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Inflammatory syndrome linked to SARS-CoV-2 can affect adults

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On 15 May, the World Health Organization developed a preliminary case definition for multisystem inflammatory syndrome in children (MIS-C), a newly described childhood syndrome linked to SARS-CoV-2.
 
MIS-C is also known as paediatric inflammatory multisystem syndrome temporally (PIMS-TS). It is associated with SARS-CoV-2 and the official case definition includes an age limit of 20.
 
The Centers for Disease Control and Prevention (CDC) in the US has now reported on a similar condition, multisystem inflammatory syndrome in adults (MIS-A).
 
‘Findings indicate that adult patients of all ages with current or previous SARS-CoV-2 infection can develop a hyperinflammatory syndrome resembling MIS-C,’ the authors wrote.
 
‘Although hyperinflammation and extrapulmonary organ dysfunction have been described in hospitalised adults with severe COVID-19, these conditions are generally accompanied by respiratory failure.
 
‘In contrast, the patients described here had minimal respiratory symptoms, hypoxaemia, or radiographic abnormalities in accordance with the working case definition, which was meant to distinguish MIS-A from severe COVID-19.’
 
The authors say this might need to be revised, but for now the working MIS-A case definition includes the following criteria:

• A severe illness requiring hospitalisation in a person aged ≥21 years
• A positive test result for current or previous SARS-CoV-2 infection (nucleic acid, antigen, or antibody) during admission or in the previous 12 weeks
• Severe dysfunction of one or more extrapulmonary organ systems (eg hypotension or shock, cardiac dysfunction, arterial or venous thrombosis or thromboembolism, or acute liver injury)
• Laboratory evidence of severe inflammation (eg elevated C-reactive protein, ferritin, D-dimer, or interleukin-6)
• Absence of severe respiratory illness (to exclude patients in which inflammation and organ dysfunction might be attributable simply to tissue hypoxia)

The CDC notes that ‘several case reports’ of a similar syndrome to MIS-C in adults have been described since June 2020.
 
The CDC report examines a case series of 27 patients from the US and UK who had a range of symptoms – such as cardiovascular, gastrointestinal, dermatologic, and neurologic – but importantly did not have severe respiratory illness.
 
Sixteen cases are described in detail, including nine which were officially reported to the CDC and seven described in published case reports. Patients’ ages ranged from 21–50.
 
All patients had either a positive COVID-19 or antibody test.
 
Ten patients required treatment in the intensive care unit (ICU), and two died.
 
The authors note that 30% of adults described in the report and 45% of 440 children with MIS-C reported to CDC up to July 2020 had negative polymerase chain reaction (PCR) and positive SARS-CoV-2 antibody tests, suggesting both syndromes might represent post-infectious processes.
 
However, the interval between infection and development of MIS-A is ‘unclear’.
 
‘[That adds] to uncertainty regarding whether MIS-A represents a manifestation of acute infection or an entirely post-acute phenomenon,’ the authors wrote.
 
Professor David Burgner is a paediatric infectious diseases clinician scientist at the Murdoch Children’s Research Institute (MCRI) who has been working with Safer Care Victoria on PIMS-TS. He is also medical advisor to the Kawasaki Disease Foundation Australia.
 
He told newsGP he was not surprised to hear the CDC has now identified a multisystem inflammatory syndrome affecting adults, especially considering those mentioned in the review were aged between 20 and 50.
 
‘It’s not that surprising because PIMS-TS/MIS-C occurs in mid to late childhood into adolescence, so you might expect some younger adults to have a similar syndrome,’ Professor Burgner said.
 
He says MIS-A shares a lot of similarity with MIS-C, including epidemiologically, with both conditions affecting minority groups disproportionately.
 
All but one of the patients with MIS-A described in the CDC report belonged to racial or ethnic minority groups.
 
‘MIS-C has also been reported disproportionately in these communities,’ the authors wrote.


Professor David Burgner says this newly described hyperinflammatory syndrome is likely to be rare.

Professor Burgner says the risk factors for patients developing PIMS-TS/MIS-C and MIS-A are also similar, with obesity playing a key role in development of both conditions. The cause of these conditions is also unknown.
 
Furthermore, Professor Burgner says, management of both conditions is ‘pretty much the same’. He says they also both appear to be post-infectious phenomena, though that is not entirely clear at this stage.
 
The CDC authors say that in patients who reported typical COVID-19 symptoms before onset of MIS-A, it 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,’ the authors wrote.
 
While Professor Burgner agrees with the authors that COVID-19 can create inflammatory effects, he believes MIS-A is a distinct entity from acute infection.
 
‘Some of the features of the acute COVID-19 illness do involve inflammation and coagulation, but this does seem distinct in terms of the myocardial effects and the marked inflammation,’ he said.
 
‘[MIS-A] does seem to be a separate entity.’
 
After defining this newly described syndrome, the authors advise that clinicians and health departments consider MIS-A in adults with ‘compatible signs and symptoms’.
 
Professor Burgner agrees with that advice.
 
‘If [a clinician] sees a patient – especially if there’s an epidemiological history of exposure or clinical history of previously having COVID-19 and it’s a few weeks afterwards and they’re presenting with abdominal features and fever – they should consider MIS-A, and they should seek urgent specialist advice,’ he said.
 
Professor Burgner is keen to note, however, this is unlikely to be a significant issue in Australia, considering the country’s low case numbers of COVID-19.
 
He says doctors in Australia may see ‘a case or two’ of MIS-A and that clinicians should remain aware of the condition, ‘but not alarmed’.
 
‘It appears to be very rare,’ Professor Burgner said. ‘Unless they’re missing a lot of cases, it’s even rarer than PIMS-TS/MIS-C.’
 
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COVID-19 MIS-A MIS-C multisystem inflammatory syndrome

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