{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T16:46:32Z","timestamp":1768495592160,"version":"3.49.0"},"posted":{"date-parts":[[2021,10,5]]},"group-title":"Immunology","reference-count":87,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2021,10,5]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>\n                  Multiple studies have identified an association between neutrophils and COVID-19 disease severity; however, the mechanistic basis of this association remains incompletely understood. Here we collected 781 longitudinal blood samples from 306 hospitalized COVID-19\n                  <jats:sup>+<\/jats:sup>\n                  patients, 78 COVID-19\n                  <jats:sup>\u2212<\/jats:sup>\n                  acute respiratory distress syndrome patients, and 8 healthy controls, and performed bulk RNA-sequencing of enriched neutrophils, plasma proteomics, cfDNA measurements and high throughput antibody profiling assays to investigate the relationship between neutrophil states and disease severity or death. We identified dynamic switches between six distinct neutrophil subtypes using non-negative matrix factorization (NMF) clustering. At days 3 and 7 post-hospitalization, patients with severe disease had an enrichment of a granulocytic myeloid derived suppressor cell-like state gene expression signature, while non-severe patients with resolved disease were enriched for a progenitor-like immature neutrophil state signature. Severe disease was associated with gene sets related to neutrophil degranulation, neutrophil extracellular trap (NET) signatures, distinct metabolic signatures, and enhanced neutrophil activation and generation of reactive oxygen species (ROS). We found that the majority of patients had a transient interferon-stimulated gene signature upon presentation to the emergency department (ED) defined here as Day 0, regardless of disease severity, which persisted only in patients who subsequently died. Humoral responses were identified as potential drivers of neutrophil effector functions, as enhanced antibody-dependent neutrophil phagocytosis and reduced NETosis was associated with elevated SARS-CoV-2-specific IgG1-to-IgA1 ratios in plasma of severe patients who survived.\n                  <jats:italic>In vitro<\/jats:italic>\n                  experiments confirmed that while patient-derived IgG antibodies mostly drove neutrophil phagocytosis and ROS production in healthy donor neutrophils, patient-derived IgA antibodies induced a predominant NETosis response. Overall, our study demonstrates neutrophil dysregulation in severe COVID-19 and a potential role for IgA-dominant responses in driving neutrophil effector functions in severe disease and mortality.\n                <\/jats:p>","DOI":"10.1101\/2021.10.04.463121","type":"posted-content","created":{"date-parts":[[2021,10,5]],"date-time":"2021-10-05T22:07:05Z","timestamp":1633471625000},"source":"Crossref","is-referenced-by-count":2,"title":["Longitudinal characterization of circulating neutrophils uncovers distinct phenotypes associated with disease severity in hospitalized COVID-19 patients"],"prefix":"10.64898","author":[{"given":"Thomas J.","family":"LaSalle","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna L. K.","family":"Gonye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel S.","family":"Freeman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paulina","family":"Kaplonek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irena","family":"Gushterova","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyle R.","family":"Kays","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kasidet","family":"Manakongtreecheep","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Tantivit","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maricarmen","family":"Rojas-Lopez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian C.","family":"Russo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nihaarika","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Molly F.","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kendall