Original Investigation
June 8, 2020
JAMA. Published online June 8, 2020. doi:10.1001/jama.2020.10369
Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2
Elizabeth Whittaker, MD1,2; Alasdair Bamford, MD3,4; Julia Kenny, MD5,6; et al
Key Points Question What are the clinical and laboratory characteristics of critically ill children who developed an inflammatory multisystem syndrome during the coronavirus disease 2019 pandemic?
Findings This case series included 58 hospitalized children, a subset of whom required intensive care, and met definitional criteria for pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (PIMS-TS), including fever, inflammation, and organ dysfunction. Of these children, all had fever and nonspecific symptoms, such as abdominal pain (31 [53%]), rash (30 [52%]), and conjunctival injection (26 [45%]); 29 (50%) developed shock and required inotropic support or fluid resuscitation; 13 (22%) met diagnostic criteria for Kawasaki disease; and 8 (14%) had coronary artery dilatation or aneurysms. Some clinical and laboratory characteristics had important differences compared with Kawasaki disease, Kawasaki disease shock syndrome, and toxic shock syndrome.
Meaning These findings help characterize the clinical features of hospitalized, seriously ill children with PIMS-TS and provide insights into this apparently novel syndrome.
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]; 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.
Snip...
Since the first reports of an unusual inflammatory illness in children that emerged in the months following the onset of COVID-19, there have been additional reports from many countries of children with fever and inflammation, for which no cause could be identified, first in health alerts and web exchanges between professional groups, and then in case reports and small case series in rapid publications.2-4 As these cases have emerged in temporal association with the pandemic, a link with SARS-CoV-2 is likely.
COVID-19 AND CHILDREN
Published Online May 6, 2020 https://doi.org/10.1016/ S0140-6736(20)31094-1
Hyperinflammatory shock in children during COVID-19 pandemic
South Thames Retrieval Service in London, UK, provides paediatric intensive care support and retrieval to 2 million children in South East England. During a period of 10 days in mid-April, 2020, we noted an unprecedented cluster of eight children with hyperinflammatory shock, showing features similar to atypical Kawasaki disease, Kawasaki disease shock syndrome,1 or toxic shock syndrome (typical number is one or two children per week). This case cluster formed the basis of a national alert. All children were previously fit and well. Six of the children were of AfroCaribbean descent, and five of the children were boys. All children except one were well above the 75th centile for weight. Four children had known family exposure to coronavirus disease 2019 (COVID-19). Demographics, clinical findings, imaging findings, treatment, and outcome for this cluster of eight children are shown in the table.
Clinical presentations were similar, with unrelenting fever (38–40°C), variable rash, conjunctivitis, peripheral oedema, and generalised extremity pain with significant gastrointestinal symptoms. All progressed to warm, vasoplegic shock, refractory to volume resuscitation and eventually requiring noradrenaline and milrinone for haemodynamic support. Most of the children had no significant respiratory involvement, although seven of the children required mechanical ventilation for cardiovascular stabilisation. Other notable features (besides persistent fever and rash) included development of small pleural, pericardial, and ascitic effusions, suggestive of a diffuse inflammatory process.
All children tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on bronchoalveolar lavage or nasopharyngeal aspirates. Despite being critically unwell, with laboratory evidence of infection or inflammation3 including elevated concentrations of C-reactive protein, procalcitonin, ferritin, triglycerides, and D-dimers, no pathological organism was identified in seven of the children. Adenovirus and enterovirus were isolated in one child.
Baseline electrocardiograms were non-specific; however, a common echocardiographic finding was echobright coronary vessels (appendix), which progressed to giant coronary aneurysm in one patient within a week of discharge from paediatric intensive care (appendix). One child developed arrhythmia with refractory shock, requiring extracorporeal life support, and died from a large cerebrovascular infarct. The myocardial involvement2 in this syndrome is evidenced by very elevated cardiac enzymes during the course of illness.
All children were given intravenous immunoglobulin (2 g/kg) in the first 24 h, and antibiotic cover including ceftriaxone and clindamycin. Subsequently, six children have been given 50 mg/kg aspirin. All of the children were discharged from PICU after 4–6 days. Since discharge, two of the children have tested positive for SARSCoV-2 (including the child who died, in whom SARS-CoV-2 was detected post mortem). All children are receiving ongoing surveillance for coronary abnormalities.
We suggest that this clinical picture represents a new phenomenon affecting previously asymptomatic children with SARS-CoV-2 infection manifesting as a hyperinflammatory syndrome with multiorgan involvement similar to Kawasaki disease shock syndrome. The multifaceted nature of the disease course underlines the need for multispecialty input (intensive care, cardiology, infectious diseases, immunology, and rheumatology).
