key: cord-0847344-xpua2e0a authors: Yamada, Yasuhiro; Fujinami, Kaoru; Eguchi, Tadashi; Takefuji, Hiroshi; Mori, Nobuaki title: Multisystem Inflammatory Syndrome in Adults after Mild SARS-CoV-2 Infection, Japan date: 2021-06-03 journal: Emerg Infect Dis DOI: 10.3201/eid2706.210728 sha: cfd295d205c6f8d0c450ead8c2ef32b18409bcb8 doc_id: 847344 cord_uid: xpua2e0a In Japan, a 51-year-old man had minimally symptomatic severe acute respiratory syndrome coronavirus 2 infection. Multisystem inflammatory syndrome was diagnosed ≈5 weeks later; characteristics included severe inflammation, cardiac dysfunction, and IgG positivity. Clinicians should obtain detailed history and examine IgG levels for cases of inflammatory disease with unexplained cardiac decompensation. Yasuhiro Yamada, 1 In Japan, a 51-year-old man had minimally symptomatic severe acute respiratory syndrome coronavirus 2 infection. Multisystem inflammatory syndrome was diagnosed ≈5 weeks later; characteristics included severe inflammation, cardiac dysfunction, and IgG positivity. Clinicians should obtain detailed history and examine IgG levels for cases of inflammatory disease with unexplained cardiac decompensation. O ver the course of the coronavirus disease pandemic, severe inflammatory syndromes have been reported in children (1) (2) (3) . Since June 2020, the same syndrome has also been reported in adults. The Centers for Disease Control and Prevention has been collecting case reports of multisystem inflammatory syndrome in adults (MIS-A) and published a case series of MIS-A reported from the United Kingdom and United States in November 2020 (4) . A healthy 51-year-old man in Japan tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by PCR on a saliva sample after his wife was infected with SARS-CoV-2. The positive result was obtained 37 days before hospital admission. During the course of his SARS-CoV-2 infection, his only symptom was olfactory disturbance; he had no respiratory symptoms or fever. He became aware of swelling in the right side of his neck and fatigue 3 days before admission. He visited an internal medicine clinic 2 days before admission for sore throat and fever in the range of 38°C and was prescribed levofloxacin for pharyngitis. He initially came to the emergency department of National Hospital Organization Tokyo Medical Center because of fever and sore throat, which did not improve. On examination, we noted enlargement of the right cervical lymph nodes, and cervical contrast-enhanced computed tomography revealed lymph nodes swollen to 20 mm localized in the right side of the neck and swelling of the posterior wall of the middle pharynx. The patient was admitted with a diagnosis of lymphadenitis, and we initiated ampicillin/sulbactam. The patient became acutely hypotensive with blood pressure of 73/45 mm Hg 2 days after admission. He was treated with noradrenaline and dobutamine, but blood pressure did not increase despite crystalloid fluid infusion. We changed antibiotics to meropenem and vancomycin, and 100 mg hydrocortisone was administered empirically to treat septic shock. An electrocardiogram showed a negative T wave and sinus tachycardia. Echocardiography showed ejection fraction of 42% and overall decreased left ventricular contraction. No pericardial effusion was observed. Systemic computed tomography showed enlarged lymph nodes only in the right side of the neck and no pneumonia in the lung fields. The patient was admitted to the intensive care unit (ICU) (Table) . The patient's circulation stabilized, and the swollen cervical lymph nodes improved a few days after ICU admission. During his stay in the ICU, we observed generalized edema. However, as inflammation improved, his urine volume increased, and the edema improved. We observed conjunctivitis 8 days after admission. No skin rash or desquamation was observed. Echocardiography performed 11 days after admission showed improvement in cardiac contraction to 64%, and the duration of fever >38°C was 8 days. Cultures of blood collected at admission yielded negative results. Coronary computed tomography angiography showed no aneurysms or other abnormalities in the coronary arteries. The case definition of MIS-A in the Centers for Disease Control and Prevention report (4) lists the following 5 criteria: 1) severe illness requiring hospitalization in a person >21 years of