M.","family":"Lavin-Parsons","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brendan M.","family":"Lilly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brenna N.","family":"Mckaig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole C.","family":"Charland","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hargun K.","family":"Khanna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carl L.","family":"Lodenstein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justin D.","family":"Margolin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily M.","family":"Blaum","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola B.","family":"Lirofonis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abraham","family":"Sonny","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roby P.","family":"Bhattacharyya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Blair Alden","family":"Parry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcia B.","family":"Goldberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Galit","family":"Alter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael R.","family":"Filbin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra Chloe","family":"Villani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nir","family":"Hacohen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moshe","family":"Sade-Feldman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2021100705200543000_2021.10.04.463121v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2951-z"},{"key":"2021100705200543000_2021.10.04.463121v1.2","unstructured":"The Visual and Data Journalism Team. Covid map: Coronavirus cases, deaths, vaccinations by country. BBC (2021)."},{"key":"2021100705200543000_2021.10.04.463121v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.04.026"},{"key":"2021100705200543000_2021.10.04.463121v1.4","doi-asserted-by":"crossref","first-page":"ofab019","DOI":"10.1093\/ofid\/ofab019","article-title":"Dysregulated Host Response in Severe Acute Respiratory Syndrome Coronavirus 2-Induced Critical Illness","volume":"8","year":"2021","journal-title":"Open Forum Infect Dis"},{"key":"2021100705200543000_2021.10.04.463121v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2588-y"},{"key":"2021100705200543000_2021.10.04.463121v1.6","doi-asserted-by":"crossref","unstructured":"Zhang, Q. et al. Inflammation and Antiviral Immune Response Associated With Severe Progr ession of COVID-19. Frontiers in Immunology vol. 12 (2021).","DOI":"10.3389\/fimmu.2021.631226"},{"key":"2021100705200543000_2021.10.04.463121v1.7","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1038\/s41467-021-21702-6","article-title":"Deciphering the state of immune silence in fatal COVID-19 patients","volume":"12","year":"2021","journal-title":"Nat. Commun"},{"key":"2021100705200543000_2021.10.04.463121v1.8","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1038\/s41586-021-03234-7","article-title":"Global absence and targeting of protective immune states in severe COVID-19","volume":"591","year":"2021","journal-title":"Nature"},{"key":"2021100705200543000_2021.10.04.463121v1.9","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1016\/j.cell.2020.10.052","article-title":"Compromised Humoral Functional Evolution Tracks with SARS-CoV-2 Mortality","volume":"183","year":"2020","journal-title":"Cell"},{"key":"2021100705200543000_2021.10.04.463121v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-020-00455-9"},{"key":"2021100705200543000_2021.10.04.463121v1.11","doi-asserted-by":"crossref","first-page":"1419","DOI":"10.1016\/j.cell.2020.08.001","article-title":"Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment","volume":"182","year":"2020","journal-title":"Cell"},{"key":"2021100705200543000_2021.10.04.463121v1.12","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-020-00823-5"},{"key":"2021100705200543000_2021.10.04.463121v1.13","doi-asserted-by":"crossref","first-page":"655934","DOI":"10.3389\/fimmu.2021.655934","article-title":"T cell activation, highly armed cytotoxic cells and