Multisystem Inflammatory Syndrome after SARS-CoV-2 Infection and COVID-19 Vaccination

We report 3 patients in California, USA, who experienced multisystem inflammatory syndrome (MIS) after immunization and severe acute respiratory syndrome coronavirus 2 infection. During the same period, 3 adults who were not vaccinated had MIS develop at a time when ≈7% of the adult patient population had received >1 vaccine.


The Study
Patient 1 was a 20-year-old Hispanic woman who sought care for 3 days of a diffuse body rash, tac-tile fever, sore throat, mild neck discomfort, and fatigue. There was no cough, congestion, headache, or abdominal pain. She had vomiting and diarrhea, which had subsided 8 days before admission. She received her fi rst dose of SARS-CoV-2 vaccine 15 days before admission. She had no known coronavirus disease (COVID-19) exposure but was SARS-CoV-2 PCR and nucleocapsid IgG positive. She was hypotensive at arrival to the emergency department, requiring inotropic support. She had elevated troponin and brain natriuretic peptide (BNP) with a left ventricular ejection fraction initially mildly reduced at 45% but 30%-35% the following day. She responded well to therapy with intravenous immunoglobulin (IVIG) and methylprednisolone (Table 1).
Patient 2 was a 40-year-old Hispanic man who sought care after 6 days of episodic fevers up to 101.7°F. Associated symptoms included dyspnea on exertion, headache, neck pain, lethargy, abdominal pain, and diarrhea. No chest pain was present. He had a history of SARS-CoV-2 vaccination and laboratory-confi rmed mild to moderate COVID-19, both within 48 days before seeking care (Figure). His exam was notable for sweats, diffuse abdominal pain on palpation, tachycardia, and tachypnea. Patient 2 fulfi lled Brighton Level 1 criteria for MIS-A with documented fevers, gastrointestinal and neurologic symptoms, elevated infl ammatory and cardiac markers, and electrocardiogram changes that were concerning for myocarditis (3). He responded well to treatment with dexamethasone (Table 1).
Patient 3 was an 18-year-old Asian American man who sought care at the emergency department with a history of 3 days of fever as high as 104°F with headache, vomiting, diarrhea, and abdominal cramping (Figure). He denied any upper respiratory symptoms. He had a history of a laboratoryconfi rmed COVID-19 infection 6 weeks before the onset of symptoms and received the fi rst dose of the SARS-CoV-2 vaccine 18 days before the onset of symptoms. In the emergency department, he was found to be hyponatremic and hypotensive (Table  1). His examination was notable for tachycardia and abdominal tenderness. He had elevated inflammatory markers, thrombocytopenia, and lymphopenia. Echocardiogram revealed mild to moderate reduced systolic function with an ejection fraction of 40%-45%. He responded well to therapy with methylprednisolone, IVIG, and anakinra. Patient 4 was a 62-year-old Asian American man who sought care at the emergency department for fever lasting 5 days. For 6 days he had had nausea and vomiting, which developed 23 days after a laboratory-confirmed mild to moderate acute COVID-19 illness that subsided after 1 week. He also had 4 days of bilateral hearing loss. He was hypotensive, requiring inotropic support. He had thrombocytopenia, elevated inflammatory markers, and elevated troponin with diffuse ST elevations on electrocardiogram (Table 2). He responded well to treatment with methylprednisolone, including improvement in his hearing loss.

Multisystem Infl ammatory Syndrome after SARS-CoV-2 Infection and COVID-19 Vaccination
Patient 5 was a 29-year-old Hispanic woman who experienced fever, chills, headache, and nausea 28 days after a laboratory-confirmed acute COVID-19 illness. She sought care at the emergency department with hypotension requiring inotropic support. Clinicians diagnosed MIS-A on the basis of conjunctivitis, evidence of colitis on abdominal imaging, elevated inflammatory markers, lymphopenia, and elevated BNP. She responded well to treatment with methylprednisolone and IVIG (Table 2). Patient 6 was a 23-year old Hispanic man who experienced fever and abdominal pain 38 days after a laboratory-confirmed mild to moderate acute CO-VID-19 illness. He was hypotensive, requiring inotropic support. He had mesenteric adenitis on abdominal imaging. He had elevated inflammatory markers, neutrophilia, lymphopenia, and a left ventricular ejection fracture of 20% on echocardiogram. He was treated with IVIG and methylprednisolone ( Table 2). He died 12 days after admission.

Conclusions
At the time of our study, our medical group was only vaccinating healthcare workers and patients >75 years of age. The 3 patients that were immunized qualified for early vaccination because they either worked or volunteered in a healthcare setting. These cases occurred ≈1 month after the peak surge of COVID-19 cases in Southern California. At the time these patients sought care, only ≈7% of the adult (>18 years of age) population who were 1946 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 27, No. 7, July 2021  members of the Kaiser Permanente patient group (≈3,776,000 members) had received >1 SARS-CoV-2 vaccine, whereas 3 of the 6 patients in this study who had MIS were vaccinated. These 6 patients were hospitalized at 5 of the 15 Kaiser Permanente medical centers across Southern California. We believe the temporal association after SARS-CoV-2 immunization is worth noting, given the theoretical concern of MIS-C/A after vaccination (3). We did not identify any patients with MIS after vaccination who did not have recent SARS-CoV-2 infection. It is possible that other case-patients in our member population were hospitalized outside of our 15 medical centers and thus were not captured for this case series. Overall, MIS is rare in adults. In comparison we treated >50 children with MIS-C during January 2021-February 2021 and >100 since May 2020 among a pediatric population of 960,000.
The Centers for Disease Control and Prevention (CDC) allows for vaccination after a SARS-CoV-2 infection after recovery from the acute illness and after the isolation period, with no recommended minimal interval between infection and vaccination (4). Most cases of MIS-C/A occur 2-6 weeks after an exposure or infection (1-3), although we have seen several children brought for care as late as 8-10 weeks after a confirmed infection or exposure. We need to continue to monitor for MIS-C/A after SARS-CoV-2 infection and immunization as more of the population are vaccinated, especially as vaccines are administered to children who are at higher risk for MIS. CDC and the US Food and Drug Administration co-manage VAERS (the Vaccine Adverse Event Reporting System), which is being used to monitor for adverse events after COVID-19 vaccines. MIS-C/A is listed as a postvaccination adverse event of special interest (5) and should be reported to VAERS (6).