Multisystem inflammatory syndrome identified in adults


Published by: The Public Health Agency of Canada
Issue: Volume 47-7/8: Infant Botulism in Canada, 1979–2019
Date published: July/August 2021
ISSN: 1481-8531
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Volume 47-7/8: Infant Botulism in Canada, 1979–2019
Rapid Communication
Epidemiologic and clinical characteristics of multisystem inflammatory syndrome in adults: a rapid review
Nicole Atchessi1, Rojiemiahd Edjoc1, Megan Striha1, Lisa Waddell2, Natalie Bresee3, Thomas Dawson1
Affiliations
1 Health Security Infrastructure Branch, Public Health Agency of Canada, Ottawa, ON
2 Public Health Risk Sciences Division, National Microbiology Laboratory, Public Health Agency of Canada, Guelph, ON
3 Children’s Hospital of Eastern Ontario, Ottawa, ON
Correspondence
Suggested citation
Atchessi N, Edjoc R, Striha M, Waddell L, Bresee N, Dawson T. Epidemiologic and clinical characteristics of multisystem inflammatory syndrome in adults: a rapid review. Can Commun Dis Rep 2021;47(7/8):305–15. https://doi.org/10.14745/ccdr.v47i78a03
Keywords: COVID-19, SARS-CoV-2, MIS-A, MIS-C, multisystem inflammatory syndrome in adult
Abstract
Multisystem inflammatory disease in children (MIS-C) is one of the severe presentations of the coronavirus disease 2019 (COVID-19) that has been described in the literature since the beginning of the pandemic. Although MIS-C refers to children, cases with similar clinical characteristics have been recently described in adults. A description of the epidemiologic and clinical characteristics of multisystem inflammatory disease in adults (MIS-A) is a starting point for better knowledge and understanding of this emerging disease.
We identified nine case reports of MIS-A in the literature, five from the United States, two from France and two from the United Kingdom. The case descriptions revealed similarities in clinical features, including occurrence during post-acute disease phase, fever, digestive symptoms, cardiac involvement and elevated inflammatory markers. All the patients were hospitalized, three required admission to the intensive care unit and one died. The most common treatments were intravenous immunoglobulin, prednisolone and aspirin.
These findings suggest that MIS-A is a severe complication of COVID-19 disease that can lead to death. Further studies to improve our understanding of the pathogenesis of MIS-A, which will help improve treatment decisions and prevent sequelae or death.
Introduction
The coronavirus disease 2019 (COVID-19) is a novel disease resulting from infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Footnote 1. As of May 29, 2021, the virus has infected more than 170 million people and caused more than 3.5 million deaths worldwideFootnote 2.
The clinical characteristics of COVID-19 disease vary from asymptomatic to severe. The most common symptoms are fever, cough, diarrhea and dyspneaFootnote 3. There are three clinical stagesFootnote 4. The first stage is characterized by infection with SARS-CoV-2, with flu-like symptoms in certain cases. The second stage, characterized by viral pneumonia, possibly combined with pulmonary inflammation and coagulopathy, can require hospitalization and even mechanical ventilation. The third stage of the disease is characterized by fibrosis.
Multisystem inflammatory syndrome has been widely reported in childrenFootnote 5 and, more recently, in adultsFootnote 6. In children, multisystem inflammatory syndrome (MIS-C) is a severe presentation that has been described in the literature since the beginning of the pandemic. Although MIS-C is defined as restricted to children, similar clinical characteristics have been described in adults. Knowing the epidemiologic and clinical characteristics of multisystem inflammatory syndrome cases in adults (MIS-A) provides a starting point to a better understanding of this emerging disease.
Methods
A database at the Public Health Agency of Canada is populated daily with new COVID-19 literature using standardized algorithms [e.g. "COVID-19" OR "SARS-CoV-2" OR "SARS-Coronoavirus-2" OR "nCov" OR "novel CoV" OR ("novel AND coronavirus")] tailored to each searched database, that is, PubMed, Scopus, BioRxiv, MedRxiv, ArXiv, SSRN and Research Square. The literature is cross-referenced with the COVID-19 information centres run by the Lancet, the BMJ, Elsevier and Wiley.