a shift in monocytes CD300 receptors expression is characteristic of patients with severe COVID-19","volume":"12","year":"2021","journal-title":"Front. Immunol"},{"key":"2021100705200543000_2021.10.04.463121v1.14","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2020003568"},{"key":"2021100705200543000_2021.10.04.463121v1.15","doi-asserted-by":"publisher","DOI":"10.1101\/2020.12.18.423363"},{"key":"2021100705200543000_2021.10.04.463121v1.16","doi-asserted-by":"crossref","unstructured":"Uribe-Querol, E. & Rosales, C. Phagocytosis: Our Current Understanding of a Universal Biological Process. Front. Immunol. 11, (2020).","DOI":"10.3389\/fimmu.2020.01066"},{"key":"2021100705200543000_2021.10.04.463121v1.17","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1159\/000494371","article-title":"Primary Human Neutrophils Exhibit a Unique HIV-Directed Antibody-Dependent Phagocytosis Profile","volume":"11","year":"2019","journal-title":"Journal of Innate Immunity"},{"key":"2021100705200543000_2021.10.04.463121v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2018.03.007"},{"key":"2021100705200543000_2021.10.04.463121v1.19","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092385"},{"key":"2021100705200543000_2021.10.04.463121v1.20","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.59.2.229"},{"key":"2021100705200543000_2021.10.04.463121v1.21","doi-asserted-by":"publisher","DOI":"10.1101\/2021.01.04.424830"},{"key":"2021100705200543000_2021.10.04.463121v1.22","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00704"},{"key":"2021100705200543000_2021.10.04.463121v1.23","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09160-7"},{"key":"2021100705200543000_2021.10.04.463121v1.24","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1182\/blood.2020007008","article-title":"Neutrophil extracellular traps contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome","volume":"136","year":"2020","journal-title":"Blood"},{"key":"2021100705200543000_2021.10.04.463121v1.25","doi-asserted-by":"publisher","DOI":"10.1001\/jamacardio.2020.7308"},{"key":"2021100705200543000_2021.10.04.463121v1.26","doi-asserted-by":"crossref","unstructured":"Filbin, M. R. et al. Longitudinal proteomic analysis of plasma from patients with severe COVID-19 reveal patient survival-associated signatures, tissue-specific cell death, and cell-cell interactions. Cell Reports Medicine 100287 (2021).","DOI":"10.1016\/j.xcrm.2021.100287"},{"key":"2021100705200543000_2021.10.04.463121v1.27","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2012.09.007"},{"key":"2021100705200543000_2021.10.04.463121v1.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2017.01.010"},{"key":"2021100705200543000_2021.10.04.463121v1.29","doi-asserted-by":"crossref","unstructured":"Kaplonek, P. et al. Early cross-coronavirus reactive signatures of humoral immunity against COVID-19. Sci. Immunol. https:\/\/www.science.org\/doi\/10.1126\/sciimmunol.abj2901. (2021).","DOI":"10.1101\/2021.05.11.443609"},{"key":"2021100705200543000_2021.10.04.463121v1.30","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btab135"},{"key":"2021100705200543000_2021.10.04.463121v1.31","doi-asserted-by":"crossref","first-page":"106017","DOI":"10.1016\/j.ijantimicag.2020.106017","article-title":"Neutrophil-to-lymphocyte ratio and clinical outcome in COVID-19: a report from the Italian front line","volume":"56","year":"2020","journal-title":"Int. J. Antimicrob. Agents"},{"key":"2021100705200543000_2021.10.04.463121v1.32","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-020-02534-2"},{"key":"2021100705200543000_2021.10.04.463121v1.33","doi-asserted-by":"crossref","unstructured":"Long, L. et al. Short-term outcomes of COVID-19 and risk factors for progression. Eur. Respir. J. 55, (2020).","DOI":"10.1183\/13993003.00990-2020"},{"key":"2021100705200543000_2021.10.04.463121v1.34","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa248"},{"key":"2021100705200543000_2021.10.04.463121v1.35","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1016\/j.cmet.2021.01.002","article-title":"The