PMID- 32320677
OWN - NLM
STAT- MEDLINE
DCOM- 20200619
LR  - 20210110
IS  - 1934-6069 (Electronic)
IS  - 1931-3128 (Print)
IS  - 1931-3128 (Linking)
VI  - 27
IP  - 6
DP  - 2020 Jun 10
TI  - Complex Immune Dysregulation in COVID-19 Patients with Severe Respiratory 
      Failure.
PG  - 992-1000.e3
LID - S1931-3128(20)30236-5 [pii]
LID - 10.1016/j.chom.2020.04.009 [doi]
AB  - 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.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Giamarellos-Bourboulis, Evangelos J
AU  - Giamarellos-Bourboulis EJ
AD  - 4(th) Department of Internal Medicine, National and Kapodistrian University of 
      Athens, Medical School, 124 62 Athens, Greece. Electronic address: 
      egiamarel@med.uoa.gr.
FAU - Netea, Mihai G
AU  - Netea MG
AD  - Immunology and Metabolism, Life & Medical Sciences Institute, University of Bonn, 
      53115 Bonn, Germany; Department of Internal Medicine and Center for Infectious 
      Diseases, Radboud University, 6500 Nijmegen, the Netherlands.
FAU - Rovina, Nikoletta
AU  - Rovina N
AD  - 1(st) Department of Pulmonary Medicine and Intensive Care Unit, National and 
      Kapodistrian University of Athens, Medical School, 115 27 Athens, Greece.
FAU - Akinosoglou, Karolina
AU  - Akinosoglou K
AD  - Department of Internal Medicine, University of Patras, Medical School, 265 04 
      Rion, Greece.
FAU - Antoniadou, Anastasia
AU  - Antoniadou A
AD  - 4(th) Department of Internal Medicine, National and Kapodistrian University of 
      Athens, Medical School, 124 62 Athens, Greece.
FAU - Antonakos, Nikolaos
AU  - Antonakos N
AD  - 4(th) Department of Internal Medicine, National and Kapodistrian University of 
      Athens, Medical School, 124 62 Athens, Greece.
FAU - Damoraki, Georgia
AU  - Damoraki G
AD  - 4(th) Department of Internal Medicine, National and Kapodistrian University of 
      Athens, Medical School, 124 62 Athens, Greece.
FAU - Gkavogianni, Theologia
AU  - Gkavogianni T
AD  - 4(th) Department of Internal Medicine, National and Kapodistrian University of 
      Athens, Medical School, 124 62 Athens, Greece.
FAU - Adami, Maria-Evangelia
AU  - Adami ME
AD  - 4(th) Department of Internal Medicine, National and Kapodistrian University of 
      Athens, Medical School, 124 62 Athens, Greece.
FAU - Katsaounou, Paraskevi
AU  - Katsaounou P
AD  - 1(st) Department of Critical Care Medicine, National and Kapodistrian University 
      of Athens, 106 76 Athens, Medical School, Greece.
FAU - Ntaganou, Maria
AU  - Ntaganou M
AD  - 1(st) Department of Pulmonary Medicine and Intensive Care Unit, National and 
      Kapodistrian University of Athens, Medical School, 115 27 Athens, Greece.
FAU - Kyriakopoulou, Magdalini
AU  - Kyriakopoulou M
AD  - 1(st) Department of Pulmonary Medicine and Intensive Care Unit, National and 
      Kapodistrian University of Athens, Medical School, 115 27 Athens, Greece.
FAU - Dimopoulos, George
AU  - Dimopoulos G
AD  - 2(nd) Department of Critical Care Medicine, National and Kapodistrian University 
      of Athens, Medical School, 124 62 Athens, Greece.
FAU - Koutsodimitropoulos, Ioannis
AU  - Koutsodimitropoulos I
AD  - Internsive Care Unit, General Hospital of Elefsis Latseion, 196 00 Elefsis, 
      Greece.
FAU - Velissaris, Dimitrios
AU  - Velissaris D
AD  - Department of Internal Medicine, University of Patras, Medical School, 265 04 
      Rion, Greece.
FAU - Koufargyris, Panagiotis
AU  - Koufargyris P
AD  - 4(th) Department of Internal Medicine, National and Kapodistrian University of 
      Athens, Medical School, 124 62 Athens, Greece.
FAU - Karageorgos, Athanassios
AU  - Karageorgos A
AD  - 4(th) Department of Internal Medicine, National and Kapodistrian University of 
      Athens, Medical School, 124 62 Athens, Greece.
FAU - Katrini, Konstantina
AU  - Katrini K
AD  - 4(th) Department of Internal Medicine, National and Kapodistrian University of 
      Athens, Medical School, 124 62 Athens, Greece.
FAU - Lekakis, Vasileios
AU  - Lekakis V
AD  - 4(th) Department of Internal Medicine, National and Kapodistrian University of 
      Athens, Medical School, 124 62 Athens, Greece.
