EN
首页 资讯 期刊 导师 问答 求职 发Paper 文献直达 高级搜索 期刊列表
当前位置： X-MOL 学术 › Crit. Care › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Pneumocystis pneumonia risk among viral acute respiratory distress syndrome related or not to COVID 19
Critical Care ( IF 15.1 ) Pub Date : 2021-09-26 , DOI: 10.1186/s13054-021-03767-3
Keyvan Razazi 1, 2 , Romain Arrestier 1, 2, 3 , Anne Fleur Haudebourg 1, 2 , Francoise Botterel 4, 5 , Armand Mekontso Dessap 1, 2, 6 ,
Affiliation  

Lymphopenia, corticosteroids and immunomodulatory therapeutics frequently used in COVID-19 patients with acute respiratory distress syndrome (C-ARDS) may be contributing factors to opportunistic infection such as Pneumocystis jirovecii pneumonia (PCP).

We conducted a retrospective study to compare the prevalence of PCP between patients with C-ARDS and those with non-SARS-CoV-2 viral ARDS (NC-ARDS).

Methods and some data from this cohort have been previously published [1]. There was no systematic protocol to search for PCP but in case of suspicion of PCP (respiratory symptoms with any consistent radiographic features), several analyses were performed on respiratory samples, such as broncho-alveolar lavage (BAL), blind protected sample, or sputum. It included direct examination (using May-Grünwald Giemsa (MGG), or immunofluorescence staining), detection of Pneumocystis jirovecii DNA by real-time polymerase chain reaction (qPCR) [2], and serum (1–3)-β-D-glucan. During the COVID-19 outbreak, immunofluorescence staining was not performed. PCP was defined as per the revised EORTC/MSGERC definition [3] as follows: proven in case of suspicion with positive direct examination; possible in case of suspicion with positive qPCR and positive BDG in ≥ 2 consecutive serum samples provided other etiologies have been excluded. SARS-CoV-2 and other viruses were not considered a priori as host factors. Patients with positive qPCR but lacking the other criteria for possible PCP were classified as colonized.

The primary endpoint was the difference in prevalence of PCP between C-ARDS and NC-ARDS patients.

No statistical sample size calculation was performed a priori, and sample size was equal to the number of patients treated during the study period. All patients were included only once.

Between October 1, 2009, and April 29, 2020, ninety patients had C-ARDS (positive RT PCR test for SARS-CoV-2), while 82 patients had viral NC-ARDS. Our study comprises 120 patients with fungal analyses on respiratory samples obtained from 81 C-ARDS and 39 NC-ARDS patients. NC-ARDS patients had more comorbidities were more often immunocompromised, and had lower lymphocyte counts than C-ARDS patients (Table 1). C-ARDS patient received less steroid than NC-ARDS patients because they were included before randomized trials demonstrating decreased mortality with dexamethasone.

Table 1 Characteristics of patients with Pneumocystis jirovecii research according to C-ARDS and NC-ARDS patients
Full size table

Pneumocystis analyses were performed on a mean of 3.1 respiratory sample per patient (range 1–15). Direct examination was performed in a total of 72 samples, with two positive cases. qPCR was performed in a total of 368 samples (294 blind protected samples, 72 BAL, and three sputum). All qPCR were negative in C-ARDS patients, while five (13%) NC-ARDS patients had at least one positive PCR, with a median cycle threshold of 36.6 [30–38.3].

Two NC-ARDS patients fulfilled proven PCP diagnostic criteria, with a positive direct examination, a single ß-D-glucan > 80 pg/mL (Table 2), and received treatment for PCP.

Table 2 Characteristics of patients with a positive Pneumocystis jirovecii qPCR
Full size table

Three other NC-ARDS patients were classified as colonized, while no patient fulfilled possible PCP diagnostic criteria. Time between ICU admission and positive sample for PCP (Table 2) was short (< 2 days) like in other invasive fungal infections (i.e. invasive pulmonary aspergillosis) in severe influenza infection or ARDS.

In this study of patients with viral ARDS, we found a low risk for possible or proven PCP. Our findings are in accordance with two smaller studies in France [4, 5] retrieving a low risk of Pneumocystis colonisation in COVID-19 patients. In our cohort, qPCR was positive in 13% of NC-ARDS. This result is in accordance with a previous study showing 7% of positive qPCR in ICU-admitted influenza patients [6].

The strengths of our study are the analysis of a large ARDS cohort with fungal analyses. Our study also has limitations: monocentric design, NC-ARDS patients more frequently immunocompromised, and a long cohort period.