Our search through the Public Health Agency of Canada database included studies published in English since the start of the pandemic until November 13, 2020. We gathered details about COVID-19-related studies in a RefWorks database and an Excel spreadsheet that are searchable by topic. Search terms used to retrieve the MIS-A literature from titles and abstracts in the Excel spreadsheet included "MIS-A," "Kawasaki," "multisystem inflam*," "multi-system inflam*," "inflammatory multisystem," "inflammatory multi-system," "inflammatory disease," "Kawasaki-like" and "COVID-19 linked disease." We screened articles (n=314) for relevance and included those that described MIS-A with a COVID-19 link (see Appendix A and Appendix B). We excluded paediatric cases and studies with cases similar to a MIS-A, but not formally diagnosed as MIS-A as per the authors. Since MIS-A is an emerging disease, a case definition does not yet exist. Authors of studies included in this review based case selection on the definition of MIS-C, while excluding the age criteria (see Appendix C).
Results
We identified nine case reports of MIS-A in the literature, five in the United States, two in France and two in the United Kingdom.
All nine cases of MIS-A occurred in relatively young adults, with a median age of 31 years (interquartile range [IQR]=25-45 years). Six patients were maleFootnote 6Footnote 7Footnote 8Footnote 9Footnote 10Footnote 11. Six studies reported ethnicity: three patients were of African origin or African AmericanFootnote 6Footnote 8Footnote 12, two were of Hispanic originFootnote 11Footnote 13 and one was WhiteFootnote 10. Seven out of nine studies reported on comorbidity. Two patients had both hypertension and obesityFootnote 6Footnote 12; one of these patients also had diabetesFootnote 12. Four patients had no known comorbiditiesFootnote 7Footnote 8Footnote 10Footnote 13; in three cases the comorbidity status was not reportedFootnote 7Footnote 9Footnote 14.
All nine patients underwent a reverse transcription polymerase chain reaction (RT-PCR) test for COVID-19. Five had negative RT-PCR results but positive serology testsFootnote 6Footnote 7Footnote 8Footnote 10Footnote 13. One had a negative RT-PCR result despite having had a positive RT-PCR result a few days earlierFootnote 12. The results of RT-PCR swab test and serology were both positive in one caseFootnote 14. The two remaining patients had a positive RT-PCR test but did not have serology testsFootnote 9Footnote 11. These findings suggested that MIS-A probably occurred during the post-acute phase of the disease.
All the patients presented with fever. Seven had a fever for 5 to 7 days prior to hospital admission, while two did not report fever duration. Most (n=7) had digestive symptoms upon admissionFootnote 7Footnote 9Footnote 10Footnote 11Footnote 12Footnote 13Footnote 14, with the most common diarrhea (n=6), followed by vomiting (n=4) and bilateral enlarged parotid glands (n=1). Rash (n=4) (8-10,14) and neck pain (n=3)Footnote 11Footnote 12Footnote 13 with or without lymphadenopathy were also common.
There was multi-organ effect in all cases. Involvement of the cardiovascular system was the most common (n=7)Footnote 6Footnote 7Footnote 10Footnote 12Footnote 13Footnote 14Footnote 15 and was documented via echocardiography in four cases. The four cases had an acute myocardial dysfunction with left ventricular systolic dysfunction and pericardial effusion. Two had ventricular fibrillationFootnote 11Footnote 12 and two other a dilated inferior vena cava Footnote 10Footnote 14. One of these patients also had overloaded right ventricular pressure and mild enlargement of the main pulmonary artery and hyperkinetic left ventricleFootnote 14.
The other manifestations were digestive (n=7)Footnote 7Footnote 9Footnote 10Footnote 11Footnote 12Footnote 13Footnote 14, ophthalmic (n=6)Footnote 8Footnote 9Footnote 10Footnote 11Footnote 13Footnote 14, renal (n=4)Footnote 6Footnote 11Footnote 12Footnote 14, dermatologic (n=5)Footnote 6Footnote 8Footnote 9Footnote 10Footnote 13, pulmonary (n=2)Footnote 7Footnote 12 and neurologic (n=1)Footnote 6.
C-reactive protein (CRP) test results and lymphocyte counts were reported in eight cases, and D-dimers and troponin in six cases. All cases had elevated inflammatory markers. The inflammatory markers that were most commonly elevated were CRP (n=8)Footnote 6Footnote 7Footnote 9Footnote 10Footnote 11Footnote 12Footnote 13Footnote 14, followed by D-dimers (n=6)Footnote 7Footnote 9Footnote 11Footnote 12Footnote 13Footnote 14 and troponin (n=6)Footnote 6Footnote 7Footnote 8Footnote 9Footnote 10Footnote 11. Lymphopenia was also common (n=6)Footnote 7Footnote 8Footnote 9Footnote 11Footnote 12Footnote 14. Three authors excluded rheumatic disease, HIV and hepatitis infectionFootnote 9Footnote 11Footnote 13.
