COVID-19: multisystem inflammatory syndrome (MIS-C, MIS-A)
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Epidemiology
- children in convalescent phase of COVID-19
- 80% of children admitted to ICU with underlying condition, most commonly immunodeficiency or cancer[1]
- > 220 known cases of multisystem inflammatory syndrome in adults[6][15]
- higher risk with lower socioeconomic status, hispanic or black ethnicity[11]
Pathology
- inflammation may involve the skin, eyes, blood vessels & heart.
- thought to be a post-infectious immune response[1]
- bears some resemblance to Kawasaki disease
Clinical manifestations
- presents ~4 weeks after onset of acute COVID-19 with extrapulmonary multiorgan dysfunction[15]
- most adults with MIS-A presented with fever (96%), hypotension (60%), cardiac dysfunction (54%), dyspnea (52%), &/or diarrhea (52%)[15]
- 4.5% of adults with MIS-A presented with Kawasaki disease[15]
- higher fever & more symptoms in hospitalized children[7]
- new-onset neurologic symptoms in 50%
- headache & encephalopathy most common[10]
- presentation with myocarditis, hypotension, & inflammation[14]
Laboratory
- lower lymphocyte count in hospitalized children
- higher serum C-reactive protein in hospitalized children[7]
- most adults with MIS-A (90%) have elevated markers of coagulopathy &/or inflammation & positive SARS-CoV2 serology (72%)
Complications
- 57% of adults with MIS-A admitted to ICU, 47% required respiratory support[15]
- mortality in adults with MIS-A is 7%[15]
- children with MIS-C have increased risk of abnormal neurologic findings, working memory impairment, symptoms of depression & somatization, & diminished quality of life 6-12 months after hospital discharge[16]
Differential diagnosis
- compared with patients with COVID-19, patients with MIS-C were more likely
- to be 6-12 years old & non-Hispanic Black[9]
- to have cardiorespiratory involvement, cardiovascular without respiratory involvement, or mucocutaneous without cardiorespiratory involvement vs respiratory involvement
- to have higher neutrophil/lymphocyte ratio (median, 6.4 vs 2.7)
- to have higher serum C-reactive protein level(median, 152 mg/L vs 33 mg/L)
- to have lower platelet count (41% vs 17% < 150,000/uL)[9]
- to be admitted to ICU (74% vs 44%)
Management
- methylprednisolone + intravenous immunoglobulins (IVIG) is associated with better fever outcomes in children[8]
- no evidence that recovery from MIS-C differs with IVIG alone, IVIG + glucocorticoid, or glucocorticoid alone[13]
- delay COVID-19 vaccination for 90 days after diagnosis
- prognosis:
- 4% of children with persistent symptoms at 8 months[14]
References
- ↑ 1.0 1.1 1.2 Orciari Herman A, Sadoughi S, Saitz R COVID-19: Multisystem Inflammatory Syndrome, Physician's First Watch, May 6, 2020 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
Belluck P A New Coronavirus Threat to Children. New York Times. May 6, 2020 https://www.nytimes.com/2020/05/06/health/kawasaki-disease-covid-coronavirus-children.html
Riphagen S, Gomez X, Gonzalez-Martinez C et al Hyperinflammatory shock in children during COVID-19 pandemic. Lancet May 7, 2020 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32386565 Free PMC Article https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31094-1/fulltext
Shekerdemian LS, Mahmood NR, Wolfe KK et al Characteristics and Outcomes of Children With Coronavirus Disease 2019 (COVID-19) Infection Admitted to US and Canadian Pediatric Intensive Care Units. JAMA Pediatr. Published online May 11, 2020. PMID: https://www.ncbi.nlm.nih.gov/pubmed/32392288 https://jamanetwork.com/journals/jamapediatrics/fullarticle/2766037 - ↑ Toubiana J, Poirault C, Corsia A, Kawasaki-like multisystem inflammatory syndrome in children during the covid-19 pandemic in Paris, France: prospective observational study PMID: https://www.ncbi.nlm.nih.gov/pubmed/32493739. BMJ 2020;369:m2094 https://www.bmj.com/content/369/bmj.m2094
- ↑ Whittaker E, Bamford A, Kenny J et al Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2. JAMA. Published online June 8, 2020. PMID: https://www.ncbi.nlm.nih.gov/pubmed/32511692 https://jamanetwork.com/journals/jama/fullarticle/2767209
McCrindle BW, Manlhiot C. SARS-CoV-2-Related Inflammatory Multisystem Syndrome in Children. Different or Shared Etiology and Pathophysiology as Kawasaki Disease? JAMA. Published online June 8, 2020 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32511667 https://jamanetwork.com/journals/jama/fullarticle/2767205 - ↑ Cheung EW, Zachariah P, Gorelik M et al Multisystem Inflammatory Syndrome Related to COVID-19 in Previously Healthy Children and Adolescents in New York City. JAMA. Published online June 8, 2020 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32511676 https://jamanetwork.com/journals/jama/fullarticle/2767207