The datasets supporting the conclusions are included within the article.

C-ARDS:

Coronavirus disease 19 related acute respiratory distress syndrome

NC-ARDS:

Non-coronavirus disease 19 viral ARDS

PCP:

Pneumocystis jirovecii Pneumonia

  1. 1.

    Razazi K, Arrestier R, Haudebourg AF, Benelli B, Carteaux G, Decousser J-W, et al. Risks of ventilator-associated pneumonia and invasive pulmonary aspergillosis in patients with viral acute respiratory distress syndrome related or not to Coronavirus 19 disease. Crit Care Lond Engl. 2020;24:699.

    Article Google Scholar

  2. 2.

    Botterel F, Cabaret O, Foulet F, Cordonnier C, Costa J-M, Bretagne S. Clinical significance of quantifying Pneumocystis jirovecii DNA by using real-time PCR in bronchoalveolar lavage fluid from immunocompromised patients. J Clin Microbiol. 2012;50:227–31.

    CAS Article Google Scholar

  3. 3.

    Donnelly JP, Chen SC, Kauffman CA, Steinbach WJ, Baddley JW, Verweij PE, et al. Revision and update of the consensus definitions of invasive fungal disease from the european organization for research and treatment of cancer and the mycoses study group education and research consortium. Clin Infect Dis Off Publ Infect Dis Soc Am. 2020;71:1367–76.

    Article Google Scholar

  4. 4.

    Blaize M, Mayaux J, Luyt C-E, Lampros A, Fekkar A. COVID-19-related respiratory failure and lymphopenia do not seem associated with pneumocystosis. Am J Respir Crit Care Med. 2020;202:1734–6.

    CAS Article Google Scholar

  5. 5.

    Alanio A, Dellière S, Voicu S, Bretagne S, Mégarbane B. The presence of Pneumocystis jirovecii in critically ill patients with COVID-19. J Infect. 2020;

  6. 6.

    Beumer MC, Koch RM, van Beuningen D, OudeLashof AM, van de Veerdonk FL, Kolwijck E, et al. Influenza virus and factors that are associated with ICU admission, pulmonary co-infections and ICU mortality. J Crit Care. 2019;50:59–65.

    CAS Article Google Scholar

Download references

We thank Jean Hazebroucq and Francois Hemery, for their invaluable help. We are very indebted for the COVID-PCP group for the help in the data management and the review of the final manuscript. The COVID PCP group is composed by the followings members: Slim Fourati, Brice Benelli, Frédérique Boquel, Nicolas de Prost, Guillaume Carteaux, Jeanne Tran Van Nhieu, Frederic Schlemmer.

No funding was received for this study.

Author notes

  1. Keyvan Razazi, Romain Arrestier, Francoise Botterel, Armand Mekontso Dessap have equally contributed to this work

Affiliations

  1. Service de Médecine Intensive Réanimation, AP-HP (Assistance Publique-Hôpitaux de Paris), Hôpitaux Universitaires Henri Mondor, DMU Médecine, 94010, Créteil, France

    Keyvan Razazi, Romain Arrestier, Anne Fleur Haudebourg & Armand Mekontso Dessap

  2. Faculté de Santé de Créteil, IMRB, GRC CARMAS, UPEC (Université Paris Est Créteil), 94010, Créteil, France

    Keyvan Razazi, Romain Arrestier, Anne Fleur Haudebourg & Armand Mekontso Dessap

  3. Département de Virologie, Bactériologie, Parasitologie-Mycologie, AP-HP (Assistance Publique-Hôpitaux de Paris), Hôpitaux Universitaires Henri Mondor, 94010, Créteil, France

    Francoise Botterel

  4. EA 7380 Dynamic, UPEC, Ecole Nationale Vétérinaire d’Alfort, USC Anses, Créteil, France

    Francoise Botterel

  5. INSERM, Unité U955, France Université Paris Est, 94010, Créteil, France

    Armand Mekontso Dessap

  6. Service de Medecine Intensive Réanimation, CHU Henri Mondor, 51, Av de Lattre de Tassigny, 94000, Créteil Cedex, France

