COVID-19 Publications

24

Nov, 2020

Kinetics and seroprevalence of SARS-CoV-2 antibodies in children

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Authors: Cathal Roarty, Claire Tonry, Lisa McFetridge, Hannah Mitcheòò, Chris Watson, Thomas Waterfeild, on behalf of the Covid Warriors research team

Published in: The Lancet Infectious Diseases

Abstract: To the best of our knowledge, no longitudinal study has reported the kinetics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody responses in children. Here we report the results of the second round of antibody testing in children from a prospective multicentre cohort study in the UK. The protocol and initial results are available elsewhere.

Recruitment took place between April 16, and July 3, 2020, at five UK sites (Belfast, Cardiff, Glasgow, London, and Manchester) and included healthy children aged 2–15 years. Follow-up visits at all five UK sites took place between June 26, and Aug 15, 2020.

Of the 992 participants in the first round, 849 (86%) returned. Seroprevalence was measured with the Elecsys Anti-SARS-CoV-2 Total Antibody assay (Roche, Basel, Switzerland) and the LIAISON SARS-CoV-2 S1/S2 IgG assay (DiaSorin, Saluggia, Italy). The median time between initial and follow-up visits was 62 days (IQR 52–70; range 43–81). 65 (7·66%, 95% CI 6·05–9·64) of 849 tests were reactive based on the manufacturers’ suggested cutoffs. This proportion was not substantially different to the seroprevalence (6·9% 95% CI 5·4 to 8·6; 68 of 992) reported during recruitment. The median age of participants with reactive antibody tests during the second round was 10 years (IQR 7–14; range 3–16). As with the baseline results, there was variation in seroprevalence between sites.
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31

Aug, 2020

COVID-19 Pandemic: Perspective of an Italian Tertiary Care Pediatric Center

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Abstract Since February 2020, Italy has been faced with the dramatic spread of novel Coronavirus SARS-CoV-2. This impetuous pandemic infection forced many hospitals to reorganize their healthcare systems. Predicting a rapid spread of the SARS-CoV-2 virus within our region, the Department for Women’s and Children’s Health promptly decided (i) to revise the distribution of the clinical areas in order to create both designated COVID-19 and COVID-19-free areas with their own access, (ii) to reinforce infection prevention control (IPC) measures for all healthcare workers and administrative staff and (iii) to adopt the new “double-gate approach”: a phone call pre-triage and nasopharyngeal swab for SARS-CoV-2 detection before the admission of all patients and caregivers. Between 21 February 2020 till 04 May 2020, only seven physicians, two nurses and two of the administrative staff resulted positive, all during the first week of March. No other cases of intra-department infection were documented among the healthcare workers since all the preventive procedures described above were implemented. It is predicted that similar situations can happen again in the future, and thus, it is necessary to be more prepared to deal with them than we were at the beginning of this COVID-19 pandemic.

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21

Aug, 2020

Pediatric transplantation in Europe during the COVID-19 pandemic: early impact on activity and healthcare

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Abstract The current pandemic SARS-CoV-2 virus has required an unusual allocation of resources that can negatively impact of chronically ill patients and high-complexity procedures. Across the European reference network on pediatric transplantation (ERN-TransplantChild) we conducted a survey to investigate the impact of the COVID-19 outbreak on pediatric transplant activity and healthcare practices in both solid organ transplantation (SOT) and hematopoietic stem cell (HSCT) transplantation. The replies of 30 professionals from 18 centers in Europe were collected. Twelve of 18 centers (67%) showed a reduction in their usual transplant activity. Additionally, outpatient visits have been modified, restricted to selected ones and to the use of telemedicine tools has increased. Additionally, a total of 14 COVID-19 pediatric transplanted patients were identified at the time of the survey, including eight transplant recipients and six candidates for transplantation. Only two moderate-severe cases were reported, both in HSCT setting. These survey results demonstrate the limitations in healthcare resources for pediatric transplantation patients during early stages of this pandemic. COVID-19 disease is a major worldwide challenge for the field of pediatric transplantation, where there will be a need for systematic data collection, encouraging regular discussions to address the long-term consequences for pediatric transplantation candidates, recipients and their families.

