#15,482
Since late April we've been following a rare, but very serious, complication of SARS-CoV-2 infection in children and adolescents which has been dubbed (in the U.S.) MIS-C (Multisystem Inflammatory Syndrome in Children).
The CDC describes the syndrome on their MIS-C website as:
What is MIS-C?
Multisystem inflammatory syndrome in children (MIS-C) is a condition where different body parts can become inflamed, including the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal organs. Children with MIS-C may have a fever and various symptoms, including abdominal (gut) pain, vomiting, diarrhea, neck pain, rash, bloodshot eyes, or feeling extra tired. We do not yet know what causes MIS-C. However, many children with MIS-C had the virus that causes COVID-19, or had been around someone with COVID-19.
Last Monday, in CHOP Research: COVID-linked MIS-C Associated with Myocardial Injury, we looked at research suggesting that children may sustain subtle cardiac damage from this syndrome, not unlike what we've seen reported in some adults with COVID-19 (see JAMA: Two Studies Linking SARS-CoV-2 Infection To Cardiac Injury).
Over the summer we've seen a smattering of reports of `Kawasaki-like illness' - similar to MIS-C - in adults with SARS-CoV-2 infection, raising questions over whether a similar syndrome may be impacting COVID-19 cases of all ages.
A couple of examples include:
An adult with Kawasaki-like multisystem inflammatory syndrome associated with COVID-19
Sheila Shaigany Marlis Gnirke Allison Guttmann Hong Chong Shane Meehan Vanessa Raabe et al.
July 10, 2020 THE LANCET DOI: https://doi.org/10.1016/S0140-6736(20)31526-9
COVID-19 associated Kawasaki-like multisystem Inflammatory disease in an adult
Sabrina Sokolovsky, DO,a Parita Soni, MD,b Taryn Hoffman, MD,a Philip Kahn, MD,c and Joshua Scheers-Masters, MDd,⁎
Am J Emerg Med. 2020 Jun 25 doi: 10.1016/j.ajem.2020.06.053
All of which brings us to a new MMWR Early Release, published yesterday, which presents a case series on a number of adult patients in the UK and the United States presenting with a Multi-System Inflammatory Syndrome (MIS-A) associated with SARS-CoV-2 infection.
Due to its length, I've only included the link, summary, and some excerpts from the discussion. Follow the link to read it in its entirety. I'll have a brief postscript when you return.
Case Series of Multisystem Inflammatory Syndrome in Adults Associated with SARS-CoV-2 Infection — United Kingdom and United States, March–August 2020
Early Release / October 2, 2020 / 69
Sapna Bamrah Morris, MD1; Noah G. Schwartz, MD1,2; Pragna Patel, MD1; Lilian Abbo, MD3; Laura Beauchamps, MD3; Shuba Balan, MD3; Ellen H. Lee, MD4; Rachel Paneth-Pollak, MD4; Anita Geevarughese, MD4; Maura K. Lash, MPH4; Marie S. Dorsinville, MPH4; Vennus Ballen, MD4; Daniel P. Eiras, MD4; Christopher Newton-Cheh, MD5,6; Emer Smith, MPH7,8; Sara Robinson, MPH7; Patricia Stogsdill, MD9; Sarah Lim, MBBCh10; Sharon E. Fox, MD, PhD11,12; Gillian Richardson, MPH13; Julie Hand, MSPH13; Nora T. Oliver, MD14; Aaron Kofman, MD15; Bobbi Bryant, MPH1,16; Zachary Ende, PhD1,16; Deblina Datta, MD1; Ermias Belay, MD1; Shana Godfred-Cato, DO1 (View author affiliations)View suggested citation
Summary
What is already known about this topic?
Multisystem inflammatory syndrome in children (MIS-C) is a rare but severe complication of SARS-CoV-2 infection in children and adolescents. Since June 2020, several case reports and series have been published reporting a similar multisystem inflammatory syndrome in adults (MIS-A).
What is added by this report?
Cases reported to CDC and published case reports and series identify MIS-A in adults, who usually require intensive care and can have fatal outcomes. Antibody testing was required to identify SARS-CoV-2 infection in approximately one third of 27 cases.
What are the implications for public health practice?
Clinical suspicion and indicated SARS-CoV-2 testing, including antibody testing, might be needed to recognize and treat adults with MIS-A. Further research is needed to understand the pathogenesis and long-term effects of this condition. Ultimately, the recognition of MIS-A reinforces the need for prevention efforts to limit spread of SARS-CoV-2.