    Romain Arrestier

Authors
  1. Keyvan RazaziView author publications

    You can also search for this author in PubMed Google Scholar

  2. Romain ArrestierView author publications

    You can also search for this author in PubMed Google Scholar

  3. Anne Fleur HaudebourgView author publications

    You can also search for this author in PubMed Google Scholar

  4. Francoise BotterelView author publications

    You can also search for this author in PubMed Google Scholar

  5. Armand Mekontso DessapView author publications

    You can also search for this author in PubMed Google Scholar

Consortia

and the COVID PCP group

  • Slim Fourati
  • , Brice Benelli
  • , Frédérique Boquel
  • , Nicolas de Prost
  • , Guillaume Carteaux
  • , Jeanne Tran Van Nhieu
  •  & Frederic Schlemmer

Contributions

KR, RA and FB contributed to the study design, analysis and interpretation of data. KR, RA and AMD drafted the initial manuscript and approved the article final version. AFH, SF, AMD and the COVID-PCP group contributed to the interpretation of data, critical revision of intellectual content and approval of the submitted version of the article. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Romain Arrestier.

Ethics approval and consent to participate

This observational study was approved by the Ethical Review Board of the French Society for Intensive Care Medicine (Société de Réanimation de Langue Française). As per the French law, no informed consent was required for this type of studies.

Consent for publication

Not applicable.

Competing interests

All authors report no conflict of interest relevant to this study.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

Verify currency and authenticity via CrossMark

Cite this article

Razazi, K., Arrestier, R., Haudebourg, A.F. et al. Pneumocystis pneumonia risk among viral acute respiratory distress syndrome related or not to COVID 19. Crit Care 25, 348 (2021). https://doi.org/10.1186/s13054-021-03767-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s13054-021-03767-3

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative



中文翻译：
病毒性急性呼吸窘迫综合征与 COVID 19 相关或无关的肺孢子菌肺炎风险

经常用于患有急性呼吸窘迫综合征 (C-ARDS) 的 COVID-19 患者的淋巴细胞减少、皮质类固醇和免疫调节疗法可能是导致机会性感染的因素，例如Pneumocystis jirovecii肺炎 (PCP)。

我们进行了一项回顾性研究，比较了 C-ARDS 患者和非 SARS-CoV-2 病毒性 ARDS (NC-ARDS) 患者的 PCP 患病率。

该队列的方法和一些数据先前已发表[1]。没有搜索 PCP 的系统方案，但在怀疑 PCP（具有任何一致放射学特征的呼吸道症状）的情况下，对呼吸道样本进行了几项分析，例如支气管肺泡灌洗液 (BAL)、盲保护样本或痰液. 它包括直接检查（使用 May-Grünwald Giemsa (MGG) 或免疫荧光染色），检测Pneumocystis jirovecii通过实时聚合酶链反应 (qPCR) [2] 和血清 (1-3)-β-D-葡聚糖检测 DNA。在 COVID-19 爆发期间，未进行免疫荧光染色。PCP 根据修订后的 EORTC/MSGERC 定义 [3] 定义如下：在怀疑的情况下通过直接检查得到证实；如果怀疑 qPCR 阳性和 BDG 阳性 ≥ 2 个连续血清样本，但已排除其他病因。SARS-CoV-2 和其他病毒不被认为是先验的宿主因素。qPCR 阳性但缺乏其他可能的 PCP 标准的患者被归类为定植。

主要终点是 C-ARDS 和 NC-ARDS 患者之间 PCP 患病率的差异。

没有先验地进行统计样本量计算，样本量等于研究期间治疗的患者数量。所有患者仅纳入一次。

2009 年 10 月 1 日至 2020 年 4 月 29 日期间，90 名患者患有 C-ARDS（SARS-CoV-2 的 RT PCR 检测呈阳性），而 82 名患者患有病毒性 NC-ARDS。我们的研究包括 120 名患者，对从 81 名 C-ARDS 和 39 名 NC-ARDS 患者获得的呼吸道样本进行真菌分析。与 C-ARDS 患者相比，NC-ARDS 患者的合并症更多，免疫功能低下，淋巴细胞计数更低（表 1）。C-ARDS 患者接受的类固醇少于 NC-ARDS 患者，因为他们在随机试验之前被纳入，表明地塞米松可降低死亡率。

表 1 C-ARDS 和 NC-ARDS 患者的耶氏肺孢子菌研究特征
全尺寸表

肺孢子菌分析对每位患者平均 3.1 个呼吸样本（范围 1-15）进行。直接检查共72例，阳性2例。对总共 368 个样本（294 个盲保护样本、72 个 BAL 和 3 个痰液）进行了 qPCR。C-ARDS 患者的所有 qPCR 均为阴性，而 5 名 (13%) NC-ARDS 患者至少有一次 PCR 阳性，中位周期阈值为 36.6 [30-38.3]。