Intravenous immunoglobulin (IVIG; n=4)Footnote 8Footnote 9Footnote 11Footnote 14, prednisolone (n=3)Footnote 9Footnote 11Footnote 13 and aspirin (n=3)Footnote 7Footnote 13Footnote 14 were the most common treatments. Immunoglobulin was not given in one case because the patient responded well to aspirinFootnote 7. In another case, prednisolone was not provided because the patient had a concomitant tracheal aspiration positive for Klebsiella aerogenes (syn: Enterobacter aerogenes) that was then treated with trimethoprim sulfamethoxazoleFootnote 6. One patient did not receive any specific treatment; she died while being evaluated for admissionFootnote 12.
Of the nine patients, one diedFootnote 12 and the outcome of another was not reportedFootnote 9. Three patients had severe symptoms, requiring admission to the intensive care unit (ICU), but recovered Footnote 6Footnote 7Footnote 14. Two patients presented with hypotension and tachycardia upon admission but did not require admission to ICU and recoveredFootnote 11Footnote 13. One patient presented with vasoplegic shock upon admission, had a length of stay in hospital of eight days and recovered under treatmentFootnote 8. One case did not demonstrate shock-like signs and recovered under treatmentFootnote 9. The case that died had been previously hospitalized for COVID-19 and discharged 12 days earlier; upon readmission she presented with rapid onset of fever and developed hemodynamic instability and ventricular fibrillation and could not be resuscitated.
Discussion
MIS-A appears to be a rare complication of COVID-19 disease. The RT-PCR and serology results and the absence of pulmonary involvement in most cases are consistent with MIS-A occurring during the post-acute phase of COVID-19 disease.
The clinical characteristics of MIS-A share similarities with MIS-C. The pathogenesis of MIS-C involves immune dysregulation similar to Kawasaki disease, macrophage activation syndrome (MAS) and cytokine release syndromeFootnote 16Footnote 17. Kawasaki disease is theorized to be from an aberrant immune response to a possible infectious trigger; it is described in children and less often in adultsFootnote 15Footnote 18. In the case of MIS-A, the pathogenesis is not fully understoodFootnote 19. Endothelial damage seems to have led to serious complications with multi-organ involvement in the reported casesFootnote 12. This process probably occurs post-infection based on the timing of the rise of MIS-C cases and peak of COVID-19 in the communities in which these cases were foundFootnote 16Footnote 17.
While we identified some common features, the clinical presentations in the case reports of the MIS-A patients varied. For example, ophthalmologic signsFootnote 9 were predominant in one case and cardiac signs in anotherFootnote 6. Further studies are required on MIS-C pathophysiology and how it contributes to MIS-A pathogenesis.
The approach to management of children with MIS-C is evolving; management does require multidisciplinary care and a case-by-case approach. Since MIS-C is most likely a post-infectious complication rather than an active infection, the role of antivirals is not clearFootnote 20. Those that meet the criteria for Kawasaki disease may benefit from IVIG, as might those with moderate to severe MIS-CFootnote 20. Patients who may benefit from this treatment may include those with cardiac involvement or in shock states. Steroids might be considered for those who have severe or refractory shockFootnote 20. Other adjunctive therapies (IL-1 inhibitors or convalescent plasma) and their place in the treatment of MIS-C is uncertainFootnote 20. How these treatment options can be applied to MIS-A patients is also currently unknown. We need further studies outside of controlled clinical trials to ascertain the role of IVIG, steroids and other immunomodulatory agents in treating suspected cases of MIS-AFootnote 21.
Limitations
We based this current review on nine case reports from three countries. Although case reports can help in identifying new trends or diseases, there are limitations. Information from the case reports is difficult to generalize because patients have different backgrounds and are not representative of the population.
Currently, there is no case definition for MIS-A. Using the MIS-C case definition (minus age) has its challenges, as there are at least four definitions (see Appendix C). In addition, how each case met the definition was not always clear. For example, authors of the case reports did not always specify how they excluded all other potential causes of the multisystem inflammatory syndrome or report the duration of fever or presence of comorbidities. There was also a lack of information about ethnicity and severity of the disease. For example, when hypotension was identified, the presence or absence of shock-like syndrome was not always specified.
