multisystem inflammatory syndrome MIS

This patient presents with symptoms 3 weeks after a COVID-19 infection after initial resolution of symptoms. He has a rash, conjunctivitis, hypotension, and severely reduced left ventricular function at point-of-care ultrasonography; a markedly elevated C-reactive protein level; elevated lactate dehydrogenase, troponin, and lactate levels; and a normal chest radiograph and ECG. Clinicians should consider a diagnosis of multisystem inflammatory syndrome (MIS) among persons with hyperinflammatory illness and severe extrapulmonary multiorgan dysfunction, particularly cardiovascular, occurring within 2 to 5 weeks of antecedent COVID-19 infection (choice B is correct).

MIS is a severe hyperinflammatory condition occurring weeks after initial infection with many different disease phenotypes, including COVID-19 infection. Initially reported in children (MIS-C), it has also been described in adults (MIS-A), primarily affecting young, otherwise healthy persons. In the United States, male, Black, and Hispanic persons have been overrepresented among reported cases. MIS-A poses a greater diagnostic challenge than MIS-C does because of greater phenotypic overlap with acute COVID-19 and the presence of chronic medical conditions and therefore is likely significantly underrecognized.

Patients with MIS-A develop multiple organ system complications, particularly cardiovascular, with most developing cardiomyopathy, reduced left ventricular ejection fraction (LVEF), and myocardial injury; nearly one-half have a diagnosis of myocarditis. Results from several studies have suggested that in most patients with MIS-A with multiple LVEF measurements, LVEF normalized before discharge from the hospital. These results are similar to previous findings in MIS-C and MIS-A but unlike the natural history of cardiovascular manifestations of other diseases. These findings are likely in part attributable to a healthier patient population with fewer underlying health conditions but also suggest either a transient proinflammatory state or rapid reversibility with immunomodulatory agents.

A distinguishing feature of MIS-A and COVID-19 acute infection is the presence of a rash, which is much more common in MIS-A infection. Other distinguishing features are the presence of GI symptoms (particularly abdominal pain), conjunctival injection, fewer abnormalities on chest radiographs, and a greater degree of elevation in D-dimer and inflammatory laboratory markers, as seen in this patient. The timing of presentation is also important because MIS-A usually manifests 3 to 5 weeks after acute COVID-19 infection and usually after a period of recovery.

Patients with MIS-A present acutely ill, requiring ventilatory support and vasopressor support more often than do patients with acute COVID-19 infection. Treatment of MIS-A includes a combination of anticoagulants, corticosteroids, IV immunoglobulin, and immune modulators. These patients may also need mechanical circulatory support.

The patient had MIS-A diagnosed and was treated with IV immunoglobulins and immune modulators. He had a long hospital course and needed extracorporeal membrane oxygenation support but recovered and was discharged to a rehabilitation facility.

This is not long COVID infection because the patient had a period of recovery after acute COVID infection before developing these symptoms, and the inflammatory markers are very elevated (choice A is incorrect.) The National Institutes of Health uses the US Centers for Disease Control and Prevention definition of long COVID, which describes the condition as sequelae that extend beyond 4 weeks after initial infection. This can include fatigue, dyspnea, cardiovascular abnormalities, cognitive dysfunction, sleeplessness, olfactory and gustatory dysfunction, and acute kidney injury. It may be difficult to distinguish between long COVID and MIS-A in certain patients.

Pulmonary embolism is unlikely because the patient has left ventricular global dysfunction and the right ventricle appears normal in size and function (see apical four chamber [Video 3] and subcostal view [Video 4]) (choice C is incorrect). This would not be the case with a large, hemodynamically significant pulmonary embolism (see example in Video 5).

This is unlikely to indicate acute myocardial infarction because there is global left ventricular dysfunction rather than segmental defects, and the ECG is normal. The patient also reports no acute chest pain (choice D is incorrect). Videos 6 to 9 are from the patient's point-of-care ultrasonographic examination for comparison.