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1072. SARS-CoV-2 Antibody Levels Associate with Neutrophil Activation

BACKGROUND: COVID-19 disease severity and outcomes have been linked to high antibody titers and a dysregulated neutrophil immune response. Here we query associations and connections between the endogenous SARS-CoV-2 antibody response and neutrophil activation in COVID-19. METHODS: Baseline serum or...

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Autores principales: Warner, Seth, Miao, Rui, Ramos-Benitez, Marcos J, Tian, Xin, Reger, Robert, Burbelo, Peter D, Kanthi, Yogendra, Cohen, Jeffrey I, Suffredini, Anthony F, Nathan, Steven D, Childs, Richard W, Chertow, Daniel S, Strich, Jeffrey R
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9752321/
http://dx.doi.org/10.1093/ofid/ofac492.913
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author Warner, Seth
Miao, Rui
Ramos-Benitez, Marcos J
Tian, Xin
Reger, Robert
Burbelo, Peter D
Kanthi, Yogendra
Kanthi, Yogendra
Cohen, Jeffrey I
Suffredini, Anthony F
Nathan, Steven D
Childs, Richard W
Childs, Richard W
Childs, Richard W
Chertow, Daniel S
Strich, Jeffrey R
author_facet Warner, Seth
Miao, Rui
Ramos-Benitez, Marcos J
Tian, Xin
Reger, Robert
Burbelo, Peter D
Kanthi, Yogendra
Kanthi, Yogendra
Cohen, Jeffrey I
Suffredini, Anthony F
Nathan, Steven D
Childs, Richard W
Childs, Richard W
Childs, Richard W
Chertow, Daniel S
Strich, Jeffrey R
author_sort Warner, Seth
collection PubMed
description BACKGROUND: COVID-19 disease severity and outcomes have been linked to high antibody titers and a dysregulated neutrophil immune response. Here we query associations and connections between the endogenous SARS-CoV-2 antibody response and neutrophil activation in COVID-19. METHODS: Baseline serum or plasma samples from 57 patients hospitalized on oxygen with COVID-19 were used to perform; 1) quantitative measurements of SARS-CoV-2 specific antibodies using a luciferase-based immunoprecipitation system assay, 2) quantitative measurements of neutrophil specific biomarkers using Luminex technology, and 3) neutrophil extracellular traps (NETs) as measured by myeloperoxidase-DNA (MPO-DNA) complexes by ELISA. Absolute neutrophil count (ANC) and immature granulocyte count (IGC) were measured from complete blood counts (CBC). Antibody levels were compared by disease severity using Wilcoxon rank-sum test and correlations were generated between antibody levels and neutrophil activation markers using Spearman’s correlation (SC). RESULTS: In a cohort of hospitalized patients, severe/critical COVID-19 was associated with higher levels of nucleocapsid-IgA (p=0.011) as well as spike-IgG (p= 0.0007) compared to moderate disease, while spike-IgA and nucleocapsid-IgG showed similar associations, trending towards significance (Figure 1A). Levels of IgG-spike and IgG-nucleocapsid both had significant correlations with the ANC (SC 0.33, p = 0.029; SC 0.38 p = 0.012). All four antibody titers showed strong correlations with IGC, lactoferrin and lipocalin-2, evidence of emergency granulopoiesis. Further, S100A9, a component calprotectin correlated with spike-IgG and nucleocapsid-IgA levels (SC 0.29, p = 0.030, SC 0.29 p = 0.029). Lastly, we found circulating NETs correlated with spike IgA levels (SC 0.38 p = 0.006), and its correlations with IgG-spike and IgA-nucleocapsid additionally approached significance with NETs levels as well (Figure 1B). Antibody Levels Correlate with Disease Severity and Neutrophil Activation Markers [Figure: see text] Figure 1: A) Levels of anti-Spike and anti-Nucleocapsid IgA and IgG levels measured in the serum of 57 unvaccinated hospitalized COVID-19 patients. Moderate illness represents ordinal scale 5 requiring low flow oxygen, while severe/critical patients represent ordinal scale 6 and 7, requiring high flow oxygen, non-invasive or mechanical ventilation, respectively. P values are compared by a Wilcoxon ranked sum test. B) Heatmap showing Spearman correlations between levels of anti-Spike and anti-Nucleocapsid IgA and IgG and markers of neutrophil activation. P values for individual correlations are represented in parentheses. MPO (myeloperoxidase), ANC (absolute neutrophil count), S100A9 (S100 calcium binding protein A9). CONCLUSION: Higher anti-spike and anti-nucleocapsid IgG and IgA levels associate with more severe COVID-19 illness. Further, endogenous SARS-CoV-2 specific antibody levels associate with markers of emergency granulopoiesis and neutrophil activation. Inhibiting antibody mediated neutrophil activation may improve outcomes in COVID-19. DISCLOSURES: All Authors: No reported disclosures.
