An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study

意大利SARS-CoV-2流行病的疫情中心爆發重度川崎病樣疾病：一項觀察性隊列研究

Summary

摘要

Background The Ber province, which is extensively affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic, is a natural observatory of virus manifestations in the general population. In the past month we recorded an outbreak of Kawasaki disease; we aimed to evaluate incidence and features of patients with Kawasaki-like disease diagnosed during the SARS-CoV-2 epidemic.

背景 受重度急性呼吸道綜合征冠狀病毒2（SARS-CoV-2）疫情廣泛影響的貝加莫省是普通人群中病毒表現的天然觀察站。在過去的一個月里，我們記錄到川崎病暴發；我們旨在評估川崎病樣疾病的發病率以及SARS-CoV-2疫情期間確診為川崎病樣疾病的患者的特征。

Methods All patients diagnosed with a Kawasaki-like disease at our centre in the past 5 years were divided according to symptomatic presentation before (group 1) or after (group 2) the beginning of the SARS-CoV-2 epidemic. Kawasaki-like presentations were managed as Kawasaki disease according to the American Heart Association indications. Kawasaki disease shock syndrome (KDSS) was defined by presence of circulatory dysfunction, and macrophage activation syndrome (MAS) by the Paediatric Rheumatology International Trials Organisation criteria. Current or previous infection was sought by reverse-transcriptase quantitative PCR in nasopharyngeal and oropharyngeal swabs, and by serological qualitative test detecting SARS-CoV-2 IgM and IgG, respectively.

方法 過去5年中在我們中心確診為川崎病樣疾病的所有患者，按照癥狀出現于SARS-CoV-2疫情開始前（第1組）或開始后（第2組）分組。根據美國心臟協會的指示，川崎病樣疾病表征按照川崎病實施管理。川崎病休克綜合征（Kawasaki disease shock syndrome，KDSS）定義為，依據國際兒童風濕病試驗組織的標準，存在循環功能障礙和巨噬細胞活化綜合征（MAS）。通過對鼻咽和口咽拭子樣本實施逆轉錄酶定量PCR和血清學定性測試分別檢測SARS-CoV-2 IgM和IgG，以確定當前或既往感染情況。

Findings Group 1 comprised 19 patients (seven boys, 12 girls; aged 3·0 years [SD 2·5]) diagnosed between Jan 1, 2015, and Feb 17, 2020. Group 2 included ten patients (seven boys, three girls; aged 7·5 years [SD 3·5]) diagnosed between Feb 18 and April 20, 2020; eight of ten were positive for IgG or IgM, or both. The two groups differed in disease incidence (group 1 vs group 2, 0·3 vs ten per month), mean age (3·0 vs 7·5 years), cardiac involvement (two of 19 vs six of ten), KDSS (zero of 19 vs five of ten), MAS (zero of 19 vs five of ten), and need for adjunctive steroid treatment (three of 19 vs eight of ten; all p<0·01).

結果 組1包括19名患者（7名男孩，12名女孩；年齡3-0歲[SD 2-5]），診斷時間為2015年1月1日至2020年2月17日。組2包括10名患者（7名男孩，3名女孩；年齡7-5歲[SD 3-5]），診斷時間為2020年2月18日-4月20日；10名患者中8名為IgG或IgM陽性，或兩者均為陽性。兩組在疾病發生率（組1 vs組2，每月0-3次vs 每月10次）、平均年齡（3-0歲vs 7-5歲）、心臟受累（19名患者中2例 vs 10名患者中6例）、KDSS（19例患者中0例 vs 10名患者中5例）、MAS（19例患者中0例vs 10名患者中5例）、需要輔助類固醇治療（19例患者中3例 vs 10名患者中8例；均為P<0-01）等方面存在差異。

Interpretation In the past month we found a 30-fold increased incidence of Kawasaki-like disease. Children diagnosed after the SARS-CoV-2 epidemic began showed evidence of immune response to the virus, were older, had a higher rate of cardiac involvement, and features of MAS. The SARS-CoV-2 epidemic was associated with high incidence of a severe form of Kawasaki disease. A similar outbreak of Kawasaki-like disease is expected in countries involved in the SARS-CoV-2 epidemic.

解釋 在過去的一個月里，我們發現川崎病樣疾病的發病率升高了30倍。SARS-CoV-2疫情開始后確診的兒童中表現出針對病毒的免疫反應的證據，年齡較大，心臟受累率更高，且具有MAS的特征。SARS-CoV-2疫情與重度川崎病樣疾病的發病率較高相關。預計SARS-CoV-2疫情涉及的國家也會出現類似的川崎病樣疾病爆發。

圖. 研究期間和過去5年川崎病發病率 （A）過去5年川崎病發病率（B）疫情期間川崎病發病率