今天我们继续来精读南开大学校长中国科学院曹雪涛院士发表在Nature Review Immunology（影响因子44）的一篇综述，题目为“COVID-19: immunopathology and its implications for therapy”，文章系统总结新冠病毒产生免疫学反应及治疗方法。首先我们复盘一下上次学习的词组：Immunopathology 免疫病理学；implication可能的影响或结果；implications for therapy 为对治疗的影响；Be characterized by为以…为特征；Pneumonia肺炎；cytokine storm炎症因子风暴；clinical management 临床管理；Pandemic大流行；Mild, moderate, severe轻度的、中度的和重度的；and/or和(或)；mainstay支柱；mechanical ventilation机械通气；block viral entry 阻断病毒入侵；a major focus主要关注点；locally and systemically局部的和系统全身性的；a common feature一个共同点；Severity严重性；poor clinical outcome临床治疗效果查；Convalescent恢复期的；Normalize正常化。
1. ①Convalescentplasma containingneutralizing antibodieshas beenused to treat a small number of patients with severe disease, and preliminaryresults show clinical improvement in 5 of 5 critically ill patients with COVID-19who developed ARDS.②High- throughput platforms, such as the large- scale single- cell RNA sequencing of B cells (enriched for B cells that produce antibodies directed at the SARS- CoV-2 spike glycoprotein) from patients who are convalescent, have allowed the identification of SARS- CoV-2- specific neutralizing antibodies.
含有中和抗体的恢复性血浆已用于治疗少数重症患者，初步结果显示，在5名发展为ARDS的COVID-19重症患者中，有5名的临床改善。高通量平台，例如来自康复期患者的B细胞的大规模单细胞RNA测序（富含产生针对SARS-CoV-2穗状糖蛋白的抗体的B细胞），已经可以鉴定SARS -CoV-2-特异性中和抗体。
段落分析：本段的主要讲述了抗体治疗。①介绍了治疗现状，②介绍了科研现状。
Convalescent /kɒnvə'les(ə)nt/ 形容词，解释为恢复期的（someone who is spending time getting well after an illness）。例句： The result of the study was an “identifying e-usage” experience category, which refers to the rehabilitees’ notions of the use of information and communication technologies (e-usage) in the process of behavior change.
这项研究的结果是一个“识别电子使用”的经验类别，它指的是康复者在行为改变过程中使用信息和通信技术(电子使用)的概念。
neutralizing antibodies 词组，解释为中和抗体。中和抗体是当病原微生物侵入机体时会产生相应的抗体。病原微生物入侵细胞时需要依赖病原体自身表达的特定分子与细胞上的受体结合，才能感染细胞，并进一步扩增。中和抗体是B淋巴细胞产生的某些抗体，能够与病原微生物表面的抗原结合，从而阻止该病原微生物黏附靶细胞受体，防止侵入细胞。【科普知识】
preliminary /prɪ'lɪmɪn(ə)rɪ/ 形容词，解释为初步的（happening before a more important action or event）。词组preliminary
results / findings / enquiries 初步结果 / 发现 / 调查。
High- throughput 复合形容词，解释为大规模的。
2. ①The detectionof SARS- CoV-2- specific IgM and IgG in patients provided the basis for disease diagnosis, in conjunction with RT- PCR- based tests.②However, two studies, based on the analysis of 222 and 173 patients with COVID-19, respectively, reported that patients with severe disease frequently had an increased IgG response and a higher titre of total antibodies, which was associated with worse outcome. This was suggestive of possible antibody- dependent enhancement (ADE) of SARS- CoV-2 infection. ③The immunopathological effects of ADE have been observed in various viral infections, characterized as antibody- mediated enhancement of viral entry and induction of a severe inflammatory response. ④Worryingly, it was shown that a neutralizing monoclonal antibody targeting the receptor- binding domain of the spike protein of the related Middle East respiratory syndrome (MERS) virus can enhance viral entry. ⑤A potential pathogenic effect of antibodies targeted at SARS- CoV-2 would be of major concern for vaccine development and antibody- based therapies. ⑥Additional independent large- cohort studies are needed to substantiate or dismiss this possibility.