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spelling pubmed-97523212022-12-16 1072. SARS-CoV-2 Antibody Levels Associate with Neutrophil Activation Warner, Seth Miao, Rui Ramos-Benitez, Marcos J Tian, Xin Reger, Robert Burbelo, Peter D Kanthi, Yogendra Kanthi, Yogendra Cohen, Jeffrey I Suffredini, Anthony F Nathan, Steven D Childs, Richard W Childs, Richard W Childs, Richard W Chertow, Daniel S Strich, Jeffrey R Open Forum Infect Dis Abstracts BACKGROUND: COVID-19 disease severity and outcomes have been linked to high antibody titers and a dysregulated neutrophil immune response. Here we query associations and connections between the endogenous SARS-CoV-2 antibody response and neutrophil activation in COVID-19. METHODS: Baseline serum or plasma samples from 57 patients hospitalized on oxygen with COVID-19 were used to perform; 1) quantitative measurements of SARS-CoV-2 specific antibodies using a luciferase-based immunoprecipitation system assay, 2) quantitative measurements of neutrophil specific biomarkers using Luminex technology, and 3) neutrophil extracellular traps (NETs) as measured by myeloperoxidase-DNA (MPO-DNA) complexes by ELISA. Absolute neutrophil count (ANC) and immature granulocyte count (IGC) were measured from complete blood counts (CBC). Antibody levels were compared by disease severity using Wilcoxon rank-sum test and correlations were generated between antibody levels and neutrophil activation markers using Spearman’s correlation (SC). RESULTS: In a cohort of hospitalized patients, severe/critical COVID-19 was associated with higher levels of nucleocapsid-IgA (p=0.011) as well as spike-IgG (p= 0.0007) compared to moderate disease, while spike-IgA and nucleocapsid-IgG showed similar associations, trending towards significance (Figure 1A). Levels of IgG-spike and IgG-nucleocapsid both had significant correlations with the ANC (SC 0.33, p = 0.029; SC 0.38 p = 0.012). All four antibody titers showed strong correlations with IGC, lactoferrin and lipocalin-2, evidence of emergency granulopoiesis. Further, S100A9, a component calprotectin correlated with spike-IgG and nucleocapsid-IgA levels (SC 0.29, p = 0.030, SC 0.29 p = 0.029). Lastly, we found circulating NETs correlated with spike IgA levels (SC 0.38 p = 0.006), and its correlations with IgG-spike and IgA-nucleocapsid additionally approached significance with NETs levels as well (Figure 1B). Antibody Levels Correlate with Disease Severity and Neutrophil Activation Markers [Figure: see text] Figure 1: A) Levels of anti-Spike and anti-Nucleocapsid IgA and IgG levels measured in the serum of 57 unvaccinated hospitalized COVID-19 patients. Moderate illness represents ordinal scale 5 requiring low flow oxygen, while severe/critical patients represent ordinal scale 6 and 7, requiring high flow oxygen, non-invasive or mechanical ventilation, respectively. P values are compared by a Wilcoxon ranked sum test. B) Heatmap showing Spearman correlations between levels of anti-Spike and anti-Nucleocapsid IgA and IgG and markers of neutrophil activation. P values for individual correlations are represented in parentheses. MPO (myeloperoxidase), ANC (absolute neutrophil count), S100A9 (S100 calcium binding protein A9). CONCLUSION: Higher anti-spike and anti-nucleocapsid IgG and IgA levels associate with more severe COVID-19 illness. Further, endogenous SARS-CoV-2 specific antibody levels associate with markers of emergency granulopoiesis and neutrophil activation. Inhibiting antibody mediated neutrophil activation may improve outcomes in COVID-19. DISCLOSURES: All Authors: No reported disclosures. Oxford University Press 2022-12-15 /pmc/articles/PMC9752321/ http://dx.doi.org/10.1093/ofid/ofac492.913 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Abstracts
Warner, Seth
Miao, Rui
Ramos-Benitez, Marcos J
Tian, Xin
Reger, Robert
Burbelo, Peter D
Kanthi, Yogendra
Kanthi, Yogendra
Cohen, Jeffrey I
Suffredini, Anthony F
Nathan, Steven D
Childs, Richard W
Childs, Richard W
Childs, Richard W
Chertow, Daniel S
Strich, Jeffrey R
1072. SARS-CoV-2 Antibody Levels Associate with Neutrophil Activation
title 1072. SARS-CoV-2 Antibody Levels Associate with Neutrophil Activation
title_full 1072. SARS-CoV-2 Antibody Levels Associate with Neutrophil Activation
title_fullStr 1072. SARS-CoV-2 Antibody Levels Associate with Neutrophil Activation
title_full_unstemmed 1072. SARS-CoV-2 Antibody Levels Associate with Neutrophil Activation
title_short 1072. SARS-CoV-2 Antibody Levels Associate with Neutrophil Activation
title_sort 1072. sars-cov-2 antibody levels associate with neutrophil activation
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9752321/
http://dx.doi.org/10.1093/ofid/ofac492.913
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