Of the 5 patients, 3 have been discharged from the hospital (length of stay: 53, 51, and 55 days), and 2 are in stable condition at 37 days after transfusion. In this preliminary uncontrolled case series of 5 critically ill patients with COVID-19 and ARDS, administration of convalescent plasma containing neutralizing antibody was followed by improvement in their clinical status. The limited sample size and study design preclude a definitive statement about the potential effectiveness of this treatment, and these observations require evaluation in clinical trials. This case series describes clinical outcomes in 5 Chinese patients with laboratory-confirmed COVID-19, ARDS, and high viral loads despite antiviral treatment who were given human plasma with SARS-CoV-2 antibodies obtained from previously infected and recovered patients.
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                Author and article information

                Journal
                101186624
                30479
                Pediatr Blood Cancer
                Pediatr Blood Cancer
                Pediatric blood & cancer
                1545-5009
                1545-5017
                7 December 2020
                04 September 2020
                November 2020
                01 November 2021
                : 67
                : 11
                : e28693
                Affiliations
                [1 ]Immune Dysregulation Frontier Program, Department of Pediatrics, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
                [2 ]Division of Oncology, Department of Pediatrics, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
                [3 ]Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
                [4 ]Division of Rheumatology, Department of Pediatrics, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
                [5 ]Division of Infectious Diseases, Department of Pediatrics, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
                [6 ]Division of Allergy and Immunology, Department of Pediatrics, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
                [7 ]Division of Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
                [8 ]Division of Hematology, Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
                [9 ]American Red Cross, Washington, District of Columbia
                [10 ]Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania
                Author notes
                Correspondence David T. Teachey, Department of Pediatrics, Division of Oncology, The Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, 3008 CTRB, 3501 Civic Center Blvd, Philadelphia, PA 19104. teacheyd@ 123456email.chop.edu

                AUTHOR CONTRIBUTIONS

                Caroline Diorio and Elizabeth M. Anderson equally contributed to this work and are senior first authors. Edward M. Behrens, David T. Teachey, and Hamid Bassiri equally contributed to this work and are co-senior authors. Caroline Diorio, Elizabeth M. Anderson, Sarah E. Henrickson, Laura A. Vella, Kevin O. McNerney, Julie C. Chase, Scott E. Hensley, Edward M. Behrens, Hamid Bassiri, and David T. Teachey designed the study, analyzed data, and wrote the manuscript; Kathleen Chiotos, Michele P. Lambert, Allison M. Blatz, Julie C. Fitzgerald, Todd J. Kilbaugh, Audrey R. Odom John, Kathleen E. Sullivan, David Friedman, Deborah A. Sesok-Pizzini, Margaret R.Tartaglione, Danielle Zambrano, Meghan Martin, Jessica H. Lee, and Pampee Young contributed to the study design, analyzed data, and helped write the manuscript. Elizabeth M. Anderson, Madison E. Weirick, Sigrid Gouma, Eileen C. Goodwin, Marcus J. Bolton, Claudia P. Arevalo performed experiments, provided data, and edited manuscript. Caroline Diorio, Julie C. Chase, and Kevin O. McNerney enrolled subjects. Pampee Young, Deborah A. Sesok-Pizzini, and David Friedman also provided specimens. All authors contributed intellectually and reviewed and revised the manuscript.

                Author information
                http://orcid.org/0000-0002-1168-4773
                http://orcid.org/0000-0002-4359-3569
                http://orcid.org/0000-0003-2525-1212
                http://orcid.org/0000-0003-0439-402X
                http://orcid.org/0000-0001-7373-8987
                Article
                NIHMS1652161
                10.1002/pbc.28693
                7734626
                32885904
                a3e32a8a-982a-4a8b-836c-b6a2d9c7442e

                This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. http://creativecommons.org/licenses/by/4.0/

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                Article

                Pediatrics
                convalescent plasma,covid-19,pediatrics,sars-cov-2
                Pediatrics
                convalescent plasma, covid-19, pediatrics, sars-cov-2

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