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Cytokine storm and histopathological findings in 60 cases of COVID-19-related death: from viral load research to immunohistochemical quantification of major players IL-1β, IL-6, IL-15 and TNF-α
Forensic Science, Medicine and Pathology ( IF 1.5 ) Pub Date : 2021-08-31 , DOI: 10.1007/s12024-021-00414-9
Paolo Frisoni 1 , Margherita Neri 1 , Letizia Alfieri 1 , Stefano D’Errico 2 , Martina Zanon 2 , Diana Bonuccelli 3 , Massimo Martelloni 3 , Mariano Cingolani 4 , Roberto Scendoni 4 , Marco Di Paolo 5 , Rosa Maria Gaudio 6 , Matteo Marti 6 , Maurizio Lestani 7 , Carlo Moreschi 8 , Alessandro Santurro 9 , Matteo Scopetti 9 , Paola Frati 9 , Vittorio Fineschi 9 , Ombretta Turriziani 10
Affiliation  

This study involves the histological analysis of samples taken during autopsies in cases of COVID-19 related death to evaluate the inflammatory cytokine response and the tissue localization of the virus in various organs. In all the selected cases, SARS-CoV-2 RT-PCR on swabs collected from the upper (nasopharynx and oropharynx) and/or the lower respiratory (trachea and primary bronchi) tracts were positive. Tissue localization of SARS-CoV-2 was detected using antibodies against the nucleoprotein and the spike protein. Overall, we tested the hypothesis that the overexpression of proinflammatory cytokines plays an important role in the development of COVID-19-associated pneumonia by estimating the expression of multiple cytokines (IL-1β, IL-6, IL-10, IL-15, TNF-α, and MCP-1), inflammatory cells (CD4, CD8, CD20, and CD45), and fibrinogen. Immunohistochemical staining showed that endothelial cells expressed IL-1β in lung samples obtained from the COVID-19 group (p < 0.001). Similarly, alveolar capillary endothelial cells showed strong and diffuse immunoreactivity for IL-6 and IL-15 in the COVID-19 group (p < 0.001). TNF-α showed a higher immunoreactivity in the COVID-19 group than in the control group (p < 0.001). CD8 + T cells where more numerous in the lung samples obtained from the COVID-19 group (p < 0.001). Current evidence suggests that a cytokine storm is the major cause of acute respiratory distress syndrome (ARDS) and multiple organ failure and is consistently linked with fatal outcomes.



中文翻译:

60 例 COVID-19 相关死亡病例的细胞因子风暴和组织病理学发现:从病毒载量研究到主要参与者 IL-1β、IL-6、IL-15 和 TNF-α 的免疫组织化学定量

本研究涉及对 COVID-19 相关死亡病例尸体解剖期间采集的样本进行组织学分析,以评估炎性细胞因子反应和病毒在各个器官中的组织定位。在所有选定的病例中,从上呼吸道(鼻咽和口咽)和/或下呼吸道(气管和原发性支气管)采集的拭子上的 SARS-CoV-2 RT-PCR 呈阳性。使用针对核蛋白和刺突蛋白的抗体检测了 SARS-CoV-2 的组织定位。总体而言,我们通过估计多种细胞因子(IL-1β、IL-6、IL-10、IL-15、 TNF-α 和 MCP-1)、炎症细胞(CD4、CD8、CD20 和 CD45)和纤维蛋白原。免疫组织化学染色显示内皮细胞在从 COVID-19 组获得的肺样本中表达 IL-1β(p < 0.001)。同样,在 COVID-19 组中,肺泡毛细血管内皮细胞对 IL-6 和 IL-15 表现出强烈且弥散的免疫反应性(p < 0.001)。TNF-α 在 COVID-19 组中显示出比对照组更高的免疫反应性(p < 0.001)。CD8 + T 细胞在从 COVID-19 组获得的肺样本中更多(p < 0.001)。目前的证据表明,细胞因子风暴是急性呼吸窘迫综合征 (ARDS) 和多器官衰竭的主要原因,并且始终与致命结果相关。在 COVID-19 组中,肺泡毛细血管内皮细胞对 IL-6 和 IL-15 表现出强烈且弥漫的免疫反应性(p < 0.001)。TNF-α 在 COVID-19 组中显示出比对照组更高的免疫反应性(p < 0.001)。CD8 + T 细胞在从 COVID-19 组获得的肺样本中更多(p < 0.001)。目前的证据表明,细胞因子风暴是急性呼吸窘迫综合征 (ARDS) 和多器官衰竭的主要原因,并且始终与致命结果相关。在 COVID-19 组中,肺泡毛细血管内皮细胞对 IL-6 和 IL-15 表现出强烈且弥漫的免疫反应性(p < 0.001)。TNF-α 在 COVID-19 组中显示出比对照组更高的免疫反应性(p < 0.001)。CD8 + T 细胞在从 COVID-19 组获得的肺样本中更多(p < 0.001)。目前的证据表明,细胞因子风暴是急性呼吸窘迫综合征 (ARDS) 和多器官衰竭的主要原因,并且始终与致命结果相关。

更新日期:2021-09-01
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