FlowRepository

Repository ID:	FR-FCM-Z2MW	Experiment name:	Contagious Trial CyTOF	MIFlowCyt score:	79.66%
Primary researcher:	Pier Andree Penttila	PI/manager:	Pier Andree Penttila	Uploaded by:	Pier Andree Penttila
Experiment dates:	2020-03-27 - 2020-04-17	Dataset uploaded:	May 2020	Last updated:	Feb 2021
Keywords:	[Innate Immune Response] [cytokines] [Immunophenotyping] [monocytes] [bronchoalveolar lavage] [human neutrophils] [adaptive immunity] [myeloid dendritic cells] [T lymphocytes] [NK cells.] [COVID-19] [CyTOF; mass cytometry; flow cytometry] [scRNA seq] [antigen presentation] [Interferon-gamma] [IL 1B protein] [Interleukin-8] [Extracellular Traps]		Manuscripts:
Organizations:	KU Leuven, Leuven, Vlaams Brabant (Belgium)
Purpose:	Monocyte-driven atypical cytokine storm and aberrant neutrophil activation as key mediators of COVID-19 disease severity
Conclusion:	The host immune response in symptomatic COVID-19 patients seems ineffective in clearing SARS-CoV-2, yet excessive in causing local tissue damage and hypercytokinemia. To elucidate the immunopathology underlying COVID-19 severity, cytokine profiling was performed in mild-moderate and critically-ill COVID-19 patients. Hypercytokinemia in COVID-19 differed from the IFN-γ-driven cytokine storm in macrophage activation syndrome, but was increased in critical versus mild-moderate COVID-19. Prediction modelling of cytokine levels followed by deep-immune profiling showed that classical monocytes drive this hyper-inflammatory phenotype and that both a quantitative and qualitative reduction in T-lymphocytes correlate with disease severity, with CD8+ cells being disproportionately affected. Expression of antigen presentation and co-stimulatory molecules was reduced in critical disease, while also neutrophils contributed to disease severity and local tissue damage by amplifying hypercytokinemia and neutrophil extracellular trap formation. We suggest a monocyte-driven immunopathology, in which hyperactivated neutrophils and an ineffective adaptive immune system act as mediators of COVID-19 disease severity.
Comments:	None
Funding:	This work was funded by KU Leuven (internal fund and grant C14/17/084 and C16/17/010), VIB (Grand Challenge project), UZ Leuven (KOOR project), FWO grant I007418N, the Rega Foundation (research expert fellowship to G.M.) and ‘het Leuvens Kankerinstituut’. This project has also received funding within the Grand Challenges Program of VIB. This VIB Program received support from the Flemish Government under the Management Agreement 2017-2021 (VR 2016 2312 Doc.1521/4).
Quality control:	Healthy controls Reference control throughout study to evaluate batch effects during Helios runs Titration of antibodies Evaluation of cryopreservation effects on antigen expression

Experiment variables

Timepoints
· ICU	COVID_ICU_023_A_LiHep_00_1.fcs · COVID_ICU_025_A_LiHep_00_1.fcs · COVID_ICU_027_A_LiHep_00_1.fcs · COVID_ICU_029_A_LiHep_00_1.fcs · COVID_ICU_031_A_LiHep_02_1.fcs · COVID_ICU_036_A_LiHep_00_1.fcs · COVID_ICU_039_A_LiHep_00_1.fcs · COVID_ICU_043_A_LiHep_00_1.fcs · Covid_ICU_013_Admission_WB1_01_1.fcs · Covid_ICU_014_Admission_WB2_02_1.fcs · Covid_ICU_015_Admission_WB3_03_1.fcs · Covid_ICU_016_Admission_WB4_04_1.fcs · Covid_ICU_045_A_LiHep_00_1.fcs
· Ward	COVID_W_008_O_LiHep_00_1.fcs · COVID_W_009_O_LiHep_00_1.fcs · COVID_W_010_O_LiHep_00_1.fcs · COVID_W_016_O_LiHep_00_1.fcs · COVID_W_018_O_LiHep_00_1.fcs · COVID_W_019_O_LiHep_00_1.fcs · COVID_W_021_O_LiHep_00_1.fcs · COVID_W_024_O_LiHep_00_1.fcs · COVID_W_025_O_LiHep_00_1.fcs · COVID_W_026_O_LiHep_00_1.fcs · COVID_W_027_O_LiHep_00_1.fcs · COVID_W_028_O_LiHep_00_1.fcs · COVID_W_029_O_LiHep_00_1.fcs · COVID_W_030_O_LiHep_00_1.fcs · COVID_W_031_O_LiHep_00_1.fcs · COVID_W_033_O_LiHep_00_1.fcs · COVID_W_035_O_LiHep_01_1.fcs · COVID_W_036_O_LiHep_00_1.fcs · COVID_W_037_O_LiHep_00_1.fcs · Covid_W_006_O_LiHep_00_1.fcs · Covid_W_007_O_LiHep_00_1.fcs · Covid_W_011_O_00_1.fcs · Covid_W_012_0_00_1.fcs · Covid_W_014_O_02_1.fcs · Covid_W_015_O_00_1.fcs · Covid_W_017_O_00_1.fcs · Covid_W_040_O_LiHep_00_1.fcs · Covid_W_042_O_00_1.fcs · Covid_W_043_O_LiHep_00_1.fcs · Covid_W_046_O_LiHep_00_1.fcs · Covid_W_047_O_LiHep_00_1.fcs · Covid_W_048_O_LiHep_00_1.fcs · Covid_W_049_O_LiHep_00_1.fcs
· Healthy Controls	Covid_HC_001_01_1.fcs · Covid_HC_003_01_1.fcs · Covid_HC_004_01_1.fcs · Covid_HC_005_01_1.fcs · Covid_HC_006_00_1.fcs · Covid_HC_007_00_1.fcs · Covid_HC_008_00_1.fcs · Covid_HC_009_00_1.fcs