The intention of this Correspondence is to bring this subset of children to the attention of the wider paediatric community and to optimise early recognition and management. As this Correspondence goes to press, 1 week after the initial submission, the Evelina London Children’s Hospital paediatric intensive care unit has managed more than 20 children with similar clinical presentation, the first ten of whom tested positive for antibody (including the original eight children in the cohort described above).
We declare no competing interests.
*Shelley Riphagen, Xabier Gomez, Carmen Gonzalez-Martinez, Nick Wilkinson, Paraskevi Theocharis shelley.riphagen@gstt.nhs.uk
South Thames Retrieval Service for Children, Evelina London Children’s Hospital Paediatric Intensive Care Unit, London SE1 7EH, UK (SR, XG); and Evelina London Children’s Hospital, London, UK (CG-M, NW, PT)
2 New York Boys Die Of Multi-System Inflammatory Syndrome Affecting Children Amid Coronavirus Pandemic
May 8, 2020 at 11:41 pmFiled Under:Coronavirus, COVID-19, Health, Jessica Layton, Local TV, multi-symptom inflammatory syndrome, New York, Tony Aiello, Valhalla, Westchester County
VALHALLA, N.Y. (CBSNewYork) — A Westchester County boy has died after coming down with an illness affecting dozens of children in New York State.
The 7-year-old boy died late last week at Maria Fareri Children’s Hospital in Valhalla. Dr. Michael Gewitz said he suffered neurological complications from what is now called pediatric multi-system inflammatory syndrome.
Health officials said there have been 73 suspected cases of the illness statewide and investigators are doing a deep dive into the circumstances.
Gov. Andrew Cuomo shared an update Friday, announcing the death of a 5-year-old boy, who CBS2 later confirmed died at Mount Sinai Kravis Children’s Hospital.
“Right now we have a new issue that we’re looking at, which is something we’re just investigating now, but, while rare, we’re seeing some cases where children affected with the COVID virus can become ill with symptoms similar to the Kawasaki disease or Toxic Shock-like syndrome that literally causes inflammation in their blood vessels,” Cuomo said. “This past Thursday, a 5-year-old boy passed away from COVID-related complications, and the State Department of Health is investigating several other cases that presents similar circumstances.”
The hospital said in part, “We must emphasize that based on what we know thus far, it appears to be a very rare condition.”
WATCH: Gov. Cuomo Warns About New Disease Affecting Children Amid Pandemic
It’s still unclear exactly how the syndrome relates to the coronavirus.
The Westchester boy tested positive for COVID-19 antibodies, meaning he was previously infected and had recovered, CBS2’s Tony Aiello reported.
“And we know that in some of the households parents or grandparents or others were diagnosed with COVID and were actually on the record being positive, and apparently the children did not develop symptoms until two to four days before presenting to the hospital for treatment,” said Dr. Dial Hewlett of the Westchester County Department of Health.
“This is very serious. The disease can be fatal, and we want to make sure everyone in Westchester County is aware to be on the lookout for symptoms that may lead to this,” County Executive George Latimer added.
Web Extra: Health Advisory On Pediatric Multi-System Inflammatory Syndrome
Seek care immediately if a child has:
Prolonged fever (more than 5 days)
Difficulty feeding (infants) or is too sick to drink fluids
Severe abdominal pain, diarrhea, or vomiting
Change in skin color – becoming pale, patchy, and/or blue Trouble breathing or is breathing very quickly
Racing heart or chest pain
Decreased amount or frequency of urine Lethargy, irritability, or confusion
“So this is every parent’s nightmare, right? That your child may actually be affected by this virus. But it’s something we have to consider seriously now,” Gov. Cuomo said.
In New Jersey, a 4-year-old child with underlying health issues has also died. It’s unclear if he was affected by the inflammatory syndrome, but there are a handful of other suspected cases in Garden State kids.
“It’s a virus that’s proving to be extremely challenging at every level,” Gov. Phil Murphy said.
Dr. Gewitz said while COVID-19 is likely to infect a large number of children, “most of whom, at least many, are totally asymptomatic. This particular complication is relatively infrequent, unusual.”
