The Systemic Immune Response in COVID-19 Is Associated with a Shift to Formyl-Peptide Unresponsive Eosinophils

A malfunction of the innate immune response in COVID-19 is associated with eosinopenia, particularly in more severe cases. This study tested the hypothesis that this eosinopenia is COVID-19 specific and is associated with systemic activation of eosinophils. Blood of 15 healthy controls and 75 adult...

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Main Authors: Leo Koenderman, Maarten J. Siemers, Corneli van Aalst, Suzanne H. Bongers, Roy Spijkerman, Bas J. J. Bindels, Giulio Giustarini, Harriët M. R. van Goor, Karin A. H. Kaasjager, Nienke Vrisekoop
Format: Article
Language:English
Published: MDPI AG 2021-05-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/10/5/1109
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author Leo Koenderman
Maarten J. Siemers
Corneli van Aalst
Suzanne H. Bongers
Roy Spijkerman
Bas J. J. Bindels
Giulio Giustarini
Harriët M. R. van Goor
Karin A. H. Kaasjager
Nienke Vrisekoop
author_facet Leo Koenderman
Maarten J. Siemers
Corneli van Aalst
Suzanne H. Bongers
Roy Spijkerman
Bas J. J. Bindels
Giulio Giustarini
Harriët M. R. van Goor
Karin A. H. Kaasjager
Nienke Vrisekoop
author_sort Leo Koenderman
collection DOAJ
description A malfunction of the innate immune response in COVID-19 is associated with eosinopenia, particularly in more severe cases. This study tested the hypothesis that this eosinopenia is COVID-19 specific and is associated with systemic activation of eosinophils. Blood of 15 healthy controls and 75 adult patients with suspected COVID-19 at the ER were included before PCR testing and analyzed by point-of-care automated flow cytometry (CD10, CD11b, CD16, and CD62L) in the absence or presence of a formyl peptide (fNLF). Forty-five SARS-CoV-2 PCR positive patients were grouped based on disease severity. PCR negative patients with proven bacterial (<i>n</i> = 20) or other viral (<i>n</i> = 10) infections were used as disease controls. Eosinophils were identified with the use of the FlowSOM algorithm. Low blood eosinophil numbers (<100 cells/μL; <i>p</i> < 0.005) were found both in patients with COVID-19 and with other infectious diseases, albeit less pronounced. Two discrete eosinophil populations were identified in healthy controls both before and after activation with fNLF based on the expression of CD11b. Before activation, the CD11b<sup>bright</sup> population consisted of 5.4% (CI<sub>95%</sub> = 3.8, 13.4) of total eosinophils. After activation, this population of CD11b<sup>bright</sup> cells comprised nearly half the population (42.21%, CI<sub>95%</sub> = 35.9, 54.1). Eosinophils in COVID-19 had a similar percentage of CD11b<sup>bright</sup> cells before activation (7.6%, CI<sub>95%</sub> = 4.5, 13.6), but were clearly refractory to activation with fNLF as a much lower percentage of cells end up in the CD11b<sup>bright</sup> fraction after activation (23.7%, CI<sub>95%</sub> = 18.5, 27.6; <i>p</i> < 0.001). Low eosinophil numbers in COVID-19 are associated with refractoriness in responsiveness to fNLF. This might be caused by migration of fully functional cells to the tissue.
