DOCTORS with patients presenting with fever, particularly with rash or red eyes, with gastrointestinal symptoms, or even shock, should keep multisystem inflammatory syndrome (MIS) in mind, even if the patient says they have not had COVID-19, experts say.

MIS has been well described in children (MIS-C) since the COVID-19 pandemic began, with two in 100 000 children affected during the 2020 COVID-19 outbreak in New York.

It’s now understood that COVID-19 can also trigger MIS in adults (called MIS-A), which can occur up to 12 weeks after primary infection.

A paper published by the MJA presents two complex cases of MIS-A in New South Wales when the Delta strain was dominant.

In both cases, the patients were young, with mostly mild or no underlying medical conditions when they were diagnosed with a SARS-CoV-2 infection. What makes the cases unusual is both patients had also been vaccinated in the weeks following their acute SARS-CoV-2 infection and their MIS developed 8 hours and 7 days after vaccination, respectively.

One of the paper’s authors, Dr Jamma Li, told InSight+ that because MIS-A after COVID-19 was so rare, it’s hard to know what caused it.

“We know it’s from excessive inflammation in the body. And viruses or other infections can trigger inflammation. So can the COVID-19 vaccine and the two of them combined. In the literature, there are definitely more case reports of MIS from COVID-19 infection, rather than the vaccine itself,” she explained.

Dr Annaleise Howard-Jones, an infectious diseases and microbiology registrar at New South Wales Health pathology, agreed that it was hard to determine what role the vaccine had in these particular cases.

“At the moment, there aren’t enough cases to be definitive about whether the vaccine has a role to play in either causing the condition or exacerbating the condition, or whether it’s just a coincidental finding that the vaccination was given during that intervening period,” she told InSight+.

Dr Howard-Jones wrote in the MJA earlier in 2022 to highlight an Australian case of MIS-A during the 2021 SARS‐CoV‐2 Delta outbreak.

“The good news from the vaccination point of view is that we have very few cases of MIS-A in Australia and very few in the context of a COVID-19 vaccination having been given. We have given over 50 million vaccination doses in Australia to date. And we’ve got here two cases of MIS-A, which may or may not have been associated with the vaccine. So those kinds of numbers are very reassuring, particularly when you consider the number of severe cases of COVID-19,” she highlighted.

MIS has, as the name makes clear, multisystem involvement, so symptoms can vary. According to the US Centers for Disease Control and Prevention (CDC), clinical criteria include fever, severe cardiac illness, rash and conjunctivitis.

“The laboratory test results will be quite abnormal, particularly in terms of inflammation markers, like the C-reactive protein or the erythrocyte sedimentation rate. But depending on what organ is involved for the patient, (doctors) can have a look for blood count, abnormal kidney function, and abnormal liver function,” Dr Li said.

Dr Howard-Jones said although it’s rare, it’s important that emergency doctors and GPs are aware of the condition.

“[Look out for] patients presenting with fever, particularly with rash or red eyes with gastrointestinal symptoms, or in more severe cases with shock,” she highlighted.

It’s important to consider MIS-A even when patients don’t report a previous SARS-CoV-2 infection, she said. There’s potential that the person didn’t experience symptoms and didn’t know they’d been infected.

“There are many cases reported of MIS-A or MIS-C, where the patient doesn’t recall a COVID-19-related illness or they had no symptoms at the time, but they may have been exposed. Any patient that’s presenting with these kinds of symptoms, it should be considered whether or not they had a confirmed COVID diagnosis in the preceding month,” Dr Howard-Jones said.

It’s also comforting to know that MIS may be less frequent with the Omicron variant, although it’s too early to confirm definitively.

“The (Omicron) infection is different,” said Dr Li.

“Also the vaccine is not as targeted against Omicron as against previous variants. So, the immune response is probably not to the same amplitude.”

For GPs advising patients about vaccination after SARS-CoV-2 infection, it’s important to follow the Australian Technical Advisory Group on Immunisation (ATAGI) advice. The current advice for people who have been infected with the COVID-19 virus is that there is no requirement to delay vaccination as long as the acute infection has passed; however, it can be deferred for up to 4 months

“Always follow the most up to date guidance from ATAGI, who are considering these cases and all the feedback on vaccination efficacy and vaccination adverse events. That’s all being fed in real-time into the target recommendations,” Dr Howard-Jones concluded.

Also online first at

Perspective: COVID‐19 vaccines, boosters and mandates: building a mission economy, not a rentier paradise
Hensher and Dona; doi: 10.5694/mja2.51500OPEN ACCESS permanently

Podcast: Professor Martin Hensher, Henry Baldwin Professorial Research Fellow in Health System Sustainability at the Menzies Institute for Medical Research … FREE ACCESS permanently

Research: A general practice intervention for people at risk of poor health outcomes: the Flinders QUEST cluster randomised controlled trial and economic evaluation
Reed et al; doi: 10.5694/mja2.51484OPEN ACCESS permanently

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