These are preliminary findings; additional studies will lead to a better understanding of common epidemiologic and clinical characteristics of this condition.
Conclusion
The case descriptions revealed similarities in clinical features such as fever, digestive symptoms, cardiac involvement and elevated inflammatory markers. The RT-PCR and serology results and the absence of pulmonary involvement suggest that MIS-A occurred during the post-acute phase of COVID-19 disease. All patients were hospitalized, three required admission to the ICU and one died. The most common treatments were IVIG, prednisolone and aspirin.
The findings suggest that MIS-A is a severe complication of COVID-19 disease that can lead to death. Early recognition of MIS-A may improve outcomes. A case definition for MIS-A is needed to help standardize reporting and facilitate disease recognition. Further studies to improve our understanding of pathogenesis of MIS-A will help improve treatment decisions and prevent sequelae and death.
Authors' statement
- NA — Methodology, investigation, writing—original draft
- RE — Conceptualization, writing—review and editing, supervision
- MS — Writing-review and editing
- LW — Writing-review and editing
- NB — Writing-review and editing
- TD — Writing-review and editing
Competing interests
None.
Acknowledgments
We acknowledge our collaborators at the Emerging Science Group for their help in this work.
Funding
None.
References
- Footnote 1
-
Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. JAMA 2020;323(13):1239-42. https://doi.org/10.1001/jama.2020.2648
- Footnote 2
-
Worldometer. Worldometer COVID-19 coronavirus pandemic [Internet]. (updated 2020-05-29; accessed 2020-05-29). https://www.worldometers.info/coronavirus/
- Footnote 3
-
Manabe T, Akatsu H, Kotani K, Kudo K. Trends in clinical features of novel coronavirus disease (COVID-19): A systematic review and meta-analysis of studies published from December 2019 to February 2020. Respir Investig 2020;58(5):409-18. https://doi.org/10.1016/j.resinv.2020.05.005
- Footnote 4
-
Polak SB, Van Gool IC, Cohen D, von der Thüsen JH, van Paassen J. A systematic review of pathological findings in COVID-19: a pathophysiological timeline and possible mechanisms of disease progression. Mod Pathol 2020;33(11):2128-38. https://doi.org/10.1038/s41379-020-0603-3
- Footnote 5
-
Radia T, Williams N, Agrawal P, Harman K, Weale J, Cook J, Gupta A. Multi-system inflammatory syndrome in children & adolescents (MIS-C): a systematic review of clinical features and presentation. Paediatr Respir Rev 2020;S1526-0542(20)30117-2. https://doi.org/10.1016/j.prrv.2020.08.001
- Footnote 6
-
Boudhabhay I, Rabant M, Coupry L-M, Marchal A, Lubka TR, El-Karoui K, Monchi M, Pourcine F. Adult post COVID-19 multisystem inflammatory syndrome and thrombotic microangiopathy. Preprint. Research Square; (updated 2020-09-16; accessed 2020-05-29). https://doi.org/10.21203/rs.3.rs-76310/v1
- Footnote 7
-
Chowdhary A, Joy E, Plein S, Abdel-Rahman SE. Multisystem inflammatory syndrome in an adult with SARS-CoV-2 infection. Eur Heart J Cardiovasc Imaging 2021;22(5):e17. https://doi.org/10.1093/ehjci/jeaa232
- Footnote 8
-
Jones I, Bell LC, Manson JJ, Last A; UCLH COVID Response Team. An adult presentation consistent with PIMS-TS. Lancet Rheumatol 2020;2(9):e520–1. https://doi.org/10.1016/S2665-9913(20)30234-4
- Footnote 9
-
Lidder AK, Pandit SA, Lazzaro DR. An adult with COVID-19 kawasaki-like syndrome and ocular manifestations. Am J Ophthalmol Case Rep 2020;20:100875. https://doi.org/10.1016/j.ajoc.2020.100875
- Footnote 10
-
Moghadam P, Blum L, Ahouach B, Radjou A, Lambert C, Scanvic A, Martres P, Decalf V, Bégon E, Bachmeyer C. Multisystem inflammatory syndrome with particular cutaneous lesions related to COVID-19 in a young adult. Am J Med 2021;134(1):e36–7. https://doi.org/10.1016/j.amjmed.2020.06.025
- Footnote 11
-