结合基于RT-PCR的检测，对患者SARS-CoV-2-特异性IgM和IgG的检测为疾病诊断提供了基础。但是，两项分别基于222例和173例COVID-19的分析的研究报告中指出，患有严重疾病的患者通常IgG应答增加且总抗体滴度更高，这与较差的预后相关。这暗示了SARS-CoV-2感染的可能的抗体依赖性增强（ADE）。在各种病毒感染中已经观察到ADE的免疫病理学作用，其特征在于抗体介导的病毒进入增强和严重炎症反应的诱导。令人担忧的是，已表明靶向相关中东呼吸综合征（MERS）病毒刺突蛋白受体结合域的中和性单克隆抗体可增强病毒进入。靶向SARS-CoV-2的抗体的潜在致病作用将是疫苗开发和基于抗体的疗法的主要关注点。需要进行额外的独立大型队列研究来证实或消除这种可能性。
段落分析：本段紧接着上一段，介绍了抗体依赖性的增强（ADE）。 ①-③介绍了目前研究的现状，④介绍了ADE的担忧，就是增强病毒入侵。⑤-⑥介绍了临床治疗的可能性。
provide the basis for sth 词组，解释为提供了基础。例句：These databases provide a fundamental basis for studies of liver cancer outcomes.这些数据库为肝癌结果的研究提供了基础。
in conjunction with词组，解释为结合，可以替换为combined with。例句：Probiotics are generally orally administered to infants in conjunction with enteral feeds. 益生菌通常与肠内饲料一起口服给婴儿。
Respectively /rɪ'spektɪvlɪ/ 副词，解释为分别的，各自的（in the same order as the people or things already mentioned）。例句：Briefly, splicing results in two mRNA transcripts that code for VP1 or for VP2/3, respectively. 简单地说，剪接导致两个mRNA转录本，分别编码VP1或VP2/3。
Titre/'taɪtə/名词，解释为滴度。可以替换为concentration。
worse outcome 词组，解释为预后较差。例句：Acidosis is the most common acid-base disturbance, with metabolic acidosis potentially indicating a more severe course and worse outcome.酸中毒是最常见的酸碱紊乱，代谢性酸中毒可能预示着更严重的过程和更糟糕的结果。
This was suggestive of 写作句型，理解为这暗示了…,例句：this was suggestive of a bird's nest.这暗示着燕窝。【写作推荐】
Worryingly /'wʌriiŋli/ 副词，解释为令人担忧的。例句：Worryingly, polymyxin- and tigecycline-resistant A. baumannii strains have been isolated in many places around the world .令人担忧的是，多粘菌素和抗地霉素的鲍曼氏杆菌菌株已经在世界各地被分离出来。
vaccine /'væksiːn/ 名词，解释为疫苗（a substance that is put into the blood and that protects the body from a disease）。疫苗是指用各类病原微生物制作的用于预防接种的生物制品。其中用细菌或螺旋体制作的疫苗亦称为菌苗。疫苗分为活疫苗和死疫苗两种。常用的活疫苗有卡介苗，脊髓灰质炎疫苗、麻疹疫苗、鼠疫菌苗等。常用的死疫苗有百日咳菌苗、伤寒菌苗、流脑菌苗、霍乱菌苗等。【科普知识】
large- cohort study 词组，大型队列研究。队列研究是将某一特定人群按是否暴露于某可疑因素或暴露程度分为不同的亚组，追踪观察两组或多组成员结局（如疾病）发生的情况，比较各组之间结局发生率的差异，从而判定这些因素与该结局之间有无因果关联及关联程度的一种观察性研究方法。【科普知识】
substantiate or dismiss 词组，解释为证实或者消除，substantiate 可以替换为affirm, confirm, corroborate, support, sustain，例句：This case substantiate that FMT can be a promising treatment for HM. 这个病例证实了FMT是治疗HM的一种很有前途的方法。Patients may be unaware of or dismiss mental health symptoms, or present with somatic symptoms such as headaches, muscle aches, fatigue, or heart palpitations. 患者可能不知道或忽视心理健康症状，或出现身体症状，如头痛、肌肉疼痛、疲劳或心悸。
3. ①Most patientswith severe COVID-19 exhibitsubstantiallyelevatedserum levels of pro- inflammatory cytokines including IL-6 and IL-1β, as wellas IL-2, IL-8, IL-17, G- CSF, GM- CSF, IP10, MCP1, MIP1α (also known as CCL3)and TNF, characterized as cytokine storm1–4.②Also, C- reactive protein and D- dimer are found to be abnormally high. ③High levels of pro- inflammatory cytokines may lead to shock and tissue damage in the heart, liver and kidney, as well as respiratory failure or multiple organ failure. ④They also mediate extensive pulmonary pathology, leading to massive infiltration of neutrophils and macrophages, diffuse alveolar damage with the formation of hyaline membranes and a diffuse thickening of the alveolar wall. ⑤Spleen atrophy and lymph node necrosis were also observed, indicative of immune- mediated damage in deceased patients.