两名 NC-ARDS 患者符合经证实的 PCP 诊断标准，直接检查呈阳性，单个 ß-D-葡聚糖 > 80 pg/mL（表 2），并接受了 PCP 治疗。

表 2 Pneumocystis jirovecii qPCR阳性患者的特征
全尺寸表

其他三名 NC-ARDS 患者被归类为定植，而没有患者符合可能的 PCP 诊断标准。与严重流感感染或 ARDS 中的其他侵袭性真菌感染（即侵袭性肺曲霉病）一样，入住 ICU 和 PCP 阳性样本之间的时间（表 2）很短（< 2 天）。

在这项针对病毒性 ARDS 患者的研究中，我们发现可能或已证实的 PCP 风险较低。我们的研究结果与法国的两项较小的研究一致 [4, 5] 检索到 COVID-19 患者肺孢子菌定植的低风险。在我们的队列中，qPCR 在 13% 的 NC-ARDS 中呈阳性。这一结果与之前的一项研究一致，该研究显示 ICU 入院的流感患者中 7% 的 qPCR 阳性 [6]。

我们研究的优势在于通过真菌分析对大型 ARDS 队列进行分析。我们的研究也有局限性：单中心设计、NC-ARDS 患者更频繁地出现免疫功能低下以及较长的队列期。

支持结论的数据集包含在文章中。

牌：

冠状病毒病 19 相关的急性呼吸窘迫综合征

NC-ARDS：

非冠状病毒病 19 病毒性急性呼吸窘迫综合征

五氯苯酚：

肺孢子虫肺炎

  1. 1.

    Razazi K、Arrestier R、Haudebourg AF、Benelli B、Carteaux G、Decouser JW 等。与冠状病毒 19 病相关或不相关的病毒性急性呼吸窘迫综合征患者发生呼吸机相关性肺炎和侵袭性肺曲霉病的风险。Crit Care 伦敦 2020；24:699。

    文章谷歌学术

  2. 2.

    Botterel F、Cabaret O、Foulet F、Cordonnier C、Costa JM、Bretagne S.在免疫功能低下患者的支气管肺泡灌洗液中使用实时 PCR定量Pneumocystis jirovecii DNA 的临床意义。临床微生物学杂志。2012；50:227-31。

    CAS 文章 谷歌学术

  3. 3.

    Donnelly JP、Chen SC、Kauffman CA、Steinbach WJ、Baddley JW、Verweij PE 等。修订和更新欧洲癌症研究和治疗组织以及真菌病研究组教育和研究联盟对侵袭性真菌病的共识定义。Clin Infect Dis Off Publ Infect Dis Soc Am。2020；71：1367-76。

    文章谷歌学术

  4. 4.

    Blaize M、Mayaux J、Luyt CE、Lampros A、Fekkar A. COVID-19 相关的呼吸衰竭和淋巴细胞减少似乎与肺孢子虫病无关。Am J Respir Crit Care Med。2020；202：1734-6。

    CAS 文章 谷歌学术

  5. 5.

    Alanio A、Dellière S、Voicu S、Bretagne S、Mégarbane B. COVID-19 重症患者中存在耶氏肺孢子菌。Ĵ感染。2020；

  6. 6.

    Beumer MC、Koch RM、van Beuningen D、OudeLashof AM、van de Veerdonk FL、Kolwijck E 等。流感病毒和与入住 ICU、肺部合并感染和 ICU 死亡率相关的因素。J 暴击护理。2019；50:59–65。

    CAS 文章 谷歌学术

下载参考资料

我们感谢 Jean Hazebroucq 和 Francois Hemery 的宝贵帮助。我们非常感谢 COVID-PCP 小组在数据管理和最终手稿审查方面的帮助。COVID PCP 小组由以下成员组成：Slim Fourati、Brice Benelli、Frédérique Boquel、Nicolas de Prost、Guillaume Carteaux、Jeanne Tran Van Nhieu、Frederic Sc​​hlemmer。

这项研究没有收到任何资金。

作者笔记

  1. Keyvan Razazi、Romain Arrestier、Francoise Botterel、Armand Mekontso Dessap 对这项工作做出了同样的贡献

隶属关系

  1. Service de Médecine Intensive Réanimation, AP-HP (Assistance Publique-Hôpitaux de Paris), Hôpitaux Universitaires Henri Mondor, DMU Médecine, 94010, Créteil, France