Shaigany S, Gnirke M, Guttmann A, Chong H, Meehan S, Raabe V, Louie E, Solitar B, Femia A. An adult with Kawasaki-like multisystem inflammatory syndrome associated with COVID-19. Lancet 2020;396(10246):e8–10. https://doi.org/10.1016/S0140-6736(20)31526-9
- Footnote 12
-
Fox SE, Lameira FS, Rinker EB, Vander Heide RS. Cardiac endotheliitis and multisystem inflammatory syndrome after COVID-19. Ann Intern Med 2020;173(12):1025–7. https://doi.org/10.7326/L20-0882
- Footnote 13
-
Sokolovsky S, Soni P, Hoffman T, Kahn P, Scheers-Masters J. COVID-19 associated Kawasaki-like multisystem inflammatory disease in an adult. Am J Emerg Med 2021;39(39):253.e1–2. https://doi.org/10.1016/j.ajem.2020.06.053
- Footnote 14
-
Kofman AD, Sizemore EK, Detelich JF, Albrecht B, Piantadosi AL. A young adult with COVID-19 and multisystem inflammatory syndrome in children (MIS-C)-like illness: a case report. BMC Infect Dis 2020;20(1):716. https://doi.org/10.1186/s12879-020-05439-z
- Footnote 15
-
Stankovic K, Miailhes P, Bessis D, Ferry T, Broussolle C, Sève P. Kawasaki-like syndromes in HIV-infected adults. J Infect 2007;55(6):488–94. https://doi.org/10.1016/j.jinf.2007.09.005
- Footnote 16
-
Whittaker E, Bamford A, Kenny J, Kaforou M, Jones CE, Shah P, Ramnarayan P, Fraisse A, Miller O, Davies P, Kucera F, Brierley J, McDougall M, Carter M, Tremoulet A, Shimizu C, Herberg J, Burns JC, Lyall H, Levin M; 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(3):259–69. https://doi.org/10.1001/jama.2020.10369
- Footnote 17
-
Mahase E. Covid-19: cases of inflammatory syndrome in children surge after urgent alert. BMJ 2020;369:m1990. https://doi.org/10.1136/bmj.m1990
- Footnote 18
-
Drago F, Javor S, Ciccarese G, Cozzani E, Parodi A. A case of complete adult-onset Kawasaki disease: a review of pathogenesis and classification. Dermatology 2015;231(1):5–8. https://doi.org/10.1159/000381911
- Footnote 19
-
Morris SB, Schwartz NG, Patel P, Abbo L, Beauchamps L, Balan S, Lee EH, Paneth-Pollak R, Geevarughese A, Lash MK, Dorsinville MS, Ballen V, Eiras DP, Newton-Cheh C, Smith E, Robinson S, Stogsdill P, Lim S, Fox SE, Richardson G, Hand J, Oliver NT, Kofman A, Bryant B, Ende Z, Datta D, Belay E, Godfred-Cato S. 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 2020;69(40):1450–6. https://doi.org/10.15585/mmwr.mm6940e1
- Footnote 20
-
Son MB, Friedman K. COVID-19: Multisystem inflammatory syndrome in children (MIS-C) management and outcome: features of Kawasaki disease. Alphen aan den Rijn (NL): Wolters Kluwer; (updated 2021; accessed 2021-03-25). https://www.uptodate.com/contents/covid-19-multisystem-inflammatory-syndrome-in-children-mis-c-management-and-outcome?search=COVID%2019%20multi%20inflammatory%20response&topicRef=128389&source=see_link#H1902242396
- Footnote 21
-
Tenforde MW, Morris SB. Multisystem inflammatory syndrome in adults: coming into focus. Chest 2021;159(2):471–2. https://doi.org/10.1016/j.chest.2020.09.097
- Footnote 22
-
World Health Organization. Multisystem inflammatory syndrome in children and adolescents temporally related to COVID-19: scientific brief. Geneva: WHO; (updated 2020-05-15; accessed 2020-12-14). https://www.who.int/news-room/commentaries/detail/multisystem-inflammatory-syndrome-in-children-and-adolescents-with-covid-19
- Footnote 23
-
Centers for Disease Control. Information for healthcare providers about multisystem inflammatory syndrome in children (MIS-C). Atlanta (GA): CDC; (updated 2020; accessed 2020-12-14). https://www.cdc.gov/mis-c/hcp/
- Footnote 24
-
Royal College of Paediatrics and Child Health. Paediatric multisystem inflammatory syndrome temporally associated with COVID-19 (PIMS) - guidance for clinicians. London (UK): RCPCH; (updated 2020; accessed 2020-12-06). https://www.rcpch.ac.uk/resources/paediatric-multisystem-inflammatory-syndrome-temporally-associated-covid-19-pims-guidance
- Footnote 25
-