FAU - Lupse, Mihaela
AU  - Lupse M
AD  - Department of Infectious Diseases, University of Medicine and Pharmacy, 
      Cluj-Napoca, Romania.
FAU - Kotsaki, Antigone
AU  - Kotsaki A
AD  - 4(th) Department of Internal Medicine, National and Kapodistrian University of 
      Athens, Medical School, 124 62 Athens, Greece.
FAU - Renieris, George
AU  - Renieris G
AD  - 4(th) Department of Internal Medicine, National and Kapodistrian University of 
      Athens, Medical School, 124 62 Athens, Greece.
FAU - Theodoulou, Danai
AU  - Theodoulou D
AD  - 1(st) Department of Pulmonary Medicine and Intensive Care Unit, National and 
      Kapodistrian University of Athens, Medical School, 115 27 Athens, Greece.
FAU - Panou, Vassiliki
AU  - Panou V
AD  - 1(st) Department of Pulmonary Medicine and Intensive Care Unit, National and 
      Kapodistrian University of Athens, Medical School, 115 27 Athens, Greece.
FAU - Koukaki, Evangelia
AU  - Koukaki E
AD  - 1(st) Department of Pulmonary Medicine and Intensive Care Unit, National and 
      Kapodistrian University of Athens, Medical School, 115 27 Athens, Greece.
FAU - Koulouris, Nikolaos
AU  - Koulouris N
AD  - 1(st) Department of Pulmonary Medicine and Intensive Care Unit, National and 
      Kapodistrian University of Athens, Medical School, 115 27 Athens, Greece.
FAU - Gogos, Charalambos
AU  - Gogos C
AD  - Department of Internal Medicine, University of Patras, Medical School, 265 04 
      Rion, Greece.
FAU - Koutsoukou, Antonia
AU  - Koutsoukou A
AD  - 1(st) Department of Pulmonary Medicine and Intensive Care Unit, National and 
      Kapodistrian University of Athens, Medical School, 115 27 Athens, Greece.
LA  - eng
PT  - Journal Article
DEP - 20200421
PL  - United States
TA  - Cell Host Microbe
JT  - Cell host & microbe
JID - 101302316
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Interleukin-6)
RN  - I031V2H011 (tocilizumab)
SB  - IM
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/administration & dosage
MH  - COVID-19
MH  - Coronavirus Infections/*immunology/*pathology
MH  - Female
MH  - HLA-DR Antigens/immunology
MH  - Humans
MH  - Inflammation/pathology
MH  - Interleukin-6/immunology
MH  - Killer Cells, Natural/pathology
MH  - Lymphopenia/pathology
MH  - Macrophage Activation
MH  - Male
MH  - Monocytes/pathology
MH  - Pandemics
MH  - Pneumonia, Viral/*immunology/*pathology
MH  - Respiratory Insufficiency/*immunology
PMC - PMC7172841
OTO - NOTNLM
OT  - COVID-19
OT  - HLA-DR
OT  - SARS-CoV-2
OT  - dysregulation
OT  - ferritin
OT  - interleukin-6
OT  - lymphopenia
OT  - macrophage activation
OT  - monocytes
OT  - respiratory failure
COIS- Declaration of Interests E.J.G.-B. has received honoraria from AbbVie USA, Abbott 
      CH, InflaRx GmbH, MSD Greece, XBiotech Inc. and Angelini Italy; independent 
      educational grants from AbbVie, Abbott, Astellas Pharma Europe, AxisShield, 
      bioMerieux Inc, InflaRx GmbH, and XBiotech Inc; and funding from the FrameWork 7 
      program HemoSpec (granted to the National and Kapodistrian University of Athens), 
      the Horizon2020 Marie-Curie Project European Sepsis Academy (granted to the 
      National and Kapodistrian University of Athens), and the Horizon 2020 European 
      Grant ImmunoSep (granted to the Hellenic Institute for the Study of Sepsis). A.A. 
      has received honoraria and independent educational grants from Gilead, Pfizer, 
      MSD, ViiV, Astellas, and Biotest.
EDAT- 2020/04/23 06:00
MHDA- 2020/06/20 06:00
PMCR- 2020/04/21
CRDT- 2020/04/23 06:00
PHST- 2020/03/19 00:00 [received]
PHST- 2020/04/03 00:00 [revised]
PHST- 2020/04/09 00:00 [accepted]
PHST- 2020/04/23 06:00 [pubmed]
PHST- 2020/06/20 06:00 [medline]
PHST- 2020/04/23 06:00 [entrez]
PHST- 2020/04/21 00:00 [pmc-release]
AID - S1931-3128(20)30236-5 [pii]
AID - 10.1016/j.chom.2020.04.009 [doi]
PST - ppublish
SO  - Cell Host Microbe. 2020 Jun 10;27(6):992-1000.e3. doi: 
      10.1016/j.chom.2020.04.009. Epub 2020 Apr 21.