COVID-19: Multisystem inflammatory syndrome in children (MIS-C) damages the heart to such an extent that some children will need lifelong monitoring and interventions

0
613

Multisystem inflammatory syndrome in children (MIS-C), believed to be linked to COVID-19, damages the heart to such an extent that some children will need lifelong monitoring and interventions, said the senior author of a medical literature review published Sept. 4 in EClinicalMedicine, a journal of The Lancet.

Case studies also show MIS-C can strike seemingly healthy children without warning three or four weeks after asymptomatic infections, said Alvaro Moreira, MD, MSc, of The University of Texas Health Science Center at San Antonio. Dr. Moreira, a neonatologist, is an assistant professor of pediatrics in the university’s Joe R. and Teresa Lozano Long School of Medicine.

“According to the literature, children did not need to exhibit the classic upper respiratory symptoms of COVID-19 to develop MIS-C, which is frightening,” Dr. Moreira said. “Children might have no symptoms, no one knew they had the disease, and a few weeks later, they may develop this exaggerated inflammation in the body.”

Results

The team reviewed 662 MIS-C cases reported worldwide between Jan. 1 and July 25. Among the findings:

  • 71% of the children were admitted to the intensive care unit (ICU).
  • 60% presented with shock.
  • Average length of stay in the hospital was 7.9 days.
  • 100% had fever, 73.7% had abdominal pain or diarrhea, and 68.3% suffered vomiting.
  • 90% had an echocardiogram (EKG) test and 54% of the results were abnormal.
  • 22.2% of the children required mechanical ventilation.
  • 4.4% required extracorporeal membrane oxygenation (ECMO).
  • 11 children died.

“This is a new childhood disease that is believed to be associated with SARS-CoV-2,” Dr. Moreira said.

“It can be lethal because it affects multiple organ systems. Whether it be the heart and the lungs, the gastrointestinal system or the neurologic system, it has so many different faces that initially it was challenging for clinicians to understand.”

The amount of inflammation in MIS-C surpasses two similar pediatric conditions, Kawasaki disease and toxic shock syndrome. “The saving grace is that treating these patients with therapies commonly used for Kawasaki—immunoglobulin and glucocorticosteroids—has been effective,” Dr. Moreira said.

Cardiac abnormalities

Most of the 662 children suffered cardiac involvement as indicated by markers such as troponin, which is used with great accuracy in adults to diagnose heart attacks.

“Almost 90% of the children (581) underwent an echocardiogram because they had such a significant cardiac manifestation of the disease,” Dr. Moreira said.

The damage included:

  • Dilation of coronary blood vessels, a phenomenon also seen in Kawasaki disease.
  • Depressed ejection fraction, indicating a reduced ability for the heart to pump oxygenated blood to the tissues of the body.
  • Almost 10% of children had an aneurysm of a coronary vessel.
  • “This is a localized stretching or ballooning of the blood vessel that can be measured on an ultrasound of the heart,” Dr. Moreira said.

Children with an aneurysm are at the most risk of a future event.

“These are children who are going to require significant observation and follow-up with multiple ultrasounds to see if this is going to resolve or if this is something they will have for the rest of their lives,” Dr. Moreira said.

“And that’s catastrophic to a parent who had a previously healthy child and then he/she is in the very small percentage of individuals who developed MIS-C after COVID-19 infection,” he said.

Another finding from the case studies: Almost half of patients who had MIS-C had an underlying medical condition, and of those, half of the individuals were obese or overweight.

“Generally, in both adults and children, we are seeing that patients who are obese will have a worse outcome,” Dr. Moreira said.

When compared to the initial COVID-19 infection, inflammatory markers in MIS-C were far more abnormal. For instance, troponin, the marker used in adults to diagnose heart attacks, was 50 times its normal level in children with MIS-C.

“Evidence suggests that children with MIS-C have immense inflammation and potential tissue injury to the heart, and we will need to follow these children closely to understand what implications they may have in the long term,” Dr. Moreira said.


In April 2020, during the peak of the coronavirus disease 2019 (COVID-19) pandemic in Europe, a cluster of children with hyperinflammatory shock with features similar to Kawasaki disease and toxic shock syndrome was reported in England* (1).

The patients’ signs and symptoms were temporally associated with COVID-19 but presumed to have developed 2–4 weeks after acute COVID-19; all children had serologic evidence of infection with SARS-CoV-2, the virus that causes COVID-19 (1).