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21

Jul, 2020

Co-infection and other clinical characteristics of COVID-19 in children

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Background and Objectives Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly identified pathogen that mainly spreads by droplets. Most published studies have been focused on adult patients with coronavirus disease 2019 (COVID-19), but data concerning pediatric patients are limited. In this study, we aimed to determine epidemiological characteristics and clinical features of pediatric patients with COVID-19.

Methods We reviewed and analyzed data on pediatric patients with laboratory-confirmed COVID-19, including basic information, epidemiological history, clinical manifestations, laboratory and radiologic findings, treatment, outcome, and follow-up results.

Results A total of 74 pediatric patients with COVID-19 were included in this study. Of the 68 case patients whose epidemiological data were complete, 65 (65 of 68; 95.59%) were household contacts of adults. Cough (32.43%) and fever (27.03%) were the predominant symptoms of 44 (59.46%) symptomatic patients at onset of the illness. Abnormalities in leukocyte count were found in 23 (31.08%) children, and 10 (13.51%) children presented with abnormal lymphocyte count. Of the 34 (45.95%) patients who had nucleic acid testing results for common respiratory pathogens, 19 (51.35%) showed coinfection with other pathogens other than SARS-CoV-2. Ten (13.51%) children had real-time reverse transcription polymerase chain reaction analysis for fecal specimens, and 8 of them showed prolonged existence of SARS-CoV-2 RNA.

Conclusions Pediatric patients with COVID-19 presented with distinct epidemiological, clinical, and radiologic characteristics from adult patients. Nearly one-half of the infected children had coinfection with other common respiratory pathogens. It is not uncommon for pediatric patients to have prolonged fecal shedding of SARS-CoV-2 RNA during the convalescent phase.

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21

Jul, 2020

Lung ultrasound in children with COVID-19

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Abstract The novel coronavirus disease 2019 (COVID-19) is rapidly spreading all around the world, affecting both adults and children. Recently, the clinical and radiographic characteristics of children infected have been described. Although lung ultrasound (LUS) is recognized as a valid imaging technique for the diagnosis and follow-up of pneumonia in pediatric age, no data are currently available about LUS use in children with COVID-19. Considering the well-known advantages of point-of-care ultrasound, including the possibility of reducing the patient’s movement across the hospital department, we investigated LUS findings in children infected with severe acute respiratory syndrome–coronavirus.

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21

Jun, 2020

A multicenter national survey of children with SARS-CoV-2 infection admitted to Spanish Pediatric Intensive Care Units

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The pandemic outbreak of SARS-CoV-2 is the greatest challenge ever faced by intensive care units throughout the globe. Most studies report a low incidence and little need for hospitalization in children. Nevertheless, up to 10% of hospitalized children under 1 year of age require PICU admission. The first cases of SARS-CoV-2 infection in Spain were identified in February. Te number of cases increased significantly during the following weeks . Although children appear to be relatively spared of severe disease, the Spanish Ministry of Health reported over 200 children requiring admission to a pediatric ward, 10% of which were admitted to a PICU. We present the preliminary results of a national multicenter registry of SARS-CoV-2 infection in children requiring intensive care.

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21

Jun, 2020

Clinical characteristics of acute respiratory syndrome with SARS-CoV-2 infection in children in South China

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Background A retrospective study was conducted to summarize the clinical information of childhood infections during the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) epidemic.

Methods Children with SARS‐CoV‐2 infection in 11 hospitals from three provinces of South China were included in the study. Clinical information was collected and compared with children and adults infected by SARS‐CoV‐2 in Wuhan.

Results In total, 52 children were enrolled, including 28 boys. The median age was 9 years (interquartile range [IQR], 4‐12); 44.2% cases were of clustered occurrences, 40.4% patients had fever, 48.1% had cough, and 46.2% had a high lymphocyte count. No abnormalities were found in the liver and kidney function. Also, 82.7% of patients received antiviral therapy, but such therapy did not shorten the time to virus negativity or hospital stay (P = .082). The time to virus negativity was 12.0 days (IQR, 8.0‐16.8) and hospital stay was 14.5 days (IQR, 10.3‐17.9). Compared with reports in Wuhan, there were more acute upper respiratory tract infection (AURTI) and fewer pneumonia cases (P = .000). Compared with the non‐ICU adult COVID‐19 in Wuhan, these children’s diseases were relatively mild, with fewer complications.

