The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity

被引：361

作者：

Osuchowski, Marcin F. ^{[1
]}

Winkler, Martin S. ^{[2
]}

Skirecki, Tomasz ^{[3
]}

Cajander, Sara ^{[4
]}

Shankar-Hari, Manu ^{[5
,6
]}

Lachmann, Gunnar ^{[7
,9
]}

Monneret, Guillaume ^{[10
,11
]}

Venet, Fabienne ^{[10
,11
]}

Bauer, Michael ^{[12
,13
]}

Brunkhorst, Frank M. ^{[12
,13
,14
]}

Weis, Sebastian ^{[12
,13
,15
]}

Garcia-Salido, Alberto ^{[16
]}

Kox, Matthijs ^{[17
,18
]}

Cavaillon, Jean-Marc ^{[19
]}

Uhle, Florian ^{[20
]}

Weigand, Markus A. ^{[20
]}

Flohe, Stefanie B. ^{[21
]}

Wiersinga, W. Joost ^{[22
,23
]}

Almansa, Raquel ^{[24
,25
]}

de la Fuente, Amanda ^{[24
]}

Martin-Loeches, Ignacio ^{[26
]}

Meisel, Christian ^{[8
,27
]}

Spinetti, Thibaud ^{[28
]}

Schefold, Joerg C. ^{[28
]}

Cilloniz, Catia ^{[29
]}

Torres, Antoni ^{[25
,29
,30
]}

Giamarellos-Bourboulis, Evangelos J. ^{[31
]}

Ferrer, Ricard ^{[25
,32
,33
]}

Girardis, Massimo ^{[34
]}

Cossarizza, Andrea ^{[35
]}

Netea, Mihai G. ^{[17
,18
,36
,37
]}

van der Poll, Tom ^{[22
,23
]}

Bermejo-Martin, Jesus F. ^{[24
,25
]}

Rubio, Ignacio ^{[12
,13
]}

机构：

[1] AUVA Res Ctr, Ludwig Boltzmann Inst Expt & Clin Traumatol, Vienna, Austria

[2] Georg August Univ Gottingen, Univ Gottingen, Dept Anaesthesiol, Med Ctr, Gottingen, Germany

[3] Ctr Postgrad Med Educ, Lab Flow Cytometry, Warsaw, Poland

[4] Orebro Univ, Fac Med & Hlth, Dept Infect Dis, Orebro, Sweden

[5] Guys & St Thomas NHS Fdn Trust, ICU Support Off, St Thomas Hosp, London, England

[6] Kings Coll London, Sch Immunol & Microbial Sci, London, England

[7] Charite Univ Med Berlin, Dept Anesthesiol & Operat Intens Care Med CCM CVK, Berlin, Germany

[8] Charite Univ Med Berlin, Inst Med Immunol, Berlin, Germany

[9] Berlin Inst Hlth, Berlin, Germany

[10] Hop Edouard Herriot, Hosp Civils Lyon, Immunol Lab, Lyon, France

[11] Univ Laude Bernard Lyon 1, Pathophysiol Injury Induced Immunosuppress, Equipe Accueil 2426, BioMirieux,Hosp Civets Lyon,Hop Edouard Herriot, Lyon, France

[12] Friedrich Schiller Univ, Jena Univ Hosp, Dept Anesthesiol & Intens Care Med, Jena, Germany

[13] Friedrich Schiller Univ, Jena Univ Hosp, Ctr Sepsis Control & Care, Jena, Germany

[14] Friedrich Schiller Univ, Jena Univ Hosp, Ctr Clin Studies, Jena, Germany

[15] Friedrich Schiller Univ, Jena Univ Hosp, Inst Infect Dis & Infect Control, Jena, Germany

[16] Hosp Infanta Univ Nino Jesus, Pediat Crit Care Unit, Madrid, Spain

[17] Radboud Univ Nijmegen, Med Ctr, Dept Intens Care Med, Nijmegen, Netherlands

[18] Radboud Univ Nijmegen, Med Ctr, Radboud Ctr Infect Dis, Nijmegen, Netherlands

