Complex Immune Dysregulation in COVID-19 Patients with Severe Respiratory Failure

被引：1521

作者：

Giamarellos-Bourboulis, Evangelos J. ^{[1
]}

Netea, Mihai G. ^{[2
,3
,4
]}

Rovina, Nikoletta ^{[5
,6
]}

Akinosoglou, Karolina ^{[7
]}

Antoniadou, Anastasia ^{[1
]}

Antonakos, Nikolaos ^{[1
]}

Damoraki, Georgia ^{[1
]}

Gkavogianni, Theologia ^{[1
]}

Adami, Maria-Evangelia ^{[1
]}

Katsaounou, Paraskevi ^{[8
]}

Ntaganou, Maria ^{[5
,6
]}

Kyriakopoulou, Magdalini ^{[5
,6
]}

Dimopoulos, George ^{[9
]}

Koutsodimitropoulos, Ioannis ^{[10
]}

Velissaris, Dimitrios ^{[7
]}

Koufargyris, Panagiotis ^{[1
]}

Karageorgos, Athanassios ^{[1
]}

Katrini, Konstantina ^{[1
]}

Lekakis, Vasileios ^{[1
]}

Lupse, Mihaela ^{[11
]}

Kotsaki, Antigone ^{[1
]}

Renieris, George ^{[1
]}

Theodoulou, Danai ^{[5
,6
]}

Panou, Vassiliki ^{[5
,6
]}

Koukaki, Evangelia ^{[5
,6
]}

Koulouris, Nikolaos ^{[5
,6
]}

Gogos, Charalambos ^{[7
]}

Koutsoukou, Antonia ^{[5
,6
]}

机构：

[1] Natl & Kapodistrian Univ Athens, Med Sch, Dept Internal Med 4, Athens 12462, Greece

[2] Univ Bonn, Life & Med Sci Inst, Immunol & Metab, D-53115 Bonn, Germany

[3] Radboud Univ Nijmegen, Dept Internal Med, NL-6500 Nijmegen, Netherlands

[4] Radboud Univ Nijmegen, Ctr Infect Dis, NL-6500 Nijmegen, Netherlands

[5] Natl & Kapodistrian Univ Athens, Med Sch, Dept Pulm Med 1, Athens 11527, Greece

[6] Natl & Kapodistrian Univ Athens, Med Sch, Intens Care Unit, Athens 11527, Greece

[7] Univ Patras, Med Sch, Dept Internal Med, Rion 26504, Greece

[8] Natl & Kapodistrian Univ Athens, Med Sch, Dept Crit Care Med 1, Athens 10676, Greece

[9] Natl & Kapodistrian Univ Athens, Med Sch, Dept Crit Care Med 2, Athens 12462, Greece

[10] Gen Hosp Elefsis Latseion, Interns Care Unit, Elefsis 19600, Greece

[11] Univ Med & Pharm, Dept Infect Dis, Cluj Napoca, Romania

来源：

CELL HOST & MICROBE | 2020年 / 27卷 / 06期

基金：

欧盟地平线“2020”;

关键词：

EXPRESSION; CELLS;

D O I：

10.1016/j.chom.2020.04.009

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

Proper management of COVID-19 mandates better understanding of disease pathogenesis. The sudden clinical deterioration 7-8 days after initial symptom onset suggests that severe respiratory failure (SRF) in COVID-19 is driven by a unique pattern of immune dysfunction. We studied immune responses of 54 COVID-19 patients, 28 of whom had SRF. All patients with SRF displayed either macrophage activation syndrome (MAS) or very low human leukocyte antigen D related (HLA-DR) expression accompanied by profound depletion of CD4 lymphocytes, CD19 lymphocytes, and natural killer (NK) cells. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) production by circulating monocytes was sustained, a pattern distinct from bacterial sepsis or influenza. SARS-CoV-2 patient plasma inhibited HLA-DR expression, and this was partially restored by the IL-6 blocker Tocilizumab; off-label Tocilizumab treatment of patients was accompanied by increase in circulating lymphocytes. Thus, the unique pattern of immune dysregulation in severe COVID-19 is characterized by IL-6-mediated low HLA-DR expression and lymphopenia, associated with sustained cytokine production and hyper-inflammation.

引用

页码：992 / +

页数：12

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