- ↑ Feldstein LR, Rose EB, Horwitz SM et al Multisystem Inflammatory Syndrome in U.S. Children and Adolescents. N Engl J Med. June 29. 2020 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32598831 https://www.nejm.org/doi/full/10.1056/NEJMoa2021680
Dufort EM, Koumans EH, Chow EJ et al Multisystem Inflammatory Syndrome in Children in New York State. N Engl J Med. June 29. 2020 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32598830 https://www.nejm.org/doi/full/10.1056/NEJMoa2021756
Levin M Childhood Multisystem Inflammatory Syndrome - A New Challenge in the Pandemic. N Engl J Med. June 29. 2020 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32598829 https://www.nejm.org/doi/full/10.1056/NEJMe2023158?query=pfw&jwd=000000793830&jspc=FPG - ↑ 6.0 6.1 Shaigany S, Gnirke M, Guttmann A An adult with Kawasaki-like multisystem inflammatory syndrome associated with COVID-19. The Lancet. July 10, 2020 PMID: https://www.ncbi.nlm.nih.gov/pubmed/32631771 Free PMC article https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31526-9/fulltext
Morris SB, Schwartz NG, Patel P, et al. Case Series of Multisystem Inflammatory Syndrome in Adults Associated with SARS-CoV-2 Infection - United Kingdom and United States, March-August 2020. MMWR Morb Mortal Wkly Rep. ePub: 2 October 2020 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33031361 Free article https://www.cdc.gov/mmwr/volumes/69/wr/mm6940e1.htm - ↑ 7.0 7.1 7.2 Carlin RF et al. Discriminating MIS-C requiring treatment from common febrile conditions in outpatient settings. J Pediatr 2020 Oct 13; [e-pub] PMID: https://www.ncbi.nlm.nih.gov/pubmed/33065115 PMCID: PMC7553071 Free PMC article https://www.jpeds.com/article/S0022-3476(20)31280-4/fulltext
- ↑ 8.0 8.1 Ouldali N, Toubiana J, Antona D et al Association of Intravenous Immunoglobulins Plus Methylprednisolone vs Immunoglobulins Alone With Course of Fever in Multisystem Inflammatory Syndrome in Children. JAMA. Published online February 1, 2021 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33523115 https://jamanetwork.com/journals/jama/fullarticle/2776054
- ↑ 9.0 9.1 9.2 Feldstein LR, Tenforde MW, Friedman KG et al Characteristics and Outcomes of US Children and Adolescents With Multisystem Inflammatory Syndrome in Children (MIS-C) Compared With Severe Acute COVID-19. JAMA. Published online February 24, 2021 PMID: https://www.ncbi.nlm.nih.gov/pubmed/33625505 https://jamanetwork.com/journals/jama/fullarticle/2777026
- ↑ 10.0 10.1 George J New-Onset Neuro Symptoms Common in Kids With MIS-C. Half of pediatric patients in small British study show neurologic involvement. MedPage Today April 13, 2021 https://www.medpagetoday.com/meetingcoverage/aan/92075
Abdel-Mannan O et al Neurologic and radiographic findings associated with Pediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-CoV-2 (PIMS-TS) in Children. American Academy of Neurology (AAN) 2021 - ↑ 11.0 11.1 Javalkar K, Robson VK, Gaffney L et al Socioeconomic and Racial and/or Ethnic Disparities in Multisystem Inflammatory Syndrome. Pediatrics May 2021, 147 (5) e2020039933; PMID: https://www.ncbi.nlm.nih.gov/pubmed/33602802 PMCID: PMC8086000 (available on 2022-05-01) https://pediatrics.aappublications.org/content/147/5/e2020039933
- ↑ Walker M Does a History of MIS-C Preclude COVID Vaccination?
CDC staff addressed considerations for this special population. MedPage Today May 14, 2021 https://www.medpagetoday.com/infectiousdisease/covid19vaccine/92600 - ↑ 13.0 13.1 Son MBF, Murray N, Friedman K et al. Multisystem inflammatory syndrome in children - Initial therapy and outcomes. N Engl J Med 2021 Jul 1; 385:23. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34133855 PMCID: PMC8220972 Free PMC article https://www.nejm.org/doi/10.1056/NEJMoa2102605
McArdle AJ, Vito O, Patel H et al. Treatment of multisystem inflammatory syndrome in children. N Engl J Med 2021 Jul 1; 385:11. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34133854 PMCID: PMC8220965 Free PMC article https://www.nejm.org/doi/10.1056/NEJMoa2102968 - ↑ 14.0 14.1 14.2 Farooqi KM et al. Longitudinal outcomes for multisystem inflammatory syndrome in children. Pediatrics 2021 Aug; 148:e2021051155. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34266903 https://pediatrics.aappublications.org/content/148/2/e2021051155
- ↑ 15.0 15.1 15.2 15.3 15.4 15.5 15.6 15.7 Patel P, DeCuir J, Abrams J et al Clinical Characteristics of Multisystem Inflammatory Syndrome in Adults. A Systematic Review. JAMA Netw Open. 2021;4(9):e2126456. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34550381 https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2784427
- ↑ 16.0 16.1 Rollins CK, Calderon J, Wypij D et al Neurological and Psychological Sequelae Associated With Multisystem Inflammatory Syndrome in Children. JAMA Netw Open. 2023;6(7):e2324369 PMID: https://www.ncbi.nlm.nih.gov/pubmed/37466939 PMCID: PMC10357334 Free PMC article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2807432