[19] Agence Natl Rech, Paris, France

[20] Heidelberg Univ Hosp, Dept Anesthesiol, Heidelberg, Germany

[21] Univ Duisburg Essen, Univ Hosp Essen, Dept Trauma Hand & Reconstruct Surg, Essen, Germany

[22] Univ Amsterdam, Div Infect Dis, Amsterdam Univ, Med Ctr,Locat Acad Med Ctr, Amsterdam, Netherlands

[23] Univ Amsterdam, Ctr Expt & Mol Med, Amsterdam Univ, Med Ctr,Locat Acad Med Ctr, Amsterdam, Netherlands

[24] Hosp Univ Rio Hortega Valladolid, Grp Biomed Res Sepsis, Inst Invest Biomed Salamanca, Salamanca, Spain

[25] Inst Salud Cados III, Ctr Invest Biomed Red Enfermedades Resp, Madrid, Spain

[26] St James Hosp, Multidisciplinary Intens Care Res Org, Dublin, Ireland

[27] Lab Berlin Charite Vivantes, Dept Immunol, Berlin, Germany

[28] Univ Bern, Bern Univ Hosp, Dept Intens Care Med, Inselspital, Bern, Switzerland

[29] Univ Barcelona, Inst Invest Biomed August Pi & Sunyer, Hosp Clin Barcelona, Resp Inst,Pneumol Dept,ICREA,CIBERESUCICOVID, Barcelona, Spain

[30] SGR 911 ICREA Acad, Barcelona, Spain

[31] Natl & Kapodistrian Univ Athens, Med Sch, Dept Internal Med 4, Athens, Greece

[32] Vall dHebron Barcelona Hosp Campus, Intens Care Dept, Vall dHebron Univ Hosp, Barcelona, Spain

[33] Vall dHebron Barcelona Hosp Campus, Shock Organ Dysfunct & Resuscitat Res Grp, Vall dHebron Univ Hosp, Barcelona, Spain

[34] Univ Hosp Modena, Dept Anesthesia & Intens Care, Modena, Italy

[35] Univ Modena & Reggio Emilia, Dept Med & Surg Sci Children & Adults, Modena, Italy

[36] Craiova Univ Med & Pharm, Human Genom Lab, Craiova, Romania

[37] Univ Bonn, Dept Immunol & Metab, Life & Med Sci Inst, Bonn, Germany

来源：

LANCET RESPIRATORY MEDICINE | 2021年 / 9卷 / 06期

关键词：

ACUTE RESPIRATORY SYNDROME; ANTIGEN-DR EXPRESSION; HUMAN CORONAVIRUSES 229E; PERIPHERAL-BLOOD; SEPTIC SHOCK; HLA-DR; CLINICAL CHARACTERISTICS; COMPLEMENT ACTIVATION; CROSS-REACTIVITY; DOWN-REGULATION;

D O I：

10.1016/S2213-2600(21)00218-6

中图分类号：

R4 [临床医学];

学科分类号：

1002 ; 100602 ;

摘要：

The zoonotic SARS-CoV-2 virus that causes COVID-19 continues to spread worldwide, with devastating consequences. While the medical community has gained insight into the epidemiology of COVID-19, important questions remain about the clinical complexities and underlying mechanisms of disease phenotypes. Severe COVID-19 most commonly involves respiratory manifestations, although other systems are also affected, and acute disease is often followed by protracted complications. Such complex manifestations suggest that SARS-CoV-2 dysregulates the host response, triggering wide-ranging immuno-inflammatory, thrombotic, and parenchymal derangements. We review the intricacies of COVID-19 pathophysiology, its various phenotypes, and the anti-SARS-CoV-2 host response at the humoral and cellular levels. Some similarities exist between COVID-19 and respiratory failure of other origins, but evidence for many distinctive mechanistic features indicates that COVID-19 constitutes a new disease entity, with emerging data suggesting involvement of an endotheliopathy-centred pathophysiology. Further research, combining basic and clinical studies, is needed to advance understanding of pathophysiological mechanisms and to characterise immuno-inflammatory derangements across the range of phenotypes to enable optimum care for patients with COVID-19.

引用

页码：622 / 642

页数：21

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