Broncho-alveolar inflammation in COVID-19 patients: a correlation with clinical outcome.

Broncho-alveolar inflammation in COVID-19 patients: a correlation with clinical outcome.
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DOI:
10.1186/s12890-020-01343-z
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发表时间:
2020-11-16
影响因子:
3.1
通讯作者:
Meloni F
Meloni F
中科院分区:
医学3区
文献类型:
--
作者:
Pandolfi L;Fossali T;Frangipane V;Bozzini S;Morosini M;D'Amato M;Lettieri S;Urtis M;Di Toro A;Saracino L;Percivalle E;Tomaselli S;Cavagna L;Cova E;Mojoli F;Bergomi P;Ottolina D;Lilleri D;Corsico AG;Arbustini E;Colombo R;Meloni F

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严重急性呼吸综合征冠状病毒2(SARS-CoV-2)迅速达到大流行的程度。鉴于SARS-CoV-2的主要靶点是肺部,导致严重肺炎,并伴有炎症级联反应的过度激活,我们进行了一项前瞻性研究,以评估中度至重度COVID-19患者的肺泡炎症状态。通过实时PCR对入住重症监护室(ICU)(n = 28)和中级医学病房(IMW)(n = 5)的33例SARS-CoV-2感染的成人患者的鼻咽拭子进行诊断性支气管肺泡灌洗(BAL)。检测细胞分类计数、细胞超微结构及白细胞介素6、8、10水平。重症监护室患者的中性粒细胞明显增加(1.24 × 105 ml− 1,0.85-2.07),低淋巴细胞(0.97 × 105 ml-1,0.024-0.34)和巨噬细胞部分(0.43 × 105 ml− 1,0.34-1.62)与IMW患者相比(分别为0.095 × 105 ml-1,0.05-0.73; 0.47 × 105 ml-1,0.28-1.01和2.14 × 105 ml-1,1.17-3.01)(p < 0.01)。通过电子透射显微镜对ICU患者BAL的研究显示,通过抗病毒衣壳和刺突抗体的免疫染色证实了单核细胞内的病毒颗粒。ICU患者中的IL 6和IL 8显著高于IMW(IL 6 p < 0.01,IL 8 p < 0.0001),并且在未存活的患者中也显著高于IMW(IL 6 p < 0.05,IL 8 p = 0.05 vs.存活者)。IL 10在组间未显示显著变化。按接受的治疗对患者进行分类,发现与托珠单抗(p < 0.1)或抗病毒药(p < 0.05)治疗的患者相比,用类固醇治疗的患者中IL 6的BAL浓度较低。与COVID-19相关的肺泡炎主要由先天效应物维持,其显示出广泛激活的特征。支气管肺泡环境中促炎细胞因子IL 6和IL 8的负荷与临床结果相关。在线版本包含补充材料,可通过10.1186/s12890-020-01343-z获得。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly reached pandemic proportions. Given that the main target of SARS-CoV-2 are lungs leading to severe pneumonia with hyperactivation of the inflammatory cascade, we conducted a prospective study to assess alveolar inflammatory status in patients with moderate to severe COVID-19. Diagnostic bronchoalveolar lavage (BAL) was performed in 33 adult patients with SARS-CoV-2 infection by real-time PCR on nasopharyngeal swab admitted to the Intensive care unit (ICU) (n = 28) and to the Intermediate Medicine Ward (IMW) (n = 5). We analyze the differential cell count, ultrastructure of cells and Interleukin (IL)6, 8 and 10 levels. ICU patients showed a marked increase in neutrophils (1.24 × 105 ml− 1, 0.85–2.07), lower lymphocyte (0.97 × 105 ml− 1, 0.024–0.34) and macrophages fractions (0.43 × 105 ml− 1, 0.34–1.62) compared to IMW patients (0.095 × 105 ml− 1, 0.05–0.73; 0.47 × 105 ml− 1, 0.28–1.01 and 2.14 × 105 ml− 1, 1.17–3.01, respectively) (p < 0.01). Study of ICU patients BAL by electron transmission microscopy showed viral particles inside mononuclear cells confirmed by immunostaining with anti-viral capsid and spike antibodies. IL6 and IL8 were significantly higher in ICU patients than in IMW (IL6 p < 0.01, IL8 p < 0.0001), and also in patients who did not survive (IL6 p < 0.05, IL8 p = 0.05 vs. survivors). IL10 did not show a significant variation between groups. Dividing patients by treatment received, lower BAL concentrations of IL6 were found in patients treated with steroids as compared to those treated with tocilizumab (p < 0.1) or antivirals (p < 0.05). Alveolitis, associated with COVID-19, is mainly sustained by innate effectors which showed features of extensive activation. The burden of pro-inflammatory cytokines IL6 and IL8 in the broncho-alveolar environment is associated with clinical outcome. The online version contains supplementary material available at 10.1186/s12890-020-01343-z.
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