COVID-19 Publications

19

Mar, 2021

Characteristics of SARS-CoV-2 patients dying in Italy Report based on available data on March 1st, 2021

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Authors: Luigi Palmieri, Elvira Agazio, Xanthi Andrianou, Pierfrancesco Barbariol, Antonino Bella, Eva Benelli, Luigi Bertinato, Matilde Bocci, Stefano Boros, Giovanni Calcagnini, Marco Canevelli, Federica Censi, Alessandra Ciervo, Elisa Colaizzo, Martina Del Manso, Corrado Di Benedetto, Chiara Donfrancesco, Massimo Fabiani, et al.

Published in: Epicentro

 

Sample: The present report describes the characteristics of 96,149 SARS-CoV-2 patients dying in Italy*, as reported by the Integrated Covid-19 Surveillance System coordinated by the National Institute of Health-ISS. Geographic distribution across the 19 regions and 2 autonomous provinces of Trento and Bozen is presented in Table 1. Absolute number and percentage of deaths are reported according to the 3 phases that characterized the pandemic from the beginning in 2020 to the 1st of March 2021: the first wave (March-May 2020), the low incidence phase (June-September 2020), and the second wave (October 2020 – March 2021), the latter is still ongoing. The surveillance data on deaths are constantly updated and consolidated and both activities require time to be carried out. Each Region has its own organization for updating data and related execution times. Therefore, when reading the data by Region, it is necessary to take into account that the timing of notification, control, verification and updating of data varies from Region to Region and from period to period; this may involve variations (increasing and/or decreasing) and differences both with the data already published in the previous reports, and with the data published by the Civil Protection. It should also be considered that the regional differences in the percentage of deaths reported in the table should not be interpreted in terms of risk. In fact, case fatality depends on the number of infections occurring in each region over a period of time compatible with the possible observation of the fatal event. In this regard, it should also be taken into account that the difference between the number of infections and the notified cases may vary regionally and over time as a function of different test access strategies adopted during the epidemic, thus distorting the comparison of regional case fatality.

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19

Mar, 2021

Virological and immunological features of SARS COV 2 infected children who who developed neutralizing antibodies

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Authors: Nicola Cotugno, Alessandra Ruggiero, Francesco Bonfante, Paolo Rossi, Anita De Rossi, Paolo Palma et al.

Published in: Cell Reports

 

Summary: As the global COVID-19 pandemic progresses, it is paramount to gain knowledge on adaptive immunity to SARS-CoV-2 in children to define immune correlates of protection upon immunization or infection. We analyzed anti-SARS-CoV-2 antibodies and their neutralizing activity (PRNT) in 66 COVID-19-infected children at 7 (±2) days after symptom onset. Individuals with specific humoral responses presented faster virus clearance and lower viral load associated with a reduced in vitro infectivity. We demonstrated that the frequencies of SARS-CoV-2-specific CD4+CD40L+ T cells and Spike-specific B cells were associated with the anti-SARS- CoV-2 antibodies and the magnitude of neutralizing activity. The plasma proteome confirmed the association between cellular and humoral SARS-CoV-2 immunity, and PRNT+ patients show higher viral signal transduction molecules (SLAMF1, CD244, CLEC4G). This work sheds lights on cellular and humoral anti-SARS-CoV-2 responses in children, which may drive future vaccination trial endpoints and quarantine measures policies.

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23

Feb, 2021

What does 95% COVID-19 vaccine efficacy really mean?

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Author: Piero Olliaro

Published in: The Lancet

Introduction: It is imperative to dispel any ambiguity about how vaccine efficacy shown in trials translates into protecting individuals and populations. The mRNA-based Pfizer1,2 and Moderna3 vaccines were shown to have 94–95% efficacy in preventing symptomatic COVID-19, calculated as 100 × (1 minus the attack rate with vaccine divided by the attack rate with placebo). It means that in a population such as the one enrolled in the trials, with a cumulated COVID-19 attack rate over a period of 3 months of about 1% without a vaccine, we would expect roughly 0·05% of vaccinated people would get diseased. It does not mean that 95% of people are protected from disease with the vaccine—a general misconception of vaccine protection also found in a Lancet Infectious Diseases Editorial.

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20

Jan, 2021

Inferring the effectiveness of government interventions against COVID-19

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Published in: The Science Mag

 

Abstract: Governments are attempting to control the COVID-19 pandemic with non-pharmaceutical interventions (NPIs). However, the effectiveness of different NPIs at reducing transmission is poorly understood.

We gathered chronological data on the implementation of NPIs for several European, and other, countries between January and the end of May 2020. We estimate the effectiveness of NPIs, ranging from limiting gathering sizes, business closures, and closure of educational institutions to stay-at-home orders.

To do so, we used a Bayesian hierarchical model that links NPI implementation dates to national case and death counts and supported the results with extensive empirical validation. Closing all educational institutions, limiting gatherings to 10 people or less, and closing face-to-face businesses each reduced transmission considerably. The additional effect of stay-at-home orders was comparatively small.

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20

Jan, 2021

Why schools probably aren’t COVID hotspots

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Data gathered worldwide are increasingly suggesting that schools are not hotspots for coronavirus infections. Despite fears, COVID-19 infections did not surge when schools and day-care centres reopened after pandemic lockdowns eased. And when outbreaks do occur, they mostly result in only a small number of people becoming ill.

However, research also shows that children can catch the virus and shed viral particles, and older children are more likely than very young kids to pass it on to others. Scientists say that the reasons for these trends are unclear, but they have policy implications for older children and teachers.

Globally, COVID-19 infections are still much lower in children than among adults, says Walter Haas, an infectious-diseases epidemiologist at the Robert Koch Institute in Berlin. “They seem rather to follow the situation than to drive it.”

Read the full article by Dyani Lewis here

22

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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22

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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22

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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22

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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22

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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