Berard RA, Tam H, Scuccimarri R, Haddad E, Morin MP, Chan KJ, Dahdah NS, McCrindle BW, Price VE, Yeung RS, Laxer RM. Acute Care Committee Paediatric inflammatory multisystem syndrome temporally associated with COVID-19. Ottawa (ON): Canadian Pediatric Society; (updated 2020-07-06; accessed 2020-12-14). https://www.cps.ca/documents/position/pims
Appendices
Patient/studies characteristics |
Boudhabhay et al., 2020Footnote 6 | Chowdhary et al., 2021Footnote 7 | Fox et al., 2020Footnote 12 | Jones et al., 2020Footnote 8 | Kofman 2020Footnote 14 | Lidder et al., 2020Footnote 9 | Moghadam et al., 2020Footnote 10 | Sokolovsky et al., 2020Footnote 13 | Shaigany et al., 2020Footnote 11 | |
---|---|---|---|---|---|---|---|---|---|---|
Background | Ethnicity | African | NR | African American | African | NR | NR | White | Hispanic | Hispanic |
Age, years | 46 | 26 | 31 | 21 | 25 | 45 | 21 | 36 | 45 | |
Sex | Male | Male | Female | Male | Female | Male | Male | Female | Male | |
Presence of comorbidity | X | NR | X | NR | – | – | NR | – | – | |
Symptoms and system/organ involved | Fever | X | X | X | X | – | X | X | X | X |
Cardiovascular | X | X | X | – | X | X | X | X | X | |
Digestive | – | X | X | – | X | X | X | X | X | |
Ophthalmic | – | – | – | X | X | X | X | X | X | |
Renal | X | – | X | – | X | – | – | – | X | |
Dermatologic | X | – | – | X | – | X | X | X | – | |
Pulmonary | – | X | X | – | – | – | – | – | – | |
Neurologic | X | – | – | – | – | – | – | – | – | |
RT-PCR and serology test results | RT-PCR | Negative | Negative | Negative | Negative | Positive | Positive | Negative | Negative | Positive |
Serology | Positive | Positive | NR | Positive | Positive | NR | Positive | Positive | NR | |
Elevated inflammatory markers and lymphopenia | CRP | X | X | X | NR | X | X | X | X | X |
Troponin | X | X | NR | X | – | X | X | NR | X | |
D-dimers | NR | X | X | NR | X | X | NR | X | X | |
Lymphopenia | NR | X | X | X | X | X | – | – | X | |
Exclusion of other infective and inflammatory conditions | NR | NR | NR | X | NR | X | X | X | X | |
Treatment | Immunoglobulin | – | – | – | X | X | X | – | – | X |
Prednisolone | – | – | – | X | – | X | – | X | – | |
Aspirin | – | X | – | – | X | – | – | X | – | |
Outcome | Recovery | Recovery | Death | Recovery | Recovery | NR | Recovery | Recovery | Recovery | |
Case report/demographic characteristics and past medical history | MIS-A clinical and laboratory characteristics | Treatment/severity and outcome |
---|---|---|
Boudhabhay et al., 2020Footnote 6 |
Fever and other signs and symptoms:
Evidence of coagulopathy and renal involvement:
PCR and serology for SARS-CoV-2:
Inflammatory markers:
|
The patient was discharged after 30 days in hospital |
Chowdhary et al., 2021Footnote 7 |
Fever and other signs and symptoms:
One or more organs involved (pulmonary, cardiac, digestive):
PCR and serology for SARS-CoV-2:
Inflammatory markers:
|
The patient was admitted to the ICU and recovered over 10 days. |
Fox et al., 2020Footnote 12 |
The patient was admitted for sudden fever 39.8ºC (duration not specified), tachycardia (120 beats/min), left-sided neck pain, nausea and vomiting
One or more organs involved (pulmonary, cardiac, parotids, renal):
PCR and serology for SARS-CoV-2:
|
Patient developed hemodynamic instability and ventricular fibrillation during evaluation for hospital admission and died. |
Jones et al., 2020Footnote 8 |
Fever and other signs or symptoms:
PCR and serology for SARS-CoV-2:
One or more organs involved:
Inflammatory markers:
|
The patient was discharged after a length of hospital stay of eight days. |
Kofman et al., 2020Footnote 14 |
Fever and other signs and symptoms:
Upon admission:
One or more organs involved (renal, cardiac, digestive, ocular):
PCR and serology for SARS-CoV-2:
Inflammatory markers:
|
The patient was admitted to the ICU twice during her hospital stay. She was discharged on Day 5. |
Lidder et al., 2020Footnote 9 |
Fever and other signs and symptoms:
