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Multisystem Inflammatory Syndrome in Adults after Mild SARS-CoV-2 Infection, Japan.

Over the course of the coronavirus disease pandemic, severe inflammatory syndromes have been reported in children (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[degrees]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[degrees]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 [subsection][greater than or equal to] 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.



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.


(1.) Godfred-Cato S, Bryant B, Leung J, Oster ME, Conklin L, Abrams J, et al.; California MIS-C Response Team. COVID-19-associated multisystem inflammatory syndrome in children-United States, March-July 2020. MMWR Morb Mortal Wkly Rep. 2020;69:1074-80. 10.15585/mmwr.mm6932e2

(2.) Belot A, Antona D, Renolleau S, Javouhey E, Hentgen V, Angoulvant F, et al. SARS-CoV-2-related paediatric inflammatory multisystem syndrome, an epidemiological study, France, 1 March to 17 May 2020. Euro Surveill. 2020;25:2001010. ES.2020.25.22.2001010

(3.) Whittaker E, Bamford A, Kenny J, Kaforou M, Jones CE, Shah P, et al.; PIMS-TS Study Group and EUCLIDS and PERFORM Consortia. Clinical characteristics of 58 children with a pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2. JAMA. 2020;324:259-69.

(4.) Morris SB, Schwartz NG, Patel P, Abbo L, Beauchamps L, Balan S, et al. Case series of multisystem inflammatory syndrome in adults associated with SARS-CoV-2 infection--United Kingdom and United States, March-August 2020. MMWR Morb Mortal Wkly Rep. 2020;69:1450-6.

(5.) Hekimian G, Kerneis M, Zeitouni M, Cohen-Aubart F, Chommeloux J, Brechot N, et al. Coronavirus disease 2019 acute myocarditis and multisystem inflammatory syndrome in adult intensive and cardiac care units. Chest. 2021; 159:657-62.

(6.) Shaigany S, Gnirke M, Guttmann A, Chong H, Meehan S, Raabe V, et al. An adult with Kawasaki-like multisystem inflammatory syndrome associated with COVID-19. Lancet. 2020;396:e8-10.

(7.) McCrindle BW, Rowley AH, Newburger JW, Burns JC, Bolger AF, Gewitz M, et al.; American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; 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. Circulation. 2017;135:e927-99.

(8.) Vogel TP, Top KA, Karatzios C, Hilmers DC, Tapia LI, Moceri P, et al. Multisystem inflammatory syndrome in children and adults (MIS-C/A): case definition & guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine. 2021 Feb 25 [Epub ahead of print].

Yasuhiro Yamada, [1] Kaoru Fujinami, [1] Tadashi Eguchi, Hiroshi Takefuji, Nobuaki Mori

[1] These first authors contributed equally to this article.

Address for correspondence: Yasuhiro Yamada, Department of General Internal Medicine, National Hospital Organization Tokyo Medical Center, Tokyo, 152-8902, Japan; email:

Author affiliations: National Hospital Organization Tokyo Medical Center, Tokyo, Japan (Y. Yamada, K. Fujinami, T. Eguchi, H. Takefuji, N. Mori); University College London, London, UK (K. Fujinami)
Table. Laboratory studies performed at intensive care unit
admission of patient with multisystem inflammatory syndrome
after mild severe acute respiratory syndrome coronavirus 2
infection, Japan

Laboratory test              Result       range

C-reactive protein, mg/dL     36.77       <0.14
Procalcitonin, ng/mL          3.67        <0.05
Interleukin 6, pg/dL           565         <4
Leukocyte count,              22.4       3.0-8.6
* [10.sup.9] cells/L
Neutrophil count,             21.0       1.5-5.8
* [10.sup.9] cells/L
Lymphocyte count,              1.0       1.0-3.0
* [10.sup.9] cells/L
Hemoglobin, g/dL              13.2      13.7-16.8
Platelets, * [10.sup.9]/L      180       158-348
Serum creatinine, mg/dL       2.54      0.65-1.07
Albumin, g/dL                  2.5       4.1-5.1
Aspartate                      19         13-30
aminotransferase, U/L
Alanine                        37         10-42
aminotransferase, U/L
Ferritin, ng/mL               1563      17.9-464
Fibrinogen, mg/dL             >900       200-400
D-dimer, ng/mL                 5.7         <1
Creatine                       37        59-248
phosphokinase, U/L
Troponin T, ng/mL             0.861      <0.014
B-type natriuretic            >2000       <18.4
peptide, pg/mL
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Article Details
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Author:Yamada, Yasuhiro; Fujinami, Kaoru; Eguchi, Tadashi; Takefuji, Hiroshi; Mori, Nobuaki
Publication:Emerging Infectious Diseases
Article Type:Clinical report
Geographic Code:9JAPA
Date:Jun 1, 2021
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