Conclusions Children with SARS‐CoV‐2 infection had a mild fever, lymphocyte elevation was more common than reduction, and antiviral treatment had no obvious effect. The overall clinical manifestations were mild, and the prognosis was good.
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21

Jun, 2020

COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study

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Background To date, few data on paediatric COVID-19 have been published, and most reports originate from China. This study aimed to capture key data on children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic.

Methods This multicentre cohort study involved 82 participating health-care institutions across 25 European countries, using a well established research network—the Paediatric Tuberculosis Network European Trials Group (ptbnet)—that mainly comprises paediatric infectious diseases specialists and paediatric pulmonologists. We included all individuals aged 18 years or younger with confirmed SARS-CoV-2 infection, detected at any anatomical site by RTPCR, between April 1 and April 24, 2020, during the initial peak of the European COVID-19 pandemic. We explored factors associated with need for intensive care unit (ICU) admission and initiation of drug treatment for COVID-19 using univariable analysis, and applied multivariable logistic regression with backwards stepwise analysis to further explore those factors significantly associated with ICU admission.

Findings 582 individuals with PCR-confirmed SARS-CoV-2 infection were included, with a median age of 5·0 years (IQR 0·5–12·0) and a sex ratio of 1·15 males per female. 145 (25%) had pre-existing medical conditions. 363 (62%) individuals were admitted to hospital. 48 (8%) individuals required ICU admission, 25 (4%) mechanical ventilation (median duration 7 days, IQR 2–11, range 1–34), 19 (3%) inotropic support, and one (<1%) extracorporeal membrane oxygenation. Significant risk factors for requiring ICU admission in multivariable analyses were being younger than 1 month (odds ratio 5·06, 95% CI 1·72–14·87; p=0·0035), male sex (2·12, 1·06–4·21; p=0·033), pre-existing medical conditions (3·27, 1·67–6·42; p=0·0015), and presence of lower respiratory tract infection signs or symptoms at presentation (10·46, 5·16–21·23; p<0·0001). The most frequently used drug with antiviral activity was hydroxychloroquine (40 [7%] patients), followed by remdesivir (17 [3%] patients), lopinavir–ritonavir (six [1%] patients), and oseltamivir (three [1%] patients). Immunomodulatory medication used included corticosteroids (22 [4%] patients), intravenous immunoglobulin (seven [1%] patients), tocilizumab (four [1%] patients), anakinra (three [1%] patients), and siltuximab (one [<1%] patient). Four children died (case-fatality rate 0·69%, 95% CI 0·20–1·82); at study end, the remaining 578 were alive and only 25 (4%) were still symptomatic or requiring respiratory support.

Interpretation COVID-19 is generally a mild disease in children, including infants. However, a small proportion develop severe disease requiring ICU admission and prolonged ventilation, although fatal outcome is overall rare. The data also reflect the current uncertainties regarding specific treatment options, highlighting that additional data on antiviral and immunomodulatory drugs are urgently needed.

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21

Jun, 2020

Identification of symptoms prognostic of COVID-19 severity: multivariate data analysis of a case series in Henan province

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Background The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease (COVID-19), has been declared a global pandemic. Identifying individuals whose infection can potentially become severe is critical to control the case fatality rate of COVID-19. However, knowledge of symptoms that are prognostic of COVID-19 severity is lacking.

Objective The objective of our study was to identify symptoms prognostic of COVID-19 infection severity.

Methods We analyzed documented symptoms, including fever, cough, fatigue, expectoration, sore throat, chest distress, headache, diarrhea, rhinorrhea, stuffed nose, nausea, vomiting, muscle or joint ache, shortness of breath, and their associations with disease severity using a case series, including 655 confirmed cases from January 23 to February 5, 2020 in Henan Province, China. We also analyzed the influence of individual characteristics, including age, gender, and comorbidities, on symptoms with prognostic value.

Results Fatigue (95% CI 0.141 to 0.334, P<.001), expectoration (95% CI 0.107 to 0.305, P<.001) and stuffed nose (95% CI –0.499 to –0.082, P=.006) were identified as the prognostic symptoms of COVID-19 patients from the multivariate analysis. Fever occurred in 603/655 (92.1%) of the patients but was not associated with disease severity. Fatigue accounted for 184/655 (28.1%) of the patients and was linearly associated with infection severity with statistical significance. Expectoration occurred in 169/655 (25.8%) patients in the cohort and was the sole prognostic factor for patients with cardiovascular complications, including hypertension. Shortness of breath, chest distress, muscle or joint ache, and dry cough, which occurred in 33 (5%), 83 (12.7%), 78 (11.9%), and 276 (42.1%) of the 655 patients, respectively, were significantly enriched among patients classified as severe. Stuffed nose and nausea were associated with favorable disease severity, especially among male patients. More female than male patients were documented as having muscle or joint ache. Headache was most enriched in patents aged 15 to 39 years, followed by those aged 40 to 64 years, with statistical significance.