    Keyvan Razazi、Romain Arrestier、Anne Fleur Haudebourg 和 Armand Mekontso Dessap

  2. Faculté de Santé de Créteil, IMRB, GRC CARMAS, UPEC (Université Paris Est Créteil), 94010, Créteil, France

    Keyvan Razazi、Romain Arrestier、Anne Fleur Haudebourg 和 Armand Mekontso Dessap

  3. Département de Virologie, Bactériologie, Parasitilogie-Mycologie, AP-HP (Assistance Publique-Hôpitaux de Paris), Hôpitaux Universitaires Henri Mondor, 94010, Créteil, France

    弗朗索瓦丝·博特雷尔

  4. EA 7380 Dynamic, UPEC, Ecole Nationale Vétérinaire d'Alfort, USC Anses, Créteil, France

    弗朗索瓦丝·博特雷尔

  5. INSERM, Unité U955, France Université Paris Est, 94010, Créteil, France

    阿曼德·梅孔佐·德萨普

  6. Service de Medecine Intensive Réanimation, CHU Henri Mondor, 51, Av de Lattre de Tassigny, 94000, Créteil Cedex, France

    罗曼·雷斯蒂尔

作者
  1. Keyvan Razazi查看作者的出版物

    您也可以在PubMed  Google Scholar中搜索该作者

  2. Romain Arrestier查看作者的出版物

    您也可以在PubMed  Google Scholar中搜索该作者

  3. Anne Fleur Haudebourg查看作者的出版物

    您也可以在PubMed  Google Scholar中搜索该作者

  4. Francoise Botterel查看作者的出版物

    您也可以在PubMed  Google Scholar中搜索该作者

  5. Armand Mekontso Dessap查看作者的出版物

    您也可以在PubMed  Google Scholar中搜索该作者

财团

和 COVID PCP 组

  • 苗条的弗拉蒂
  • , 布莱斯·贝内利
  • , 弗雷德里克·博克尔
  • , 尼古拉斯·德·普罗斯特
  • , 纪尧姆·卡托
  • , 珍妮·陈文纽
  •  & 弗雷德里克·施莱默

贡献

KR、RA 和 FB 为研究设计、数据分析和解释做出了贡献。KR、RA 和 AMD 起草了最初的手稿并批准了文章的最终版本。AFH、SF、AMD 和 COVID-PCP 小组为数据解释、知识内容的关键修订和文章提交版本的批准做出了贡献。所有作者阅读并认可的终稿。

通讯作者

与 Romain Arrestier 的通信。

伦理批准和同意参与

这项观察性研究得到了法国重症监护医学协会 ( Société de Réanimation de Langue Française ) 伦理审查委员会的批准。根据法国法律，此类研究不需要知情同意。

同意发表

不适用。

利益争夺

所有作者均报告没有与本研究相关的利益冲突。

出版商注

Springer Nature 对出版地图和机构附属机构的管辖权主张保持中立。

开放存取本文根据知识共享署名 4.0 国际许可进行许可，该许可允许以任何媒介或格式使用、共享、改编、分发和复制，只要您对原作者和来源给予适当的信任，并提供链接到知识共享许可，并说明是否进行了更改。本文中的图像或其他第三方材料包含在文章的知识共享许可中，除非在材料的信用额度中另有说明。如果文章的知识共享许可中未包含材料，并且您的预期用途不受法律法规的允许或超出允许的用途，则您需要直接从版权所有者那里获得许可。要查看此许可证的副本，请访问 http://creativecommons.org/licenses/by/4.0/。

转载和许可

通过 CrossMark 验证货币和真实性

引用这篇文章

Razazi, K., Arrestier, R., Haudebourg, AF等。 病毒性急性呼吸窘迫综合征与 COVID 19 相关或无关的肺孢子菌肺炎风险。Crit Care 25, 348 (2021)。https://doi.org/10.1186/s13054-021-03767-3

下载引文

  • 收到：

  • 接受：

  • 发表：

  • DOI ：https ://doi.org/10.1186/s13054-021-03767-3

分享这篇文章

与您共享以下链接的任何人都可以阅读此内容：

抱歉，本文目前没有可共享的链接。

由 Springer Nature SharedIt 内容共享计划提供
更新日期：2021-09-28
  点击分享   查看原文
点击收藏
阅读更多本刊最新论文 本刊介绍/投稿指南
down
wechat
bug