Multisystem Inflammatory Syndrome in Adults After Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection and Coronavirus Disease 2019 (COVID-19) Vaccination

Abstract

Background Multisystem inflammatory syndrome in adults (MIS-A) was reported in association with the COVID-19 pandemic. MIS-A was included in the list of adverse events to be monitored as part of the emergency use authorizations issued for COVID-19 vaccines. Methods Reports of MIS-A patients received by the Centers for Disease Control and Prevention (CDC) after COVID-19 vaccines became available were assessed. Data collected on the patients included clinical and demographic characteristics and their vaccine status. The Vaccine Adverse Events Reporting System (VAERS) was also reviewed for possible cases of MIS-A. Results From December 14, 2020 to April 30, 2021, 20 patients who met the case definition for MIS-A were reported to CDC. Their median age was 35 years (range, 21-66 years), and 13 (65%) were male. Overall, 16 (80%) patients had a preceding COVID-19-like illness a median of 26 days (range 11-78 days) before MIS-A onset. All 20 patients had laboratory evidence of SARS-CoV-2 infection. Seven MIS-A patients (35%) received COVID-19 vaccine a median of 10 days (range, 6-45 days) before MIS-A onset; 3 patients received a second dose of COVID-19 vaccine 4, 17, and 22 days before MIS-A onset. Patients with MIS-A predominantly had gastrointestinal and cardiac manifestations and hypotension or shock. Conclusions Although 7 patients were reported to have received COVID-19 vaccine, all had evidence of prior SARS-CoV-2 infection. Given the widespread use of COVID-19 vaccines, the lack of reporting of MIS-A associated with vaccination alone, without evidence of underlying SARS-CoV-2 infection, is reassuring.

Reported cases of multisystem inflammatory syndrome in children aged 12–20 years in the USA who received a COVID-19 vaccine, December, 2020, through August, 2021: a surveillance investigation

“…Multisystem inflammatory syndrome in adults was not reported in clinical trials of COVID-19 vaccines used in the USA, and MIS-C was not observed in the 46 000 individuals aged 16 years or older who participated in safety clinical trials for BNT162b2. 10 , 25 Globally, MIS-C in individuals who had received a COVID-19 vaccine has been described in detail in the literature for eight individuals younger than 21 years, 22 , 26 , 27 , 28 , 29 , 30 , 31 excluding aggregate counts from larger analyses assessing the effect of vaccination on preventing MIS-C. 32 , 33 From the USA, two reports included three cases that are also in our surveillance results, 22 , 26 and one report described a 14-year-old child with evidence of previous SARS-CoV-2 infection (positive anti-nucleocapsid antibody test) with MIS-C onset 2 months after a second dose with BNT162b2. 31 From outside the USA, we found reports of two individuals without evidence of previous or recent SARS-CoV-2 infection and who tested negative for anti-nucleocapsid antibodies: from Denmark, a 17-year-old with MIS-C onset 5 days after dose two of BNT162b2; 28 and from Turkey, a 12-year-old with onset 27 days after dose one of BNT162b2.…”

Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) Aged 12–20 Years in the United States Who Received COVID-19 Vaccine, December 2020 through August 2021

“…29 Several adults have also been reported with MIS-A following COVID-19 vaccination, most of whom had evidence of previous SARS-CoV-2 infection. 23,26 This investigation highlights the challenges of diagnosing MIS-C and importance of a thorough clinical evaluation. While the CDC MIS-C case definition can be met with any type of SARS-CoV-2 antibody test (anti-spike, anti-nucleocapsid, or undifferentiated), testing for anti-nucleocapsid antibody in persons with suspected MIS-C after COVID-19 vaccination may differentiate between vaccine-versus infection-derived antibody.…”

“…Neither MIS-C nor multisystem inflammatory syndrome in adults (MIS-A) was reported in the clinical trials of COVID-19 vaccines used in the United States. 14,26 Globally, MIS-C following COVID-19 vaccination has been reported in the literature for six persons <21 years of age. 23,[27][28][29][30] Two of these persons are from the United States and are included in our case series; both had evidence of SARS-CoV-2 infection.…”

Case Report: MIS-C With Prominent Hepatic and Pancreatic Involvement in a Vaccinated Adolescent – A Critical Reasoning

“…Moreover, although MIS-C seems a post-infectious severe event arising from a dysregulated immune response leading to a hyperinflammatory state, its pathogenesis is not completely elucidated. Different theories have been formulated to explain its outbreak during the pandemic, including the role of molecular mimicry, superantigen-dependent immune activation, delayed interferon response, presence of anti-interferon autoantibodies, dysregulation of the inflammasome by an extensive innate immune response primed by Toll-like Receptors expressed on ACE + type II pneumocytes, antibody-dependent enhancement, and others ( 11 – 13 ). Specific molecular signatures have been evidenced in MIS-C patients, highlighting the role of type II interferon and NF-κB activation in its pathogenesis ( 14 ).…”

“…To our knowledge, only rare cases of multisystem inflammatory syndrome directly triggered by SARS-CoV-2 vaccination have been reported in adults and adolescents ( 13 , 17 – 19 ). Also the reports of classical case of MIS-C (triggered by SARS-CoV-2 exposure) in vaccinated patients are of extreme rarity.…”