COVID-19 Publications


Dec, 2020

Clinical Charateristrics of 58 Children with a Pediatric Inflmmatory Multisystem Syndrome Temporally Associated with SARS-CoV-2

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Authors: Elizabeth Whittaker, Alasdair Bamford, Julia Kenny, Myrsini Kaforou, Christine E Jones, Priyen Shah, Padmanabhan Ramnarayan, Alain Fraisse, Owen Miller, Patrick Davies, Filip Kucera, Joe Brierley, Marilyn McDougall, Michael Carter, Adriana Tremoulet, Chisato Shimizu, Jethro Herberg, Jane C Burns, Hermione Lyall, Michael Levin, PIMS-TS Study Group and EUCLIDS and PERFORM Consortia

Published in: JAMA Network


Abstract: 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]; 20 girls [34%]) 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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Dec, 2020

Multisystem Inflammatory Syndrome in U.S Children and Adolescents

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Authors: Leora R. Feldstein, Ph.D., Erica B. Rose, Ph.D., Steven M. Horwitz, M.D.

Published in: The New England Journal of Medicine


Abstract: Background: Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19) is important, given the clinical and public health implications of the syndrome.

Methods: We conducted targeted surveillance for MIS-C from March 15 to May 20, 2020, in pediatric health centers across the United States. The case definition included six criteria: serious illness leading to hospitalization, an age of less than 21 years, fever that lasted for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse-transcriptase polymerase chain reaction (RT-PCR), antibody testing, or exposure to persons with Covid-19 in the past month. Clinicians abstracted the data onto standardized forms.

Results: We report on 186 patients with MIS-C in 26 states. The median age was 8.3 years, 115 patients (62%) were male, 135 (73%) had previously been healthy, 131 (70%) were positive for SARS-CoV-2 by RT-PCR or antibody testing, and 164 (88%) were hospitalized after April 16, 2020. Organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%), and respiratory in 131 (70%). The median duration of hospitalization was 7 days (interquartile range, 4 to 10); 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, 90 (48%) received vasoactive support, and 4 (2%) died. Coronary-artery aneurysms (z scores ≥2.5) were documented in 15 patients (8%), and Kawasaki’s disease–like features were documented in 74 (40%). Most patients (171 [92%]) had elevations in at least four biomarkers indicating inflammation. The use of immunomodulating therapies was common: intravenous immune globulin was used in 144 (77%), glucocorticoids in 91 (49%), and interleukin-6 or 1RA inhibitors in 38 (20%).

Conclusions: Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents. (Funded by the Centers for Disease Control and Prevention.)

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Dec, 2020

Multisystem Inflammatory Syndrome in Children in New York State

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Authors: Elizabeth M. Dufort, M.D., Emilia H. Koumans, M.D., M.P.H., Eric J. Chow, M.D., M.P.H., Elizabeth M. Rosenthal, M.P.H., Alison Muse, M.P.H.,  Jemma Rowlands, M.P.H., Meredith A. Barranco, M.P.H.,
Angela M. Maxted, D.V.M., Ph.D.,  Eli S. Rosenberg, Ph.D., Delia Easton, Ph.D.,  Tomoko Udo, Ph.D., et al
Jessica Kumar, D.O.,  for the New York State and Centers for Disease Control and Prevention Multisystem Inflammatory Syndrome in Children Investigation Team

Published in: NEJM


Abstract: Background: A multisystem inflammatory syndrome in children (MIS-C) is associated with coronavirus disease 2019. The New York State Department of Health (NYSDOH) established active, statewide surveillance to describe hospitalized patients with the syndrome.

Methods: Hospitals in New York State reported cases of Kawasaki’s disease, toxic shock syndrome, myocarditis, and potential MIS-C in hospitalized patients younger than 21 years of age and sent medical records to the NYSDOH. We carried out descriptive analyses that summarized the clinical presentation, complications, and outcomes of patients who met the NYSDOH case definition for MIS-C between March 1 and May 10, 2020.

Results: As of May 10, 2020, a total of 191 potential cases were reported to the NYSDOH. Of 95 patients with confirmed MIS-C (laboratory-confirmed acute or recent severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection) and 4 with suspected MIS-C (met clinical and epidemiologic criteria), 53 (54%) were male; 31 of 78 (40%) were black, and 31 of 85 (36%) were Hispanic. A total of 31 patients (31%) were 0 to 5 years of age, 42 (42%) were 6 to 12 years of age, and 26 (26%) were 13 to 20 years of age. All presented with subjective fever or chills; 97% had tachycardia, 80% had gastrointestinal symptoms, 60% had rash, 56% had conjunctival injection, and 27% had mucosal changes. Elevated levels of C-reactive protein, d-dimer, and troponin were found in 100%, 91%, and 71% of the patients, respectively; 62% received vasopressor support, 53% had evidence of myocarditis, 80% were admitted to an intensive care unit, and 2 died. The median length of hospital stay was 6 days.

