PMID- 32925314
OWN - NLM
STAT- MEDLINE
DCOM- 20200924
LR  - 20221005
IS  - 1526-7598 (Electronic)
IS  - 0003-2999 (Print)
IS  - 0003-2999 (Linking)
VI  - 131
IP  - 4
DP  - 2020 Oct
TI  - Reduced Monocytic Human Leukocyte Antigen-DR Expression Indicates 
      Immunosuppression in Critically Ill COVID-19 Patients.
PG  - 993-999
LID - 10.1213/ANE.0000000000005044 [doi]
AB  - BACKGROUND: The cellular immune system is of pivotal importance with regard to 
      the response to severe infections. Monocytes/macrophages are considered key 
      immune cells in infections and downregulation of the surface expression of 
      monocytic human leukocyte antigen-DR (mHLA-DR) within the major 
      histocompatibility complex class II reflects a state of immunosuppression, also 
      referred to as injury-associated immunosuppression. As the role of 
      immunosuppression in coronavirus disease 2019 (COVID-19) is currently unclear, we 
      seek to explore the level of mHLA-DR expression in COVID-19 patients. METHODS: In 
      a preliminary prospective monocentric observational study, 16 COVID-19-positive 
      patients (75% male, median age: 68 [interquartile range 59-75]) requiring 
      hospitalization were included. The median Acute Physiology and Chronic Health 
      Evaluation-II (APACHE-II) score in 9 intensive care unit (ICU) patients with 
      acute respiratory failure was 30 (interquartile range 25-32). Standardized 
      quantitative assessment of HLA-DR on monocytes (cluster of differentiation 14+ 
      cells) was performed using calibrated flow cytometry at baseline (ICU/hospital 
      admission) and at days 3 and 5 after ICU admission. Baseline data were compared 
      to hospitalized noncritically ill COVID-19 patients. RESULTS: While normal 
      mHLA-DR expression was observed in all hospitalized noncritically ill patients (n 
      = 7), 89% (8 of 9) critically ill patients with COVID-19-induced acute 
      respiratory failure showed signs of downregulation of mHLA-DR at ICU admission. 
      mHLA-DR expression at admission was significantly lower in critically ill 
      patients (median, [quartiles]: 9280 antibodies/cell [6114, 16,567]) as compared 
      to the noncritically ill patients (30,900 antibodies/cell [26,777, 52,251]), with 
      a median difference of 21,508 antibodies/cell (95% confidence interval [CI], 
      14,118-42,971), P = .002. Reduced mHLA-DR expression was observed to persist 
      until day 5 after ICU admission. CONCLUSIONS: When compared to noncritically ill 
      hospitalized COVID-19 patients, ICU patients with severe COVID-19 disease showed 
      reduced mHLA-DR expression on circulating CD14+ monocytes at ICU admission, 
      indicating a dysfunctional immune response. This immunosuppressive (monocytic) 
      phenotype remained unchanged over the ensuing days after ICU admission. 
      Strategies aiming for immunomodulation in this population of critically ill 
      patients should be guided by an immune-monitoring program in an effort to 
      determine who might benefit best from a given immunological intervention.
FAU - Spinetti, Thibaud
AU  - Spinetti T
AD  - From the Department of Intensive Care Medicine, Inselspital, Bern University 
      Hospital, University of Bern.
FAU - Hirzel, Cedric
AU  - Hirzel C
AD  - Department of Infectious Diseases, Inselspital, Bern University Hospital, 
      University of Bern.
FAU - Fux, Michaela
AU  - Fux M
AD  - University Institute of Clinical Chemistry, Inselspital, University of Bern, 
      Bern, Switzerland.
FAU - Walti, Laura N
AU  - Walti LN
AD  - Department of Infectious Diseases, Inselspital, Bern University Hospital, 
      University of Bern.
FAU - Schober, Patrick
AU  - Schober P
AD  - Department of Anaesthesiology, Amsterdam University Medical Centres, Vrije 
      Universiteit Amsterdam, Amsterdam, the Netherlands.
FAU - Stueber, Frank
AU  - Stueber F
AD  - Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University 
      Hospital, University of Bern, Bern, Switzerland.
FAU - Luedi, Markus M
AU  - Luedi MM
AD  - Department of Anaesthesiology and Pain Medicine, Inselspital, Bern University 
      Hospital, University of Bern, Bern, Switzerland.
FAU - Schefold, Joerg C
AU  - Schefold JC
AD  - From the Department of Intensive Care Medicine, Inselspital, Bern University 
      Hospital, University of Bern.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Anesth Analg
JT  - Anesthesia and analgesia
JID - 1310650
RN  - 0 (Antibodies)
RN  - 0 (HLA-DR Antigens)
RN  - 0 (Lipopolysaccharide Receptors)
SB  - IM
CIN - Anesth Analg. 2020 Oct;131(4):989-992. PMID: 32925313
MH  - APACHE
MH  - Aged
MH  - Antibodies/analysis/immunology
MH  - COVID-19
MH  - Coronavirus Infections/*immunology/therapy
MH  - Critical Care
MH  - *Critical Illness
MH  - Down-Regulation/immunology
MH  - Female
MH  - HLA-DR Antigens/*biosynthesis/*immunology
MH  - Humans
MH  - Immune Tolerance/*immunology
MH  - Immunotherapy
MH  - Lipopolysaccharide Receptors/immunology
MH  - Male
MH  - Middle Aged
MH  - Monocytes/immunology
MH  - Pandemics
MH  - Pneumonia, Viral/*immunology/therapy
MH  - Prospective Studies
MH  - Respiratory Insufficiency/immunology/physiopathology
PMC - PMC7288784
COIS- Conflicts of Interest: See Disclosures at the end of the article.
EDAT- 2020/09/15 06:00
MHDA- 2020/09/25 06:00
PMCR- 2020/09/02
CRDT- 2020/09/14 15:43
PHST- 2020/09/14 15:43 [entrez]
PHST- 2020/09/15 06:00 [pubmed]
PHST- 2020/09/25 06:00 [medline]
PHST- 2020/09/02 00:00 [pmc-release]
AID - 00000539-202010000-00002 [pii]
AID - 10.1213/ANE.0000000000005044 [doi]
PST - ppublish
SO  - Anesth Analg. 2020 Oct;131(4):993-999. doi: 10.1213/ANE.0000000000005044.