Neutrophil-to-Lymphocyte Ratio Determines Clinical Efficacy of Corticosteroid Therapy in Patients with COVID-19","volume":"33","year":"2021","journal-title":"Cell Metab"},{"key":"2021100705200543000_2021.10.04.463121v1.36","doi-asserted-by":"crossref","first-page":"e6","DOI":"10.1016\/j.jinf.2020.04.002","article-title":"Neutrophil-to-lymphocyte ratio as an independent risk factor for mortality in hospitalized patients with COVID-19","volume":"81","year":"2020","journal-title":"J. Infect"},{"key":"2021100705200543000_2021.10.04.463121v1.37","doi-asserted-by":"crossref","unstructured":"Andargie, T. E. et al. Cell-free DNA maps COVID-19 tissue injury and risk of death and can cause tissue injury. JCI Insight 6, (2021).","DOI":"10.1172\/jci.insight.147610"},{"key":"2021100705200543000_2021.10.04.463121v1.38","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/s41587-019-0114-2","article-title":"Determining cell type abundance and expression from bulk tissues with digital cytometry","volume":"37","year":"2019","journal-title":"Nat. Biotechnol"},{"key":"2021100705200543000_2021.10.04.463121v1.39","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2002032"},{"key":"2021100705200543000_2021.10.04.463121v1.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.07.036"},{"key":"2021100705200543000_2021.10.04.463121v1.41","doi-asserted-by":"crossref","unstructured":"Injarabian, L. , Devin, A. , Ransac, S. & Marteyn, B. S. Neutrophil Metabolic Shift during their Lifecycle: Impact on their Survival and Activation. Int. J. Mol. Sci. 21, (2019).","DOI":"10.3390\/ijms21010287"},{"key":"2021100705200543000_2021.10.04.463121v1.42","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1016\/j.immuni.2019.03.009","article-title":"Single-Cell Transcriptomics of Human and Mouse Lung Cancers Reveals Conserved Myeloid Populations across Individuals and Species","volume":"50","year":"2019","journal-title":"Immunity"},{"key":"2021100705200543000_2021.10.04.463121v1.43","doi-asserted-by":"crossref","unstructured":"Reyes, M. et al. Plasma from patients with bacterial sepsis or severe COVID-19 induces suppressive myeloid cell production from hematopoietic progenitors in vitro. Sci. Transl. Med. 13, (2021).","DOI":"10.1126\/scitranslmed.abe9599"},{"key":"2021100705200543000_2021.10.04.463121v1.44","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201509-1818OC"},{"key":"2021100705200543000_2021.10.04.463121v1.45","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0000000000005044"},{"key":"2021100705200543000_2021.10.04.463121v1.46","doi-asserted-by":"crossref","first-page":"e57343","DOI":"10.1371\/journal.pone.0057343","article-title":"Induction of SerpinB2 and Th1\/Th2 modulation by SerpinB2 during lentiviral infections in vivo","volume":"8","year":"2013","journal-title":"PLoS One"},{"key":"2021100705200543000_2021.10.04.463121v1.47","doi-asserted-by":"crossref","unstructured":"Zuo, Y. et al. Neutrophil extracellular traps in COVID-19. JCI Insight 5, (2020).","DOI":"10.1172\/jci.insight.138999"},{"key":"2021100705200543000_2021.10.04.463121v1.48","unstructured":"Veras, F. P. et al. SARS-CoV-2-triggered neutrophil extracellular traps mediate COVID-19 pathology. J. Exp. Med. 217, (2020)."},{"key":"2021100705200543000_2021.10.04.463121v1.49","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-76781-0"},{"key":"2021100705200543000_2021.10.04.463121v1.50","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201719"},{"key":"2021100705200543000_2021.10.04.463121v1.51","doi-asserted-by":"publisher","DOI":"10.1101\/2020.10.13.20211425"},{"key":"2021100705200543000_2021.10.04.463121v1.52","doi-asserted-by":"crossref","unstructured":"Hamam, H. J. & Palaniyar, N. Post-Translational Modifications in NETosis and NETs-Mediated Diseases. Biomolecules 9, (2019).","DOI":"10.3390\/biom9080369"},{"key":"2021100705200543000_2021.10.04.463121v1.53","doi-asserted-by":"publisher","DOI":"10.1186\/1710-1492-2-3-98"},{"key":"2021100705200543000_2021.10.04.463121v1.54","doi-asserted-by":"crossref","first-page":"2144","DOI":"10.3389\/fimmu.2019.02144","article-title":"Neutrophils