The clinical signs and symptoms present in this first cluster included fever, rash, conjunctivitis, peripheral edema, gastrointestinal symptoms, shock, and elevated markers of inflammation and cardiac damage (1). On May 14, 2020, CDC published an online Health Advisory that summarized the manifestations of reported multisystem inflammatory syndrome in children (MIS-C), outlined a case definition,† and asked clinicians to report suspected U.S. cases to local and state health departments. As of July 29, a total of 570 U.S. MIS-C patients who met the case definition had been reported to CDC.

A total of 203 (35.6%) of the patients had a clinical course consistent with previously published MIS-C reports, characterized predominantly by shock, cardiac dysfunction, abdominal pain, and markedly elevated inflammatory markers, and almost all had positive SARS-CoV-2 test results.

The remaining 367 (64.4%) of MIS-C patients had manifestations that appeared to overlap with acute COVID-19 (2–4), had a less severe clinical course, or had features of Kawasaki disease.§ Median duration of hospitalization was 6 days; 364 patients (63.9%) required care in an intensive care unit (ICU), and 10 patients (1.8%) died. As the COVID-19 pandemic continues to expand in many jurisdictions, clinicians should be aware of the signs and symptoms of MIS-C and report suspected cases to their state or local health departments; analysis of reported cases can enhance understanding of MIS-C and improve characterization of the illness for early detection and treatment.

Local and state health departments reported suspected MIS-C patients to CDC using CDC’s MIS-C case report form, which included information on patient demographics, clinical findings, and laboratory test results. Patients who met the MIS-C case definition and were reported to CDC as of July 29, 2020, were included in the analysis. Latent class analysis (LCA), a statistical modeling technique that can divide cases into groups by underlying similarities, was used to identify and describe differing manifestations in patients who met the MIS-C case definition.

The indicator variables used in the LCA were the presence or absence of SARS-CoV-2–positive test results by reverse transcription–polymerase chain reaction (RT-PCR) or serology, shock, pneumonia, and involvement of organ systems (i.e., cardiovascular, dermatologic, gastrointestinal, hematologic, neurologic, renal, or respiratory).

Three-class LCA was conducted using the R software package “poLCA” with 100 iterations to identify the optimal classification scheme (5). Clinical and demographic variables were reported for patients by LCA class. Chi-squared or Fisher’s exact tests were used to compare proportions of categorical variables; numeric variables, with medians and interquartile ranges, were compared using the Kruskal-Wallis rank sum test.

As of July 29, 2020, a total of 570 MIS-C patients with onset dates from March 2 to July 18, 2020, had been reported from 40 state health departments, the District of Columbia, and New York City (Figure).

The median patient age was 8 years (range = 2 weeks–20 years); 55.4% were male, 40.5% were Hispanic or Latino (Hispanic), 33.1% were non-Hispanic black (black), and 13.2% non-Hispanic white (white) (Table 1). Obesity was the most commonly reported underlying medical condition, occurring in 30.5% of Hispanic, 27.5% of black, and 6.6% of white MIS-C patients.

Overall, the illness in 490 (86.0%) patients involved four or more organ systems. Approximately two thirds did not have preexisting underlying medical conditions before MIS-C onset.

The most common signs and symptoms reported during illness course were abdominal pain (61.9%), vomiting (61.8%), skin rash (55.3%), diarrhea (53.2%), hypotension (49.5%), and conjunctival injection (48.4%). Most patients had gastrointestinal (90.9%), cardiovascular (86.5%), or dermatologic or mucocutaneous (70.9%) involvement.

Substantial numbers of MIS-C patients had severe complications, including cardiac dysfunction (40.6%), shock (35.4%), myocarditis (22.8%), coronary artery dilatation or aneurysm (18.6%), and acute kidney injury (18.4%). The majority of patients (63.9%) were admitted to an ICU. The median length of ICU stay was 5 days (interquartile range = 3–7 days).

Of the 565 (99.1%) patients who underwent SARS-CoV-2 testing, all had a positive test result by RT-PCR or serology; 46.1% had only serologic evidence of infection and 25.8% had only positive RT-PCR test results. Five patients (0.9%) did not have testing performed but had an epidemiologic link as indicated in the MIS-C case definition.

Among all 570 patients, 527 (92.5%) were treated, including 424 (80.5%) who received intravenous immunoglobulin (IVIG), 331 (62.8%) who received steroids, 309 (58.6%) who received antiplatelet medication, 233 (44.2%) who received anticoagulation medication, and 221 (41.9%) who were treated with vasoactive medication. Ten (1.8%) patients were reported to have died (Table 1).