One or more organs involved (renal, cardiac, digestive, ophthalmologic):
Excluding other cause:
PCR and serology for SARS-CoV-2:
Inflammatory markers:
|
The length of hospital stay was not reported, but the patient did not demonstrate shock-like signs. |
Moghadam et al., 2020Footnote 10 |
Fever and other signs and symptoms:
One or more organs involved (cardiac, digestive, pleural):
PCR and serology for SARS-CoV-2:
Inflammatory markers:
Exclusion of other causes:
|
The patient stayed in the ICU for eight days and recovered. |
Sokolovsky et al., 2020Footnote 13 |
Fever and other signs and symptoms:
One or more organs involved (cardiac, digestive):
PCR and serology for SARS-CoV-2:
Inflammatory markers:
Exclusion of other cause:
|
The patient stayed at least six days in hospital and recovered. |
Shaigany et al., 2020Footnote 11 |
Fever and other signs and symptoms:
One or more organs involved (renal, cardiac, digestive, ophthalmologic):
PCR and serology for SARS-CoV-2:
Inflammatory markers:
Exclusion of other causes:
|
The patient was in hospital for eight days and did not require vasopressor support or ICU level of care, and recovered. |
Authors | Definitions of MIS-C | |
---|---|---|
World Health Organization (WHO)Footnote 22 | Diagnosis of MIS-C in children and adolescents aged less than 19 years includes a positive COVID-19 test or likely contact with COVID-19-positive individuals and several signs and symptoms. These include fever lasting for more than three days and two of the following:
|
|
Centers for Disease Control (CDC)Footnote 23 | An individual below the age of 21 years presenting with fever lasting for more than 24 hours and laboratory evidence of inflammation, such as an elevated CRP, ESR, fibrinogen, procalcitonin, D-dimer, ferritin, lactic acid dehydrogenase (LDH) or interleukin-6, elevated neutrophils, reduced lymphocytes and low albumin. The patient must also have an evidence of clinically severe illness requiring hospitalization, with multisystem organ involvement and no alternative plausible diagnoses. The patient must be positive for current or recent SARS-CoV-2 infection by RT-PCR, serology or antigen test; or must have been exposed to a suspected or confirmed COVID-19 case within the four weeks prior to the onset of symptoms. | |
Royal College of Paediatrics and Child Health (RCPCH)Footnote 24 | A child presenting with persistent fever, inflammation (neutrophilia, elevated CRP and lymphopenia) and evidence of single or multi-organ dysfunction (shock, cardiac, respiratory, renal, gastrointestinal or neurologic disorder) with persistent fever over 38.5°C most of the time, oxygen requirement, hypotension and other features. The laboratory tests must show abnormal fibrinogen, absence of potential causative organisms (other than SARS-CoV-2), high CRP, high D-dimers, high ferritin, hypoalbuminemia and/or lymphopenia. This may include children fulfilling full or partial criteria for Kawasaki disease. Any other microbial cause, including bacterial sepsis, staphylococcal or streptococcal shock syndromes, infections associated with myocarditis such as enterovirus must be excluded. The SARS-CoV-2 PCR testing may be positive or negative. | |
Canadian Pediatric Society (CPS)Footnote 25 | The presence of high and persistent fever (≥3 days) unexplained by other causes. Fever together with laboratory evidence of marked systemic inflammation and temporal association with COVID-19 having been present in the community should raise the index of suspicion for MIS-C. The clinical presentations described to date have included fever with hyperinflammation; a Kawasaki-like syndrome; and shock or toxic shock-like states, with signs of hypotension and poor perfusion related to severe myocardial dysfunction. Gastrointestinal distress, that may or may not occur with neurologic signs such as neck stiffness, altered mental status or lethargy. | |
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