Data_Sheet_1_Neutrophil infiltration and myocarditis in patients with severe COVID-19: A post-mortem study.docx

AimsTo investigate cardiac pathology in critically ill patients with coronavirus disease 2019 (COVID-19) and identify associations between pathological changes and clinical characteristics.
MethodsThe present autopsy cohort study included hearts from 26 deceased patients hospitalized in intensive care units due to COVID-19, and was conducted at four sites in Wuhan, China. Cases were divided into a neutrophil infiltration group and a no-neutrophil group based on the presence or absence of histopathologically identified neutrophilic infiltrates.
ResultsAmong the 26 patients, histopathological examination identified active myocarditis in four patients. All patients with myocarditis exhibited extensive accompanying neutrophil infiltration, and all patients without myocarditis did not. The neutrophil infiltration group exhibited significantly higher rates of detection of interleukin-6 (100 vs. 4.6%) and tumor necrosis factor-alpha (100 vs. 31.8%) than the no-neutrophil group (both p < 0.05). On admission, four patients with neutrophil infiltration in myocardium had significantly higher baseline levels of aspartate aminotransferase, D dimer, and high-sensitivity C reactive protein than the other 22 patients (all p < 0.05). During hospitalization, patients with neutrophil infiltration had significantly higher maximum creatine kinase-MB (median 280.0 IU/L vs. 38.7 IU/L, p = 0.04) and higher troponin I (median 1.112 ng/ml vs. 0.220 ng/ml, p = 0.56) than patients without neutrophil infiltration.
ConclusionActive myocarditis was frequently associated with neutrophil infiltration in the hearts of deceased patients with severe COVID-19. Patients with neutrophil-infiltrated myocarditis had a series of severely abnormal laboratory test results on admission, and high maximum creatine kinase-MB during hospitalization. The role of neutrophils in severe heart injury and systemic conditions in patients with COVID-19 should be emphasized.

目的 本研究旨在探讨新型冠状病毒肺炎（coronavirus disease 2019, COVID-19）重症患者的心脏病理学特征，并明确病理改变与临床特征之间的关联。
方法 本尸检队列研究纳入了26例因COVID-19入住重症监护病房的死亡患者的心脏标本，研究在中国武汉的4个研究中心开展。研究人员依据组织病理学检测是否检出中性粒细胞浸润，将所有病例划分为中性粒细胞浸润组与无中性粒细胞浸润组。
结果 26例患者中，组织病理学检查检出4例活动性心肌炎。所有合并心肌炎的患者均伴随广泛的中性粒细胞浸润，而无心肌炎患者均未出现该表现。与无中性粒细胞浸润组相比，中性粒细胞浸润组的白细胞介素-6（interleukin-6, IL-6）与肿瘤坏死因子-α（tumor necrosis factor-alpha, TNF-α）检出率均显著更高（100% vs. 4.6%、100% vs. 31.8%，均p < 0.05）。入院时，心肌存在中性粒细胞浸润的4例患者的天冬氨酸氨基转移酶、D-二聚体及高敏C反应蛋白基线水平均显著高于其余22例患者（均p < 0.05）。住院期间，中性粒细胞浸润组患者的肌酸激酶同工酶-MB（creatine kinase-MB, CK-MB）峰值水平显著更高[中位数280.0 IU/L vs. 38.7 IU/L，p = 0.04]，而肌钙蛋白I水平亦更高[中位数1.112 ng/ml vs. 0.220 ng/ml，p = 0.56]。
结论 重症新型冠状病毒肺炎死亡患者的心脏中，活动性心肌炎常与中性粒细胞浸润相关。伴随中性粒细胞浸润的心肌炎患者在入院时即出现多项严重异常的实验室检测结果，且住院期间肌酸激酶同工酶-MB峰值水平较高。本研究强调了中性粒细胞在新型冠状病毒肺炎患者重症心脏损伤及全身病理生理过程中的作用。