Atypical response to bacterial coinfection and persistent neutrophilic bronchoalveolar inflammation distinguish critical COVID-19 from influenza.
Atypical response to bacterial coinfection and persistent neutrophilic bronchoalveolar inflammation distinguish critical COVID-19 from influenza.
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对细菌合并感染的非典型反应和持续性中性粒细胞性支气管肺泡炎症将危重的 COVID-19 与流感区分开来。
DOI：
10.1172/jci.insight.155055
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发表时间：
2022-01-11
期刊：
影响因子：
8
通讯作者：
Proost P
中科院分区：
文献类型：
--
作者：
Cambier S;Metzemaekers M;de Carvalho AC;Nooyens A;Jacobs C;Vanderbeke L;Malengier-Devlies B;Gouwy M;Heylen E;Meersseman P;Hermans G;Wauters E;Wilmer A;CONTAGIOUS Consortium;Schols D;Matthys P;Opdenakker G;Marques RE;Wauters J;Vandooren J;Proost P
中性粒细胞被认为是 2019 年严重冠状病毒病 (COVID-19) 病理生理学中重要的循环效应细胞。然而，它们在发炎肺部中的作用尚不完全清楚。在这里，我们收集了需要有创机械通气的危重 COVID-19 患者的支气管肺泡灌洗 (BAL) 液体和平行血液样本，并将 BAL 液体参数与机械通气流感患者的参数进行比较，作为非 COVID-19 病毒性肺炎队列。与流感患者相比，COVID-19患者的BAL液中过度活化的脱颗粒中性粒细胞数量增加，细胞因子IL-1β、IL-1RA、IL-17A、TNF-α和G-CSF浓度升高；趋化因子 CCL7、CXCL1、CXCL8、CXCL11 和 CXCL12α；以及蛋白酶抑制剂 elafin、分泌性白细胞蛋白酶抑制剂和金属蛋白酶组织抑制剂 1。相比之下，COVID-19 和流感 BAL 液中的 α-1 抗胰蛋白酶水平和净蛋白水解活性相当。在对细菌合并感染进行抗生素治疗期间，在 COVID-19 患者中检测到单核细胞、淋巴细胞和 NK 细胞的几种激活和趋化因子的 BAL 液水平升高，而在流感患者中浓度趋于下降，这突显了对 COVID-19 合并感染的持续免疫反应。最后，COVID-19 肺部的高蛋白水解活性表明考虑将蛋白酶抑制剂作为一种治疗选择。
Neutrophils are recognized as important circulating effector cells in the pathophysiology of severe coronavirus disease 2019 (COVID-19). However, their role within the inflamed lungs is incompletely understood. Here, we collected bronchoalveolar lavage (BAL) fluids and parallel blood samples of critically ill COVID-19 patients requiring invasive mechanical ventilation and compared BAL fluid parameters with those of mechanically ventilated patients with influenza, as a non–COVID-19 viral pneumonia cohort. Compared with those of patients with influenza, BAL fluids of patients with COVID-19 contained increased numbers of hyperactivated degranulating neutrophils and elevated concentrations of the cytokines IL-1β, IL-1RA, IL-17A, TNF-α, and G-CSF; the chemokines CCL7, CXCL1, CXCL8, CXCL11, and CXCL12α; and the protease inhibitors elafin, secretory leukocyte protease inhibitor, and tissue inhibitor of metalloproteinases 1. In contrast, α-1 antitrypsin levels and net proteolytic activity were comparable in COVID-19 and influenza BAL fluids. During antibiotic treatment for bacterial coinfections, increased BAL fluid levels of several activating and chemotactic factors for monocytes, lymphocytes, and NK cells were detected in patients with COVID-19 whereas concentrations tended to decrease in patients with influenza, highlighting the persistent immunological response to coinfections in COVID-19. Finally, the high proteolytic activity in COVID-19 lungs suggests considering protease inhibitors as a treatment option.
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影响因子：
12.3
作者：
Aschenbrenner AC;Mouktaroudi M;Krämer B;Oestreich M;Antonakos N;Nuesch-Germano M;Gkizeli K;Bonaguro L;Reusch N;Baßler K;Saridaki M;Knoll R;Pecht T;Kapellos TS;Doulou S;Kröger C;Herbert M;Holsten L;Horne A;Gemünd ID;Rovina N;Agrawal S;Dahm K;van Uelft M;Drews A;Lenkeit L;Bruse N;Gerretsen J;Gierlich J;Becker M;Händler K;Kraut M;Theis H;Mengiste S;De Domenico E;Schulte-Schrepping J;Seep L;Raabe J;Hoffmeister C;ToVinh M;Keitel V;Rieke G;Talevi V;Skowasch D;Aziz NA;Pickkers P;van de Veerdonk FL;Netea MG;Schultze JL;Kox M;Breteler MMB;Nattermann J;Koutsoukou A;Giamarellos-Bourboulis EJ;Ulas T;German COVID-19 Omics Initiative (DeCOI)
通讯作者：
German COVID-19 Omics Initiative (DeCOI)
影响因子：
3.1
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
通讯作者：
Meloni F
影响因子：
6.9
作者：
Houghton, A. McGarry
通讯作者：
Houghton, A. McGarry
DOI：
10.1016/j.xcrm.2021.100229
发表时间：
2021-04-20
期刊：
Cell reports. Medicine
影响因子：
--
作者：
Buehler PK;Zinkernagel AS;Hofmaenner DA;Wendel Garcia PD;Acevedo CT;Gómez-Mejia A;Mairpady Shambat S;Andreoni F;Maibach MA;Bartussek J;Hilty MP;Frey PM;Schuepbach RA;Brugger SD
通讯作者：
Brugger SD
影响因子：
8.3
作者：
Cardinal-Fernandez, Pablo;Lorente, Jose A.;Matute-Bello, Gustavo
通讯作者：
Matute-Bello, Gustavo