age; 2) a positive test result for current or previous SARS-CoV-2 infection (nucleic acid, antigen, or antibody) during admission or in the previous 12 weeks; 3) severe dysfunction of >1 extrapulmonary organ systems (e.g., hypotension or shock, cardiac dysfunction, arterial or venous thrombosis or thromboembolism, or acute liver injury); 4) laboratory evidence of severe inflammation (e.g., elevated C-reactive protein, ferritin, D-dimer, or interleukin-6); and 5) absence of severe respiratory illness (to exclude patients in which inflammation and organ dysfunction might be attributable simply to tissue hypoxia). This case meets all of these criteria. Whether MIS-A is associated with acute SARS-CoV-2 infection or is a reaction after acute infection is unclear. In this case, the case-patient's positive SARS-CoV-2 test result occurred 37 days before the onset of MIS-A, and IgG levels were already elevated at the time of admission. This fact supports the notion that MIS-A can occur after the acute phase of SARS-CoV-2 infection. The only symptom at the time of infection was olfactory disturbance, which is similar to other case reports of MIS-A occurring in asymptomatic or minimally symptomatic patients (5) . It has been reported that MIS-A can cause symptoms similar to those of Kawasaki disease (6) . This case did not meet the American College of Cardiology criteria for Kawasaki disease (7) but did meet the definition of incomplete Kawasaki disease. Conjunctivitis persisted for 4 weeks after the onset of MIS-A and gradually improved. In February 2021, a case definition was proposed for reporting cases of multisystem inflammatory syndrome in adults and children after vaccination (8) . Considering the possibility that the disease develops after asymptomatic SARS-CoV-2 infection and that increased IgG levels can be involved, MIS-A is rare, but the disease concept of MIS-A should be widely acknowledged. Clinicians should consider obtaining detailed history and examining SARS-CoV-2 IgG levels for cases of severe inflammatory disease with unexplained cardiac decompensation. Pan American Health Organization/World Health Organization. Interim guidelines for detecting cases of reinfection by SARS-CoV-2 Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR Comparison of the GeneFinder COVID-19 Plus RealAmp Kit on the sampleto-result Platform ELITe InGenius to the national reference method: an added value of N gene target detection? Confirmed reinfection with SARS-CoV-2 variant VOC-202012/01 Genomic evidence of SARS-CoV-2 reinfection involving E484K spike mutation A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology Brazil-UK Centre for Arbovirus Discovery, Diagnosis, Genomics and Epidemiology Genomic Network. Evolution and epidemic spread of SARS-CoV-2 in Brazil Spike mutation D614G alters SARS-CoV-2 fitness Evidence of SARS-CoV-2 reinfection without mutations in spike protein California MIS-C Response Team. COVID-19-associated multisystem inflammatory syndrome in children-United States SARS-CoV-2-related paediatric inflammatory multisystem syndrome, an epidemiological study Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 Case series of multisystem inflammatory syndrome in adults associated with SARS-CoV-2 infection-United Kingdom and United States Coronavirus disease 2019 acute myocarditis and multisystem inflammatory syndrome in adult intensive and cardiac care units An adult with Kawasaki-like multisystem inflammatory syndrome associated with COVID-19 American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young Council on Cardiovascular Surgery and Anesthesia; and Council on Epidemiology and Prevention. Diagnosis, treatment, and long-term management of Kawasaki disease: a scientific statement for health professionals from the American Heart Association Multisystem inflammatory syndrome in children and adults (MIS-C/A): case definition & guidelines for data collection, analysis, and presentation of immunization safety data We thank Shinichi Kimura and Yurie Yamazaki for intensive care, and we thank the clinical staff at National Hospital Organization Tokyo Medical Center for their dedicated clinical practice and patient care. Dr. Yasuhiro Yamada is a physician at National Hospital Organization Tokyo Medical Center, Tokyo, Japan. His research interests include general internal medicine and health economics.