Conclusions Fatigue and expectoration are signs of severe COVID-19 infection. Shortness of breath, chest distress, muscle or joint ache, and dry cough are prevalent in severe patients. Expectoration is commonly present in older individuals and patients with cardiovascular disorders, including hypertension. Shortness of breath is prognostic of severe infection in male patients. Stuffed nose and nausea are favorable prognostic factors of severe infection, especially among male patients.

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9

Jun, 2020

Clinical characteristics of 58 children with a Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2

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Importance  In communities with high rates of coronavirus disease 2019, reports have emerged of children with an unusual syndrome of fever and inflammation.

Objectives  To describe the clinical and laboratory characteristics of hospitalized children who met criteria for the pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PIMS-TS) and compare these characteristics with other pediatric inflammatory disorders.

Design, Setting, and Participants  Case series of 58 children from 8 hospitals in England admitted between March 23 and May 16, 2020, with persistent fever and laboratory evidence of inflammation meeting published definitions for PIMS-TS. The final date of follow-up was May 22, 2020. Clinical and laboratory characteristics were abstracted by medical record review, and were compared with clinical characteristics of patients with Kawasaki disease (KD) (n = 1132), KD shock syndrome (n = 45), and toxic shock syndrome (n = 37) who had been admitted to hospitals in Europe and the US from 2002 to 2019.

Exposures  Signs and symptoms and laboratory and imaging findings of children who met definitional criteria for PIMS-TS from the UK, the US, and World Health Organization.

Main Outcomes and Measures  Clinical, laboratory, and imaging characteristics of children meeting definitional criteria for PIMS-TS, and comparison with the characteristics of other pediatric inflammatory disorders.

Results  Fifty-eight children (median age, 9 years [interquartile range {IQR}, 5.7-14]; 33 girls [57%]) were identified who met the criteria for PIMS-TS. Results from SARS-CoV-2 polymerase chain reaction tests were positive in 15 of 58 patients (26%) and SARS-CoV-2 IgG test results were positive in 40 of 46 (87%). In total, 45 of 58 patients (78%) had evidence of current or prior SARS-CoV-2 infection. All children presented with fever and nonspecific symptoms, including vomiting (26/58 [45%]), abdominal pain (31/58 [53%]), and diarrhea (30/58 [52%]). Rash was present in 30 of 58 (52%), and conjunctival injection in 26 of 58 (45%) cases. Laboratory evaluation was consistent with marked inflammation, for example, C-reactive protein (229 mg/L [IQR, 156-338], assessed in 58 of 58) and ferritin (610 μg/L [IQR, 359-1280], assessed in 53 of 58). Of the 58 children, 29 developed shock (with biochemical evidence of myocardial dysfunction) and required inotropic support and fluid resuscitation (including 23/29 [79%] who received mechanical ventilation); 13 met the American Heart Association definition of KD, and 23 had fever and inflammation without features of shock or KD. Eight patients (14%) developed coronary artery dilatation or aneurysm. Comparison of PIMS-TS with KD and with KD shock syndrome showed differences in clinical and laboratory features, including older age (median age, 9 years [IQR, 5.7-14] vs 2.7 years [IQR, 1.4-4.7] and 3.8 years [IQR, 0.2-18], respectively), and greater elevation of inflammatory markers such as C-reactive protein (median, 229 mg/L [IQR 156-338] vs 67 mg/L [IQR, 40-150 mg/L] and 193 mg/L [IQR, 83-237], respectively).

Conclusions and Relevance  In this case series of hospitalized children who met criteria for PIMS-TS, there was a wide spectrum of presenting signs and symptoms and disease severity, ranging from fever and inflammation to myocardial injury, shock, and development of coronary artery aneurysms. The comparison with patients with KD and KD shock syndrome provides insights into this syndrome, and suggests this disorder differs from other pediatric inflammatory entities.

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