Conclusions: The emergence of multisystem inflammatory syndrome in children in New York State coincided with widespread SARS-CoV-2 transmission; this hyperinflammatory syndrome with dermatologic, mucocutaneous, and gastrointestinal manifestations was associated with cardiac dysfunction.

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Dec, 2020

Multisystem Inflammatory Syndrome in Children Associated With Coronavirus Disease 2019 in a Children’s Hospital in New York City: Patient Characteristics and an Institutional Protocol for Evaluation, Management, and Follow-Up

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Authors: Brian Jonat, Mark Gorelik, Alexis Boneparth, Andrew S Geneslaw, Philip Zachariah, Amee Shah, Larisa Broglie, Juan Duran, Kimberly D Morel, Maria Zorrilla, Leanne Svoboda 9, Candace Johnson, Jennifer Cheng, Maria C Garzon , Wendy G Silver, Kara Gross Margolis, Cindy Neunert, Irene Lytrivi, Joshua Milner, Steven G Kernie, Eva W Cheung

Published in: Pediatric Critical Care Medicine


Abstract: Objectives: The disease caused by severe acute respiratory syndrome coronavirus 2, known as coronavirus disease 2019, has resulted in a global pandemic. Reports are emerging of a new severe hyperinflammatory syndrome related to coronavirus disease 2019 in children and adolescents. The Centers for Disease Control and Prevention has designated this disease multisystem inflammatory syndrome in children. Our objective was to develop a clinical inpatient protocol for the evaluation, management, and follow-up of patients with this syndrome.

Data Sources: The protocol was developed by a multidisciplinary team based on relevant literature related to coronavirus disease 2019, multisystem inflammatory syndrome in children, and related inflammatory syndromes, as well as our experience caring for children with multisystem inflammatory syndrome in children. Data were obtained on patients with multisystem inflammatory syndrome in children at our institution from the pre-protocol and post-protocol periods.

Data Synthesis: Our protocol was developed in order to identify cases of multisystem inflammatory syndrome in children with high sensitivity, stratify risk to guide treatment, recognize co-infectious or co-inflammatory processes, mitigate coronary artery abnormalities, and manage hyperinflammatory shock. Key elements of evaluation include case identification using broad clinical characteristics and comprehensive laboratory and imaging investigations. Treatment centers around glucocorticoids and IV immunoglobulin with biologic immunomodulators as adjuncts. Multidisciplinary follow-up after discharge is indicated to manage continued outpatient therapy and evaluate for disease sequelae. In nearly 2 months, we admitted 54 patients with multisystem inflammatory syndrome in children, all of whom survived without the need for invasive ventilatory or mechanical circulatory support. After institution of this protocol, patients received earlier treatment and had shorter lengths of hospital stay.

Conclusions: This report provides guidance to clinicians on evaluation, management, and follow-up of patients with a novel hyperinflammatory syndrome related to coronavirus disease 2019 known as multisystem inflammatory syndrome in children. It is based on the relevant literature and our experience. Instituting such a protocol during a global pandemic is feasible and is associated with patients receiving treatment and returning home more quickly.

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Dec, 2020

Addition of Corticosteroids to Immune Globulins is Associated with Recovery of Cardiac function in Multi-inflammatory Syndrome in Children (MIS-C)

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Authors: Zahra Belhadjer, Johanne Auriau, Mathilde Méot, Sylvain Renolleau, Lucile Houyel, Damien Bonnet

Published in: AHA Journals


Introduction: An entity related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection associated with a multisystem inflammatory state in children (MIS-C) and acute heart failure has been described.1 Early treatment of MIS-C has mimicked that of Kawasaki disease with the use of intravenous immunoglobulin (IVIG) and other anti-inflammatory agents.1–3 This strategy seems to be effective because the outcomes are usually favorable with a very limited number of fatalities.1,3 Yet, there is no consensus or evidence for the optimal treatment strategy in MIS-C, and the effect of treatment strategies on the recovery of cardiac function has not been yet described.