Sample Type
· Human whole blood	COVID_ICU_023_A_LiHep_00_1.fcs · COVID_ICU_025_A_LiHep_00_1.fcs · COVID_ICU_027_A_LiHep_00_1.fcs · COVID_ICU_029_A_LiHep_00_1.fcs · COVID_ICU_031_A_LiHep_02_1.fcs · COVID_ICU_036_A_LiHep_00_1.fcs · COVID_ICU_039_A_LiHep_00_1.fcs · COVID_ICU_043_A_LiHep_00_1.fcs · COVID_W_008_O_LiHep_00_1.fcs · COVID_W_009_O_LiHep_00_1.fcs · COVID_W_010_O_LiHep_00_1.fcs · COVID_W_016_O_LiHep_00_1.fcs · COVID_W_018_O_LiHep_00_1.fcs · COVID_W_019_O_LiHep_00_1.fcs · COVID_W_021_O_LiHep_00_1.fcs · COVID_W_024_O_LiHep_00_1.fcs · COVID_W_025_O_LiHep_00_1.fcs · COVID_W_026_O_LiHep_00_1.fcs · COVID_W_027_O_LiHep_00_1.fcs · COVID_W_028_O_LiHep_00_1.fcs · COVID_W_029_O_LiHep_00_1.fcs · COVID_W_030_O_LiHep_00_1.fcs · COVID_W_031_O_LiHep_00_1.fcs · COVID_W_033_O_LiHep_00_1.fcs · COVID_W_035_O_LiHep_01_1.fcs · COVID_W_036_O_LiHep_00_1.fcs · COVID_W_037_O_LiHep_00_1.fcs · Covid_HC_001_01_1.fcs · Covid_HC_003_01_1.fcs · Covid_HC_004_01_1.fcs · Covid_HC_005_01_1.fcs · Covid_HC_006_00_1.fcs · Covid_HC_007_00_1.fcs · Covid_HC_008_00_1.fcs · Covid_HC_009_00_1.fcs · Covid_ICU_013_Admission_WB1_01_1.fcs · Covid_ICU_014_Admission_WB2_02_1.fcs · Covid_ICU_015_Admission_WB3_03_1.fcs · Covid_ICU_016_Admission_WB4_04_1.fcs · Covid_ICU_045_A_LiHep_00_1.fcs · Covid_W_006_O_LiHep_00_1.fcs · Covid_W_007_O_LiHep_00_1.fcs · Covid_W_011_O_00_1.fcs · Covid_W_012_0_00_1.fcs · Covid_W_014_O_02_1.fcs · Covid_W_015_O_00_1.fcs · Covid_W_017_O_00_1.fcs · Covid_W_040_O_LiHep_00_1.fcs · Covid_W_042_O_00_1.fcs · Covid_W_043_O_LiHep_00_1.fcs · Covid_W_046_O_LiHep_00_1.fcs · Covid_W_047_O_LiHep_00_1.fcs · Covid_W_048_O_LiHep_00_1.fcs · Covid_W_049_O_LiHep_00_1.fcs