LCA identified three classes of patients, each of which had significantly different illness manifestations related to some of the key indicator variables. Class 1 represented 203 (35.6%) patients who had the highest number of involved organ systems. Within this group, 99 (48.8%) had involvement of six or more organ systems; those most commonly affected were cardiovascular (100.0%) and gastrointestinal (97.5%).

Compared with the other classes, patients in class 1 had significantly higher prevalences of abdominal pain, shock, myocarditis, lymphopenia, markedly elevated C-reactive protein (produced in the liver in response to inflammation), ferritin (an acute-phase reactant), troponin (a protein whose presence in the blood indicates possible cardiac damage), brain natriuretic peptide (BNP), or proBNP (indicative of heart failure) (p<0.01) (Tables 1 and 2).

Almost all class 1 patients (98.0%) had positive SARS-CoV-2 serology test results with or without positive SARS-CoV-2 RT-PCR test results. These cases closely resembled MIS-C without overlap with acute COVID-19 or Kawasaki disease.

Class 2 included 169 (29.6%) patients; among those in this group, 129 (76.3%) had respiratory system involvement. These patients were significantly more likely to have cough, shortness of breath, pneumonia, and acute respiratory distress syndrome (ARDS), indicating that their illnesses might have been primarily acute COVID-19 or a combination of acute COVID-19 and MIS-C. The rate of SARS-CoV-2 RT-PCR positivity (without seropositivity) in this group (84.0%) was significantly higher than that for class 1 (0.5%) or class 3 (2.0%) patients (p<0.01). The case fatality rate among class 2 patients was the highest (5.3%) among all three classes (p<0.01).

Class 3 included 198 (34.7%) patients; the median age of children in this group (6 years) was younger than that of the class 1 patients (9 years) or class 2 patients (10 years) (p<0.01) (Table 1). Class 3 patients also had the highest prevalence of rash (62.6%), and mucocutaneous lesions (44.9%). Although not statistically significant (p = 0.49), the prevalence of coronary artery aneurysm and dilatations (18.2%) was higher than that in class 2 patients (15.8%), but lower than that in class 1 patients (21.1%).

Class 3 patients more commonly met criteria for complete Kawasaki disease (6.6%) compared with class 1 (4.9%) and class 2 (3.0%) patients (p = 0.30), and had the lowest prevalence of underlying medical conditions, organ system involvement, complications (e.g., shock, myocarditis), and markers of inflammation and cardiac damage. Among class 3 patients, 63.1% had positive SARS-CoV-2 serology only and 33.8% had both serologic confirmation and positive RT-PCR results.