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spelling doaj.art-17bbca8f8bc14ac79183481f847dfc212023-11-21T18:24:05ZengMDPI AGCells2073-44092021-05-01105110910.3390/cells10051109The Systemic Immune Response in COVID-19 Is Associated with a Shift to Formyl-Peptide Unresponsive EosinophilsLeo Koenderman0Maarten J. Siemers1Corneli van Aalst2Suzanne H. Bongers3Roy Spijkerman4Bas J. J. Bindels5Giulio Giustarini6Harriët M. R. van Goor7Karin A. H. Kaasjager8Nienke Vrisekoop9Department of Respiratory Medicine, University Medical Center Utrecht, 3584CX Utrecht, The NetherlandsDepartment of Respiratory Medicine, University Medical Center Utrecht, 3584CX Utrecht, The NetherlandsDepartment of Respiratory Medicine, University Medical Center Utrecht, 3584CX Utrecht, The NetherlandsCenter for Translational Immunology, University Medical Center Utrecht, 3584CX Utrecht, The NetherlandsDepartment of Respiratory Medicine, University Medical Center Utrecht, 3584CX Utrecht, The NetherlandsDepartment of Respiratory Medicine, University Medical Center Utrecht, 3584CX Utrecht, The NetherlandsDepartment of Respiratory Medicine, University Medical Center Utrecht, 3584CX Utrecht, The NetherlandsDepartment of Internal Medicine, University Medical Center Utrecht, 3584CX Utrecht, The NetherlandsDepartment of Internal Medicine, University Medical Center Utrecht, 3584CX Utrecht, The NetherlandsDepartment of Respiratory Medicine, University Medical Center Utrecht, 3584CX Utrecht, The NetherlandsA malfunction of the innate immune response in COVID-19 is associated with eosinopenia, particularly in more severe cases. This study tested the hypothesis that this eosinopenia is COVID-19 specific and is associated with systemic activation of eosinophils. Blood of 15 healthy controls and 75 adult patients with suspected COVID-19 at the ER were included before PCR testing and analyzed by point-of-care automated flow cytometry (CD10, CD11b, CD16, and CD62L) in the absence or presence of a formyl peptide (fNLF). Forty-five SARS-CoV-2 PCR positive patients were grouped based on disease severity. PCR negative patients with proven bacterial (<i>n</i> = 20) or other viral (<i>n</i> = 10) infections were used as disease controls. Eosinophils were identified with the use of the FlowSOM algorithm. Low blood eosinophil numbers (<100 cells/μL; <i>p</i> < 0.005) were found both in patients with COVID-19 and with other infectious diseases, albeit less pronounced. Two discrete eosinophil populations were identified in healthy controls both before and after activation with fNLF based on the expression of CD11b. Before activation, the CD11b<sup>bright</sup> population consisted of 5.4% (CI<sub>95%</sub> = 3.8, 13.4) of total eosinophils. After activation, this population of CD11b<sup>bright</sup> cells comprised nearly half the population (42.21%, CI<sub>95%</sub> = 35.9, 54.1). Eosinophils in COVID-19 had a similar percentage of CD11b<sup>bright</sup> cells before activation (7.6%, CI<sub>95%</sub> = 4.5, 13.6), but were clearly refractory to activation with fNLF as a much lower percentage of cells end up in the CD11b<sup>bright</sup> fraction after activation (23.7%, CI<sub>95%</sub> = 18.5, 27.6; <i>p</i> < 0.001). Low eosinophil numbers in COVID-19 are associated with refractoriness in responsiveness to fNLF. This might be caused by migration of fully functional cells to the tissue.https://www.mdpi.com/2073-4409/10/5/1109SARS-CoV-2COVID-19point-of-care flow cytometryeosinophilformyl peptideresponsiveness
spellingShingle Leo Koenderman
Maarten J. Siemers
Corneli van Aalst
Suzanne H. Bongers
Roy Spijkerman
Bas J. J. Bindels
Giulio Giustarini
Harriët M. R. van Goor
Karin A. H. Kaasjager
Nienke Vrisekoop
The Systemic Immune Response in COVID-19 Is Associated with a Shift to Formyl-Peptide Unresponsive Eosinophils
Cells
SARS-CoV-2
COVID-19
point-of-care flow cytometry
eosinophil
formyl peptide
responsiveness
title The Systemic Immune Response in COVID-19 Is Associated with a Shift to Formyl-Peptide Unresponsive Eosinophils
title_full The Systemic Immune Response in COVID-19 Is Associated with a Shift to Formyl-Peptide Unresponsive Eosinophils
title_fullStr The Systemic Immune Response in COVID-19 Is Associated with a Shift to Formyl-Peptide Unresponsive Eosinophils
title_full_unstemmed The Systemic Immune Response in COVID-19 Is Associated with a Shift to Formyl-Peptide Unresponsive Eosinophils
title_short The Systemic Immune Response in COVID-19 Is Associated with a Shift to Formyl-Peptide Unresponsive Eosinophils
title_sort systemic immune response in covid 19 is associated with a shift to formyl peptide unresponsive eosinophils
topic SARS-CoV-2
COVID-19
point-of-care flow cytometry
eosinophil
formyl peptide
responsiveness
url https://www.mdpi.com/2073-4409/10/5/1109
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