We report the evolution of cardiac function in children admitted at our institution for MIS-C, defined by persistent fever (>38.5 °C) for >3 days, multiorgan involvement, evidence for coagulopathy (D-dimers>1000 ng/mL), inflammation (C-reactive protein>80 mg/L), and positive antibody assays for SARS-CoV-2 infection. Three clinical criteria among the following had to be observed to define multiorgan involvement in this series: cervical lymphadenopathy, bulbar conjunctivitis, skin rash, erythema of oral and pharyngeal mucosa, gastrointestinal symptoms, asthenia, respiratory signs, heart failure, or cardiogenic shock.

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Dec, 2020

A national consensus management pathway for paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS): results of a national Delphi process

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Authors: Rachel Harwood, MRCS, Benjamin Allin, Dphil, Christine E Jones, Ph.D., Christine E Jones, PhD, Elizabeth Whittaker, PhD, Padmanabhan Ramnarayan, MD, Athimalaipet V Ramanan, FRCP,

Published in: The Lancet


Summary: Paediatric inflammatory multisystem syndrome temporally associated with COVID-19 (PIMS-TS) is a novel condition that was first reported in April, 2020. We aimed to develop a national consensus management pathway for the UK to provide guidance for clinicians caring for children with PIMS-TS. A three-phase online Delphi process and virtual consensus meeting sought consensus over the investigation, management, and research priorities from multidisciplinary clinicians caring for children with PIMS-TS. We used 140 consensus statements to derive a consensus management pathway that describes the initial investigation of children with suspected PIMS-TS, including blood markers to help determine the severity of disease, an echocardiogram, and a viral and septic screen to exclude other infectious causes of illness. The importance of a multidisciplinary team in decision making for children with PIMS-TS is highlighted throughout the guidance, along with the recommended treatment options, including supportive care, intravenous immunoglobulin, methylprednisolone, and biological therapies. These include IL-1 antagonists (eg, anakinra), IL-6 receptor blockers (eg, tocilizumab), and anti-TNF agents (eg, infliximab) for children with Kawasaki disease-like phenotype and non-specific presentations. Use of a rapid online Delphi process has made it possible to generate a national consensus pathway in a timely and cost-efficient manner in the middle of a global pandemic. The consensus statements represent the views of UK clinicians and are applicable to children in the UK suspected of having PIMS-TS. Future evidence will inform updates to this guidance, which in the interim provides a solid framework to support clinicians caring for children with PIMS-TS. This process has directly informed new PIMS-TS specific treatment groups as part of the adaptive UK RECOVERY trial protocol, which is the first formal randomised controlled trial of therapies for PIMS-TS globally.

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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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Oct, 2020

PAIRED PANDEMICS: Ensuring HIV Care Continuity and Market Stability During COVID-19

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Join this webinar, hosted by CHAI, to get highlights on key trends in the HIV space in LMICs from CHAI’s 2020 HIV Market Report.

You can expect an insightful panel discussion focusing on the resiliency of national HIV programs and markets and ensuring HIV care continuity during these trying times.

Date: November 12 2020

Time: 8am – 9am EST (13 – 14 GMT)

Register to join the webinar here.


Sep, 2020

SARS‐CoV‐2 infection in people living with HIV: a systematic review

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Background and setting Little is known about SARS‐CoV‐2 impact on some vulnerable subgroups, such as people living with HIV/AIDS (PLWHA). In our study we reviewed the current knowledge on SARS‐CoV‐2 cases in PLWHA.

Methods A systematic review was conducted by searching the MEDLINE, EMBASE and Google Scholar databases. Studies reporting data on PLWHA affected by SARS‐CoV‐2 were considered for inclusion. The aim of this study was the systematic characterization of cases of SARS‐CoV‐2 infection among PLWHA, particularly focusing on age, clinical findings at diagnosis, radiological features, therapeutic management and clinical outcomes.

Results Twenty three relevant articles were identified, which reported 164 adults with both HIV and SARS‐CoV‐2 infection. Of those, the large majority were males (120/142, 84.5%), often with one or more comorbidities. Fifteen cases needed intensive care treatment and 16 died. For each group, respectively three patients had underlying comorbidities. There were no studies on children. The included studies were mostly retrospective or case series/reports (19 studies). The overall risk of bias was moderate, due to the study types and characteristics.

Conclusion It is still unclear if HIV infection may influence SARS‐CoV‐2 infection and disease course, however some PLWHA and particularly males affected by ARV‐related complications may be at greater risk of severe Covid‐19 course.


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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