CharacteristicNo. (%)p value
Total (N = 570)Latent class analysis group*
Class 1 (n = 203)Class 2 (n = 169)Class 3 (n = 198)
Sex
Female254 (44.6%)87 (42.9%)81 (47.9%)86 (43.4%)0.57
Male316 (55.4%)116 (57.1%)88 (52.1%)112 (56.6%)
Age (yrs), median (IQR)8 (4–12)9 (6–13)10 (5–15)6 (3–10)<0.01
Race/Ethnicity
Hispanic187 (40.5%)62 (36.9%)62 (46.6%)63 (39.1%)0.03
Black, non–Hispanic153 (33.1%)66 (39.3%)39 (29.3%)48 (29.8%)
White, non–Hispanic61 (13.2%)22 (13.1%)15 (11.3%)24 (14.9%)
Other26 (5.6%)8 (4.8%)6 (4.5%)12 (7.5%)
Multiple18 (3.9%)9 (5.4%)5 (3.8%)4 (2.5%)
Asian13 (2.8%)1 (0.6%)3 (2.3%)9 (5.6%)
American Indian/Alaskan Native3 (0.6%)0 (0.0%)3 (2.3%)0 (0.0%)
Native Hawaiian/Pacific Islander1 (0.2%)0 (0.0%)0 (0.0%)1 (0.6%)
Unknown108 (─)35 (─)36 (─)37 (─)
Outcome
Died10 (1.8%)1 (0.5%)9 (5.3%)0 (0.0%)<0.01
Days in hospital, median (IQR)6 (4–9)8 (6–11)6 (4–10)5 (4–8)<0.01
116 (3.2%)3 (1.8%)3 (2.0%)10 (5.4%)<0.01
2–7304 (60.2%)86 (50.3%)87 (58.8%)131 (70.4%)
8–14149 (29.5%)66 (38.6%)41 (27.7%)42 (22.6%)
≥1536 (7.1%)16 (9.4%)17 (11.5%)3 (1.6%)
Missing65 (─)32 (─)21 (─)12 (─)
ICU admission364 (63.9%)171 (84.2%)105 (62.1%)88 (44.4%)<0.01
Days in ICU, median (IQR)5 (3–7)5 (4–7)6 (3–9)3 (2–5)<0.01
Underlying medical conditions<0.01
Obesity146 (25.6%)60 (29.6%)49 (29.0%)37 (18.7%)0.02
Chronic lung disease48 (8.4%)18 (8.9%)17 (10.1%)13 (6.6%)0.46
Clinical characteristic
No. of organ systems involved
2–380 (14.0%)6 (3.0%)24 (14.2%)50 (25.3%)<0.01
4–5351 (61.6%)98 (48.3%)113 (66.9%)140 (70.7%)
≥6139 (24.4%)99 (48.8%)31 (18.3%)9 (4.5%)
Days with fever, median (IQR)5 (3–6)5 (3–6)5 (3–6)5 (3–6)0.81
Kawasaki disease28 (4.9)10 (4.9)5 (3.0)13 (6.6)0.30
Organ system involvement
Gastrointestinal518 (90.9%)198 (97.5%)146 (86.4%)174 (87.9%)<0.01
Abdominal pain353 (61.9%)163 (80.3%)83 (49.1%)107 (54.0%)<0.01
Vomiting352 (61.8%)145 (71.4%)95 (56.2%)112 (56.6%)<0.01
Diarrhea303 (53.2%)124 (61.1%)79 (46.7%)100 (50.5%)0.01
Cardiovascular493 (86.5%)203 (100.0%)143 (84.6%)147 (74.2%)<0.01
Shock202 (35.4%)154 (75.9%)48 (28.4%)0 (0.0%)<0.01
Elevated troponin176 (30.9%)93 (45.8%)43 (25.4%)40 (20.2%)<0.01
Elevated BNP or NT–proBNP246 (43.2%)105 (51.7%)77 (45.6%)64 (32.3%)<0.01
Congestive heart failure40 (7.0%)21 (10.3%)14 (8.3%)5 (2.5%)0.02
Cardiac dysfunction§207 (40.6%)105 (55.3%)64 (46.0%)38 (21.0%)<0.01
Myocarditis130 (22.8%)62 (30.5%)36 (21.3%)32 (16.2%)0.01
Coronary artery dilatation or aneurysm§95 (18.6%)40 (21.1%)22 (15.8%)33 (18.2%)0.49
Hypotension282 (49.5%)162 (79.8%)75 (44.4%)45 (22.7%)<0.01
Pericardial effusion§122 (23.9%)55 (28.9%)32 (23.0%)35 (19.3%)0.01
Mitral regurgitation§130 (25.5%)68 (35.8%)30 (21.6%)32 (17.7%)<0.01
Dermatologic and mucocutaneous404 (70.9%)156 (76.8%)87 (51.5%)161 (81.3%)<0.01
Rash315 (55.3%)121 (59.6%)70 (41.4%)124 (62.6%)<0.01
Mucocutaneous lesions201 (35.3%)70 (34.5%)42 (24.9%)89 (44.9%)<0.01
Conjunctival injection276 (48.4%)118 (58.1%)54 (32.0%)104 (52.5%)<0.01
Hematologic421 (73.9%)161 (79.3%)130 (76.9%)130 (65.7%)<0.01
Elevated D–dimer344 (60.4%)136 (67.0%)104 (61.5%)104 (52.5%)0.01
Thrombocytopenia176 (30.9%)84 (41.4%)45 (26.6%)47 (23.7%)<0.01
Lymphopenia202 (35.4%)82 (40.4%)60 (35.5%)60 (30.3%)0.11
Respiratory**359 (63.0%)155 (76.4%)129 (76.3%)75 (37.9%)<0.01
Cough163 (28.6%)51 (25.1%)67 (39.6%)45 (22.7%)<0.01
Shortness of breath149 (26.1%)66 (32.5%)59 (34.9%)24 (12.1%)<0.01
Chest pain or tightness66 (11.6%)33 (16.3%)24 (14.2%)9 (4.5%)0.01
Pneumonia††110 (19.3%)47 (23.2%)62 (36.7%)1 (0.5%)<0.01
ARDS34 (6.0%)14 (6.9%)17 (10.1%)3 (1.5%)<0.01
Pleural effusion§§86 (15.8%)49 (24.7%)29 (18.4%)8 (4.2%)<0.01
Neurologic218 (38.2%)107 (52.7%)70 (41.4%)41 (20.7%)<0.01
Headache186 (32.6%)90 (44.3%)63 (37.3%)33 (16.7%)<0.01
Renal105 (18.4%)77 (37.9%)28 (16.6%)0 (0.0%)<0.01
Acute kidney injury105 (18.4%)77 (37.9%)28 (16.6%)0 (0.0%)<0.01
Other
Periorbital edema27 (4.7%)13 (6.4%)5 (3.0%)9 (4.5%)0.32
Cervical lymphadenopathy >1.5 cm diameter76 (13.3%)28 (13.8%)18 (10.7%)30 (15.2%)0.43
SARS COV–2 testing
Any laboratory test done565 (99.1%)200 (98.5%)169 (100.0%)196 (99.0%)0.39
Any positive laboratory test¶¶ (% among tested)565 (100.0%)200 (100.0%)169 (100.0%)196 (100.0%)NA
PCR positive/Serology negative, not done, or missing***147 (25.8%)1 (0.5%)142 (84.0%)4 (2.0%)<0.01