SARS-CoV-2 Infection in Children
Of the 1391 children assessed and tested from January 28 through February 26, 2020, a total of 171 (12.3%) were confirmed to have SARS-CoV-2 infection. Demographic data and clinical features are summarized in Table 1. (Details of the laboratory and radiologic findings are provided in the Supplementary Appendix, available with the full text of this letter at NEJM.org.) The median age of the infected children was 6.7 years. Fever was present in 41.5% of the children at any time during the illness. Other common signs and symptoms included cough and pharyngeal erythema. A total of 27 patients (15.8%) did not have any symptoms of infection or radiologic features of pneumonia. A total of 12 patients had radiologic features of pneumonia but did not have any symptoms of infection. During the course of hospitalization, 3 patients required intensive care support and invasive mechanical ventilation; all had coexisting conditions (hydronephrosis, leukemia [for which the patient was receiving maintenance chemotherapy], and intussusception). Lymphopenia (lymphocyte count, <1 .2="" 10-month-old="" 149="" 2020="" 21="" 4="" 6="" 8="" a="" admission.="" after="" and="" as="" been="" bilateral="" child="" common="" condition="" death.="" died="" discharged="" failure="" finding="" from="" general="" ground-glass="" had="" have="" hospital.="" in="" intussusception="" liter="" march="" most="" multiorgan="" of="" one="" opacity="" patients="" per="" present="" radiologic="" span="" stable="" the="" there="" total="" wards="" was="" weeks="" were="" with="">
This report describes a spectrum of illness from SARS-CoV-2 infection in children. In contrast with infected adults, most infected children appear to have a milder clinical course. Asymptomatic infections were not uncommon.2 Determination of the transmission potential of these asymptomatic patients is important for guiding the development of measures to control the ongoing pandemic.
Two COVID-19 infected children, aged 12 and 13, die in Belgium and UK
By Alasdair Sandford with AFP, AP • last updated: 01/04/2020
A health worker in the intensive care ward observes a COVID-19 patient at a hospital in Belgium, March 27, 2020. (AP Photo/Francisco Seco, File)
A 12-year-old girl in Belgium and a 13-year old boy in the UK infected with the novel coronavirus have died, authorities said.
They are believed to be the youngest victims of the disease in their respective countries.
The 12-year-old girl's death was announced during the daily news conference given by Belgium's health service, at the end of its regular update on casualty figures and hospitalisations.
“It's an emotionally difficult moment because it involves a child, and it has also upset the medical and scientific community,” said spokesman Dr Emmanuel André, visibly upset.
"We are thinking of her family and friends. It's a very rare event, but one which devastates us."
Another spokesman added that the child had had a fever for three days and had tested positive for the coronavirus. No other details were given of the girl's background.
Until now the youngest person to die from the virus in Belgium was a 30-year-old female nurse, according to Belgian media.
Just a few hours later, London's King's College Hospital announced that a 13-year-old COVID-19 patient had also died.
"Sadly, a 13-year old boy who tested positive for COVID-19 has passed away, and our thoughts and condolences are with the family at this time," a Trust spokesperson said in a statement.
"The death has been referred to the Coroner," it added.
An appeal posted on the GoFunMe crowdfunding platform by Madinah College, named him as Ismail and said that he didn't have "any pre-existing health conditions.
"Sadly he died without any family members close by due to the highly infectious nature of COVID-19," it added.
Ismail is believed the be the youngest victim of the disease in the UK.
Last week French authorities said a 16-year-old girl had died at a children's hospital in Paris. The death of the teenager, identified as Julie A. and described as otherwise healthy, has provoked strong emotions in France.
Coronavirus in France: healthy 16 year-old dies of COVID-19
Deaths from COVID-19 among people so young are exceptional. Health authorities have said previously that serious cases of the illness -- although predominant in older and more vulnerable age groups -- can occur in adults of any age.
Last weekend the US state of Illinois announced the death of an infant under one year old who had tested positive for coronavirus. The cause of death was being investigated. Medical reports on cases in China have documented the death of a 10-month-old baby and a 14-year-old boy.
A recent US study by the Centers for Disease Control and Prevention (CDC) of 2,500 patients found no cases of deaths among people aged under 19. But it did find that people of all ages were liable to become seriously ill: more than a third of those hospitalised were aged between 20 and 54.
Coronavirus in Europe: Latest numbers on COVID-19 cases and deaths
The Belgian girl's death was included among the latest national figures released on Tuesday, confirming nearly 200 more deaths since the previous update. More than 700 people in the country have died from coronavirus since the outbreak began.
Hospitals in three regions have been particularly badly affected, the authorities say -- around Brussels, in Limburg in eastern Flanders, and in Hainaut in Wallonia to the west.
With 12,775 confirmed COVID-19 cases as of Tuesday, Belgium has the 10th highest number of infections among countries worldwide, according to data compiled by the US Johns Hopkins University Coronavirus Resource Center.
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