MIS-Children and MIS-Adults were first recognized as a serious sequela to COVID-19.  It is a poorly understood, underreported, hyperinflammation of multiple organ systems following COVID infection.  It is often not diagnosed in a timely manner. 

MIS is defined as:

  1. Individual presenting with fever
  2. Laboratory evidence of inflammation
  3. Clinically severe illness with multisystem organ involvement 
  4. AND evidence of recent COVID infection and/or vaccination.

The CDC recently published a report on MIS in children 12-20 following COVID vaccination. https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(22)00028-1/fulltext


Many reports of MIS following vaccination have begun to emerge as well.

Multisystem inflammatory syndrome in an adult following Pfizer (MIS-V): https://pubmed.ncbi.nlm.nih.gov/34326117/
Multisystem inflammatory syndrome in a 12yo male following Pfizer: https://pubmed.ncbi.nlm.nih.gov/34978781/
Multisystem inflammatory Syndrome in a 12 year old boy after Pfizer: https://pubmed.ncbi.nlm.nih.gov/34955518/
3 cases of Multisystem Inflammatory Syndrome after Pfizer: https://pubmed.ncbi.nlm.nih.gov/34034858/
Multisystem Inflammation in a 20yoM following Pfizer: https://pubmed.ncbi.nlm.nih.gov/34765984/
MIS-A in a 21yoF following Moderna vaccination which was given 27 days after COVID infection:https://pubmed.ncbi.nlm.nih.gov/34954311/
MIS-A in a 37yoF 10 days post 2nd Moderna COVID vaccine and 1 month from COVID infection:https://pubmed.ncbi.nlm.nih.gov/34868588/
Multisystem inflammatory syndrome in children by covid-19 vaccination of adolescents in France: https://pubmed.ncbi.nlm.nih.gov/34928295/
Multisystem inflammatory syndrome in a COVID-19 vaccinated adolescent female with sickle cell disease: https://pubmed.ncbi.nlm.nih.gov/34955521/
Autoantibody release in children after COVID mRNA vaccination: A risk factor of multisystem inflammatory syndrome? https://pubmed.ncbi.nlm.nih.gov/34835284/
Multisystem inflammatory syndrome following COVID-19 vaccination: ignored and underdiagnosed: https://pubmed.ncbi.nlm.nih.gov/34940858/
Postmortem investigation of fatalities following vaccination with COVID-19 vaccines: https://pubmed.ncbi.nlm.nih.gov/34591186/
Autopsy findings and causality relationship between death and covid-19 vaccination: a systematic review: https://pubmed.ncbi.nlm.nih.gov/34945172/
MIS-C in a a male adolescent after his second dose of Pfizer: https://pubmed.ncbi.nlm.nih.gov/34617315/
Multisystem inflammatory syndrome in an adult following AstraZeneca: https://pubmed.ncbi.nlm.nih.gov/34811978/
Postvaccination MIS in an adult with no evidence of prior COVID-19 infection following AstraZeneca: https://pubmed.ncbi.nlm.nih.gov/34852213/
Hyper-inflammation after COVID-19 mRNA vaccination: at the cross roads of multi-inflammatory disease and adult onset still’s disease


MIS-A in an adult woman 18 days following AstraZeneca vaccination: https://pubmed.ncbi.nlm.nih.gov/34511054/
Fatal Multisystem inflammatory syndrome after 2nd dose of Pfizer: https://pubmed.ncbi.nlm.nih.gov/34586059/

The CDC Published a MIS-Associated with COVID report form: https://stacks.cdc.gov/view/cdc/88583


Going down the checklist, COVID long haulers and the COVID vaccine injured often find themselves meeting the criteria for MIS diagnosis, the exception being the vaccine injured without prior COVID infection. Multiple organ system involvement and laboratory evidence of systemic inflammation are the hallmarks of MIS.

MIS has been postulated to involve a dysregulated immune response. Studies are attempting to understand the pathophysiology of MIS and weather endotheliitis, autoimmune and/or other mechanisms are responsible for hyperinflammation.


Most patients with MIS presented with fever (96%), hypotension (60%), cardiac dysfunction (54%), shortness of breath (52%) and diarrhea (52%)

Affected organ systems are hematologic, cardiovascular, gastrointestinal, and respiratory. 

Myocarditis was diagnosed in 30% and cardiac dysfunction in 54% of the reviewed MIS cases.

Early and appropriate diagnosis of MIS events is essential for definite therapy.

Treatment of MIS includes; corticosteroids, intravenous immunoglobulin (IVIG), anticoagulants and immune modulators. Early treatment is essential to reduce tissue damage and improve patient outcome.  

 A high index of suspicion must be kept for MIS-V and COVID-19 vaccine related myocarditis to reduce morbidity and have a favorable outcome.


Proposed mechanism of MIS, COVID spike protein initiates cascade of events leading to hyperinflammatory syndrome

The autopsy of two adolescents who died of myocarditis following the second dose of COVID vaccine https://pubmed.ncbi.nlm.nih.gov/35157759/ has revealed that the type of myocarditis caused by vaccines is consistent with “catecholamine-induced injury, not typical myocarditis pathology”



The heart damage seen is consistent with MIS-C caused heart inflammation


The authors reference and discuss the autopsy and biopsy of two adult cases of myocarditis post vaccination. The findings are the same. The injury appears to be due to hyperinflammation rather than typical myocardial injury. 


The same inflammatory mechanisms appear to be at play in both COVID and vaccine induced MIS, indeed, the observed increase in myocarditis and pericarditis post COVID vaccine may be due to the same MIS causing mechanisms. 


Early recognition and treatment is key. Steroids should be employed early and supported with IVIG and additional therapies as required. Clinicians must be aware, diligent and exercise prudence in recognizing clinical and laboratory findings suggestive of MIS diagnosis and be proactive in treating suspected cases.