Serology positive/PCR negative†††263 (46.1%)138 (68.0%)0 (0.0%)125 (63.1%)<0.01
PCR positive/Serology positive155 (27.2%)61 (30.0%)27 (16.0%)67 (33.8%)<0.01
Epidemiologic link only, with no testing5 (0.9%)3 (1.5%)0 (0.0%)2 (1.0%)<0.01
Treatment§§§
IVIG¶¶¶424 (80.5%)174 (87.9%)96 (62.7%)154 (87.5%)<0.01
Steroids331 (62.8%)145 (73.2%)80 (52.3%)106 (60.2%)<0.01
Antiplatelet medication309 (58.6%)113 (57.1%)69 (45.1%)127 (72.2%)<0.01
Anticoagulation medication233 (44.2%)92 (46.5%)76 (49.7%)65 (36.9%)0.03
Vasoactive medications221 (41.9%)129 (65.2%)64 (41.8%)28 (15.9%)<0.01
Respiratory support, any201 (38.1%)104 (52.5%)79 (51.6%)18 (10.2%)<0.01
Intubation and mechanical ventilation69 (13.1%)37 (18.7%)30 (19.6%)2 (1.1%)<0.01
Immune modulators119 (22.6%)52 (26.3%)34 (22.2%)33 (18.8%)0.18
Dialysis2 (0.4%)0 (0.0%)2 (1.3%)0 (0.0%)0.08
Abbreviations: ARDS = acute respiratory distress syndrome; BNP = brain natriuretic peptide; ICU = intensive care unit; IQR = interquartile range; IVIG = intravenous immune globulin; NT-proBNP = N-terminal pro b-type natriuretic peptide; PCR = polymerase chain reaction.
* Latent class analysis (LCA) is a statistical modeling technique in which observations can be classified into latent classes based on their underlying similarities. Variables that are associated with MIS-C clinical manifestation were selected as indicator variables and included in the LCA model.
 Patient had fever, rash, conjunctival injection, cervical lymphadenopathy >1.5 cm diameter, and mucocutaneous lesions.
§ Percentages calculated among 510 persons with an echocardiogram performed.
 Thrombocytopenia was defined as a platelet count of less than 150 x 103 per μl or if thrombocytopenia was checked on the case-report form. Lymphopenia was defined as a lymphocyte count of <4,500 cells per μl for infants aged <8 months, or less than 1,500 cells per ml for persons aged ≥8 months.
**Among 359 with respiratory organ system involvement, 324 (90%) also had cardiovascular system involvement.
†† Information about pneumonia was collected on the case report form under signs and symptoms, complications, or chest imaging.
§§ Percentages calculated among 545 persons with either an echocardiogram or chest imaging performed.
¶¶ Eight cases had a positive SARS CoV–2 antigen test result, among whom three were also positive by both PCR and serology, one was positive by PCR alone, and one was positive by serology alone.
*** Among 147 cases with a positive PCR result without a positive serologic test result, 10 had a negative serologic test, and the remaining had unknown serologic testing.
††† Among 263 cases with positive serologic test result without a positive PCR result, 254 had a negative PCR result, and the remaining had unknown PCR testing.
§§§ Percentages calculated among 527 persons who received treatment.
¶¶¶ 73 received a second dose of IVIG.
LCA class 1LCA class 2LCA class 3p-value
 Laboratory testNo.MedianIQRNo.MedianIQRNo.MedianIQR
Fibrinogen, peak (mg/dL)151557(449–713)87566(430–662)105546(426–681)0.67
D-dimer, peak (mg/L)1583.0(1.6–4.9)1062.6(1.2–5.1)1281.7(0.8–3.2)<0.01
Troponin, peak (ng/mL)1620.09(0.02–0.48)1090.05(0.01–0.30)1300.01(0.01–0.08)<0.01
BNP, peak (pg/mL)531,321(414–2,528)30198(76–927)25182(30–616)<0.01
proBNP, peak (ng/L)1034,700(1,261–13,646)681,503(247–6,846)92507(176–2,153)<0.01
start highlightCRP, peak (mg/L)end highlight16621(14–29)12216(9–25)14414(6–23)<0.01
Ferritin, peak (ng/mL)159610(347–1,139)108422(207–825)132242(116–466)<0.01
IL-6, peak (pg/mL)5465(24–258)2741(21–131)2969(7–118)0.24
Platelets, nadir (103 cells/μl)115131(102–203)76172(103–245)68150(113–237)0.15
Lymphocytes, nadir (cells/μl)72695(400–1,093)491,200(790–2,025)421,420(723–2,250)<0.01
Abbreviations: BNP = brain natriuretic peptide; CRP = C-reactive protein; IL-6 = Interleukin-6; IQR = interquartile range.
* Latent class analysis (LCA) is a statistical modeling technique in which observations can be classified into latent classes based on their underlying similarities. Variables that are associated with MIS-C clinical manifestation were selected as indicator variables and included in the LCA model.