Individuals
· ICU	COVID_ICU_023_A_LiHep_00_1.fcs · COVID_ICU_025_A_LiHep_00_1.fcs · COVID_ICU_027_A_LiHep_00_1.fcs · COVID_ICU_029_A_LiHep_00_1.fcs · COVID_ICU_031_A_LiHep_02_1.fcs · COVID_ICU_036_A_LiHep_00_1.fcs · COVID_ICU_039_A_LiHep_00_1.fcs · COVID_ICU_043_A_LiHep_00_1.fcs · Covid_ICU_013_Admission_WB1_01_1.fcs · Covid_ICU_014_Admission_WB2_02_1.fcs · Covid_ICU_015_Admission_WB3_03_1.fcs · Covid_ICU_016_Admission_WB4_04_1.fcs · Covid_ICU_045_A_LiHep_00_1.fcs
· Healthy Controls	Covid_HC_001_01_1.fcs · Covid_HC_003_01_1.fcs · Covid_HC_004_01_1.fcs · Covid_HC_005_01_1.fcs · Covid_HC_006_00_1.fcs · Covid_HC_007_00_1.fcs · Covid_HC_008_00_1.fcs · Covid_HC_009_00_1.fcs
· Ward	COVID_W_008_O_LiHep_00_1.fcs · COVID_W_009_O_LiHep_00_1.fcs · COVID_W_010_O_LiHep_00_1.fcs · COVID_W_016_O_LiHep_00_1.fcs · COVID_W_018_O_LiHep_00_1.fcs · COVID_W_019_O_LiHep_00_1.fcs · COVID_W_021_O_LiHep_00_1.fcs · COVID_W_024_O_LiHep_00_1.fcs · COVID_W_025_O_LiHep_00_1.fcs · COVID_W_026_O_LiHep_00_1.fcs · COVID_W_027_O_LiHep_00_1.fcs · COVID_W_028_O_LiHep_00_1.fcs · COVID_W_029_O_LiHep_00_1.fcs · COVID_W_030_O_LiHep_00_1.fcs · COVID_W_031_O_LiHep_00_1.fcs · COVID_W_033_O_LiHep_00_1.fcs · COVID_W_035_O_LiHep_01_1.fcs · COVID_W_036_O_LiHep_00_1.fcs · COVID_W_037_O_LiHep_00_1.fcs · Covid_W_006_O_LiHep_00_1.fcs · Covid_W_007_O_LiHep_00_1.fcs · Covid_W_011_O_00_1.fcs · Covid_W_012_0_00_1.fcs · Covid_W_014_O_02_1.fcs · Covid_W_015_O_00_1.fcs · Covid_W_017_O_00_1.fcs · Covid_W_040_O_LiHep_00_1.fcs · Covid_W_042_O_00_1.fcs · Covid_W_043_O_LiHep_00_1.fcs · Covid_W_046_O_LiHep_00_1.fcs · Covid_W_047_O_LiHep_00_1.fcs · Covid_W_048_O_LiHep_00_1.fcs · Covid_W_049_O_LiHep_00_1.fcs

Conditions
· Fresh processed	COVID_ICU_023_A_LiHep_00_1.fcs · COVID_ICU_025_A_LiHep_00_1.fcs · COVID_ICU_027_A_LiHep_00_1.fcs · COVID_ICU_029_A_LiHep_00_1.fcs · COVID_ICU_031_A_LiHep_02_1.fcs · COVID_ICU_036_A_LiHep_00_1.fcs · COVID_ICU_039_A_LiHep_00_1.fcs · COVID_ICU_043_A_LiHep_00_1.fcs · COVID_W_008_O_LiHep_00_1.fcs · COVID_W_009_O_LiHep_00_1.fcs · COVID_W_010_O_LiHep_00_1.fcs · COVID_W_016_O_LiHep_00_1.fcs · COVID_W_018_O_LiHep_00_1.fcs · COVID_W_019_O_LiHep_00_1.fcs · COVID_W_021_O_LiHep_00_1.fcs · COVID_W_024_O_LiHep_00_1.fcs · COVID_W_025_O_LiHep_00_1.fcs · COVID_W_026_O_LiHep_00_1.fcs · COVID_W_027_O_LiHep_00_1.fcs · COVID_W_028_O_LiHep_00_1.fcs · COVID_W_029_O_LiHep_00_1.fcs · COVID_W_030_O_LiHep_00_1.fcs · COVID_W_031_O_LiHep_00_1.fcs · COVID_W_033_O_LiHep_00_1.fcs · COVID_W_035_O_LiHep_01_1.fcs · COVID_W_036_O_LiHep_00_1.fcs · COVID_W_037_O_LiHep_00_1.fcs · Covid_HC_001_01_1.fcs · Covid_HC_003_01_1.fcs · Covid_HC_004_01_1.fcs · Covid_ICU_013_Admission_WB1_01_1.fcs · Covid_ICU_014_Admission_WB2_02_1.fcs · Covid_ICU_015_Admission_WB3_03_1.fcs · Covid_ICU_016_Admission_WB4_04_1.fcs · Covid_W_006_O_LiHep_00_1.fcs · Covid_W_007_O_LiHep_00_1.fcs · Covid_W_011_O_00_1.fcs · Covid_W_012_0_00_1.fcs · Covid_W_014_O_02_1.fcs · Covid_W_015_O_00_1.fcs · Covid_W_017_O_00_1.fcs · Covid_W_042_O_00_1.fcs · Covid_W_043_O_LiHep_00_1.fcs · Covid_W_046_O_LiHep_00_1.fcs · Covid_W_047_O_LiHep_00_1.fcs
· Fresh processed then cryopreserved	Covid_HC_005_01_1.fcs · Covid_HC_006_00_1.fcs · Covid_HC_007_00_1.fcs · Covid_HC_008_00_1.fcs · Covid_HC_009_00_1.fcs · Covid_ICU_045_A_LiHep_00_1.fcs · Covid_W_040_O_LiHep_00_1.fcs · Covid_W_048_O_LiHep_00_1.fcs · Covid_W_049_O_LiHep_00_1.fcs