大多数严重COVID-19的患者表现出血清促炎性细胞因子的水平显着升高，包括IL-6和IL-1β以及IL-2，IL-8，IL-17，G-CSF，GM-CSF，IP10 ，MCP1，MIP1α（也称为CCL3）和TNF，特征为细胞因子storm1-4。而且，发现C-反应蛋白和D-二聚体异常高。高水平的促炎细胞因子可能导致心脏，肝脏和肾脏的休克和组织损伤，以及呼吸衰竭或多器官衰竭。它们还介导广泛的肺部病理，导致嗜中性粒细胞和巨噬细胞大量浸润，弥漫性肺泡损伤以及透明膜的形成以及肺泡壁的弥漫性增厚。还观察到脾萎缩和淋巴结坏死，表明死者的免疫介导损害。
段落分析：本段介绍了新冠病毒病人体内的免疫失稳态情况。①介绍了炎症因子，②介绍了C反应蛋白和D二聚体，③-④ 介绍了促炎因子及其器官损伤，⑤介绍了脾萎缩和淋巴结坏死表明了炎症损伤的证据。
Substantially 副词，解释为显著地（very much; a lot），可以替换为considerably。
Elevated/'elɪveɪtɪd/形容词，解释为升高的（formalelevated levels, temperatures etc are higher than normal），词汇拓展：↓, diminished; ↑, elevated; +, enhancing. 治疗，减少；治疗，升高；+，增强。
Abnormally /æb'nɔ:məli/ 副词，解释为异常地。例句：The tumors can cause abnormally high glucagon level. 肿瘤可引起胰高血糖素水平异常高。
Pulmonary/'pʌlmən(ə)rɪ/形容词，解释为肺部的（connected with the lungs）。例句：Multiple pulmonary nodules, pulmonary infiltrates and pulmonary alveolar hemorrhage are common manifestations in the lung. 多发肺结节、肺浸润、肺泡出血是肺部常见表现。
massive infiltration 词组，解释为广泛浸润。例句：Regeneration and massive leukocyte infiltration were detected in the muscle. 在肌肉中检测到再生和大量白细胞浸润。
diffuse alveolar damage 词组，解释为弥漫性的肺泡损伤。英文释义：Diffuse alveolar damage is a histological pattern in lung disease. It is seen in acute respiratory distress syndrome (ARDS), transfusion related acute lung injury (TRALI) and acute interstitial pneumonia (AIP). 弥漫性肺泡损伤是肺部疾病的一种组织学模式。在急性呼吸窘迫综合征（ARDS），与输血有关的急性肺损伤（TRALI）和急性间质性肺炎（AIP）中可见到。【科普知识】
hyaline membrane 词组，解释为透明膜。词组：Neonatal hyaline membrane disease: 新生儿肺透明膜病clinical hyaline membrane disease: 临床透明膜病。
diffuse thickening of the alveolar wall 词组，解释为肺泡壁的弥漫性增厚。
Spleen atrophy 词组，解释为脾萎缩。慢性右心衰竭：心脏瓣膜病发生慢性右心衰竭时，脾脏常不仅不因静脉瘀血而肿大，反而常因缺氧而发生脾萎缩。【科普知识】
lymph node necrosis 词组，解释为淋巴结坏死。例句：Untreated infections evolve to colliquative necrosis with lymph node tenderness (stage II), and subsequent cutaneous involvement leading to a violaceous discoloration of the overlying skin (stage III). 未经治疗的感染演变为伴有淋巴结压痛的结缔组织坏死(II期)，随后皮肤受累导致上覆皮肤紫红色变色(Ⅲ期)。
Be indicative of 词组，解释为表明、指出。例句：A TRPG ≥ 36 mmHg is indicative of PH. 一个TRPG≥36mm Hg表示PH值。
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