References

  1. Riphagen S, Gomez X, Gonzalez-Martinez C, Wilkinson N, Theocharis P. Hyperinflammatory shock in children during COVID-19 pandemic. Lancet 2020;395:1607–8. CrossRefexternal icon PubMedexternal icon
  2. Toubiana J, Poirault C, Corsia A, et al. Outbreak of Kawasaki disease in children during COVID-19 pandemic in Paris, France: prospective observational study. BMJ 2020;369:m2094. CrossRefexternal icon PubMedexternal icon
  3. Belhadjer Z, Méot M, Bajolle F, et al. Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic. Circulation 2020. E-pub May 17, 2020.
  4. Verdoni L, Mazza A, Gervasoni A, et al. An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. Lancet 2020;395:1771–8. CrossRefexternal icon PubMedexternal icon
  5. Linzer DA, Lewis JB. poLCA: An R package for polytomous variable latent class analysis. J Stat Softw 2011;42:1–29. CrossRefexternal icon
  6. Dufort EM, Koumans EH, Chow EJ, et al.; New York State and CDC Multisystem Inflammatory Syndrome in Children Investigation Team. Multisystem inflammatory syndrome in children in New York State. N Engl J Med 2020;383:347–58. CrossRefexternal icon PubMedexternal icon
  7. Whittaker E, Bamford A, Kenny J, et al.; PIMS-TS Study Group and EUCLIDS and PERFORM Consortia. Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2. JAMA 2020;324:259–69. CrossRefexternal icon PubMedexternal icon
  8. Feldstein LR, Rose EB, Horwitz SM, et al.; Overcoming COVID-19 investigators and the CDC COVID-19 Response Team. Multisystem inflammatory syndrome in U.S. children and adolescents. N Engl J Med 2020;383:334–46. CrossRefexternal icon PubMedexternal icon
  9. Bialek S, Gierke R, Hughes M, McNamara LA, Pilishvili T, Skoff T; CDC COVID-19 Response Team. Coronavirus disease 2019 in children—United States, February 12–April 2, 2020. MMWR Morb Mortal Wkly Rep 2020;69:422–6. CrossRefexternal icon PubMedexternal icon
  10. Stokes EK, Zambrano LD, Anderson KN, et al. Coronavirus disease 2019 case surveillance—United States, January 22–May 30, 2020. MMWR Morb Mortal Wkly Rep 2020;69:759–65. CrossRefexternal icon PubMedexternal icon

More information: Mubbasheer Ahmed et al, Multisystem inflammatory syndrome in children: A systematic review, EClinicalMedicine (2020). DOI: 10.1016/j.eclinm.2020.100527

LEAVE A REPLY

Please enter your comment!
Please enter your name here

Questo sito usa Akismet per ridurre lo spam. Scopri come i tuoi dati vengono elaborati.