(SNIP)
Discussion
Findings indicate that adult patients of all ages with current or previous SARS-CoV-2 infection can develop a hyperinflammatory syndrome resembling MIS-C. Although hyperinflammation and extrapulmonary organ dysfunction have been described in hospitalized adults with severe COVID-19, these conditions are generally accompanied by respiratory failure (7). In contrast, the patients described here had minimal respiratory symptoms, hypoxemia, or radiographic abnormalities in accordance with the working case definition, which was meant to distinguish MIS-A from severe COVID-19; only eight of 16 patients had any documented respiratory symptoms before onset of MIS-A.
The pathophysiology of MIS in both children and adults is currently unknown. Eight of 27 (30%) adults described in this report and 45% of 440 children with MIS-C reported to CDC through July 29, 2020, (1) had negative PCR and positive SARS-CoV-2 antibody test results, suggesting MIS-A and MIS-C might represent postinfectious processes. However, in some patients, persistent infection outside the upper respiratory tract is possible; SARS-CoV-2 has been identified in multiple organs including the heart, liver, brain, kidneys, and gastrointestinal tract (7). Additional proposed mechanisms for extrapulmonary dysfunction in COVID-19 include endothelial damage and thromboinflammation, dysregulated immune responses, and dysregulation of the renin-angiotensin-aldosterone system (7).The interval between infection and development of MIS-A is unclear, adding to uncertainty regarding whether MIS-A represents a manifestation of acute infection or an entirely postacute phenomenon. In patients with COVID-19, dyspnea is typically experienced a median of 5–8 days and critical illness 10–12 days after onset of symptoms.§ In patients who reported typical COVID-19 symptoms before MIS-A onset, MIS-A was experienced approximately 2–5 weeks later. However, eight MIS-A patients reported no preceding respiratory symptoms, making it difficult to estimate when initial infection occurred.Given the high proportion of MIS-C patients with negative PCR testing, clinical guidelines recommend the use of both antibody and viral testing to assist with diagnosis (8–10). In patients with atypical or late manifestations of SARS-CoV-2 infection, including MIS-A, positive antibody results might be crucial to augment clinical recognition of this condition and guide treatment. In addition, the use of a panel of laboratory tests for inflammation, hypercoagulability, and organ damage (e.g., CRP, ferritin, D-dimer, cardiac enzymes, liver enzymes, and creatinine) might assist in the early identification and management of this COVID-19–associated condition.All but one of the patients with MIS-A described in this report belonged to racial or ethnic minority groups. Long-standing health and social inequities have resulted in increased risk for infection and severe outcomes from COVID-19 in communities of color.¶ MIS-C has also been reported disproportionately in these communities (1). Because patients described in this review represent a convenience sample from a small number of jurisdictions, conclusions cannot be made regarding the true burden or determinants of MIS-A in different groups; further research is needed.The majority (24 of 27) of patients with MIS-A survived, similar to those with MIS-C, associated with receiving care in acute, often intensive, health care settings. Because of the potential therapies that might benefit these patients as described in these case reports, clinicians should consider MIS-A within a broader differential diagnosis when caring for adult patients with clinical and laboratory findings consistent with the working MIS-A case definition.
- An individual aged <21 years presenting with fever i, laboratory evidence of inflammation ii, and evidence of clinically severe illness requiring hospitalization, with multisystem (>2) organ involvement (cardiac, renal, respiratory, hematologic, gastrointestinal, dermatologic or neurological); AND
- No alternative plausible diagnoses; AND
- Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or COVID-19 exposure within the 4 weeks prior to the onset of symptoms
i Fever >38.0°C for ≥24 hours, or report of subjective fever lasting ≥24 hours
ii Including, but not limited to, one or more of the following: an elevated C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, procalcitonin, d-dimer, ferritin, lactic acid dehydrogenase (LDH), or interleukin 6 (IL-6), elevated neutrophils, reduced lymphocytes and low albumin
Additional comments
- Some individuals may fulfill full or partial criteria for Kawasaki disease but should be reported if they meet the case definition for MIS-C
- Consider MIS-C in any pediatric death with evidence of SARS-CoV-2 infection
Which means we are probably under-counting cases across all age groups.
While most COVID-19 related deaths occur in the elderly, increasingly we are seeing reports of younger adults and children with lingering - and sometimes even permanent - sequelae from SARS-CoV-2 infection (PAHO Epi Alert: Complications & Sequelae Of COVID-19).
Making this an infection - regardless of your age and overall health - you would really do well to avoid.