as Suppressors of T Cell Proliferation: Does Age Matter?","volume":"10","year":"2019","journal-title":"Front. Immunol"},{"key":"2021100705200543000_2021.10.04.463121v1.55","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1159\/000487756","article-title":"Neutrophils and Bacterial Immune Evasion","volume":"10","year":"2018","journal-title":"Journal of Innate Immunity"},{"key":"2021100705200543000_2021.10.04.463121v1.56","doi-asserted-by":"publisher","DOI":"10.1186\/s12977-017-0380-3"},{"key":"2021100705200543000_2021.10.04.463121v1.57","doi-asserted-by":"crossref","unstructured":"Kaplonek, P. , et al. Early cross-coronavirus reactive signatures of humoral immunity against COVID-19. Sci. Immunol. https:\/\/www.science.org\/doi\/10.1126\/sciimmunol.abj2901. (2021).","DOI":"10.1101\/2021.05.11.443609"},{"key":"2021100705200543000_2021.10.04.463121v1.58","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2019.05.006"},{"key":"2021100705200543000_2021.10.04.463121v1.59","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-05-718114"},{"key":"2021100705200543000_2021.10.04.463121v1.60","doi-asserted-by":"crossref","unstructured":"Mayadas, T. N. , Cullere, X. & Lowell, C. A. The multifaceted functions of neutrophils. Annu. Rev. Pathol. 9, (2014).","DOI":"10.1146\/annurev-pathol-020712-164023"},{"key":"2021100705200543000_2021.10.04.463121v1.61","doi-asserted-by":"crossref","unstructured":"Anthony, R. M. & Nimmerjahn, F. The role of differential IgG glycosylation in the interaction of antibodies with Fc\u03b3Rs in vivo. Curr. Opin. Organ Transplant. 16, (2011).","DOI":"10.1097\/MOT.0b013e328342538f"},{"key":"2021100705200543000_2021.10.04.463121v1.62","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-00828-7"},{"key":"2021100705200543000_2021.10.04.463121v1.63","doi-asserted-by":"crossref","first-page":"2124","DOI":"10.3389\/fimmu.2020.02124","article-title":"Role of the Intracellular Sodium Homeostasis in Chemotaxis of Activated Murine Neutrophils","volume":"11","year":"2020","journal-title":"Front. Immunol"},{"key":"2021100705200543000_2021.10.04.463121v1.64","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41423-018-0024-0","article-title":"NETosis, complement, and coagulation: a triangular relationship","volume":"16","year":"2019","journal-title":"Cellular and Molecular Immunology"},{"key":"2021100705200543000_2021.10.04.463121v1.65","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.5.3305"},{"key":"2021100705200543000_2021.10.04.463121v1.66","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1089\/jir.2010.0078","article-title":"Interferon-Lambda: A New Addition to an Old Family","volume":"30","year":"2010","journal-title":"Journal of Interferon & Cytokine Research"},{"key":"2021100705200543000_2021.10.04.463121v1.67","first-page":"1","article-title":"Soluble receptor for advanced glycation end products (sRAGE) as a biomarker of COVID-19 disease severity and indicator of the need for mechanical ventilation, ARDS and mortality","volume":"11","year":"2021","journal-title":"Ann. Intensive Care"},{"key":"2021100705200543000_2021.10.04.463121v1.68","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1016\/j.immuni.2020.10.008","article-title":"Plasma Proteomics Identify Biomarkers and Pathogenesis of COVID-19","volume":"53","year":"2020","journal-title":"Immunity"},{"key":"2021100705200543000_2021.10.04.463121v1.69","doi-asserted-by":"crossref","unstructured":"Zhang, Y. , Fear, D. J. , Willis-Owen, S. A. G. , Cookson, W. O. & Moffatt, M. F. Global gene regulation during activation of immunoglobulin class switching in human B cells. Scientific Reports vol. 6 (2016).","DOI":"10.1038\/srep37988"},{"key":"2021100705200543000_2021.10.04.463121v1.70","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.11.5644"},{"key":"2021100705200543000_2021.10.04.463121v1.71","doi-asserted-by":"crossref","unstructured":"Russell, M. W. , Moldoveanu, Z. , Ogra, P. L. & Mestecky, J. Mucosal Immunity in COVID-19: A Neglected but Critical Aspect of SARS-CoV-2 Infection. Front. Immunol. 11, (2020).","DOI":"10.3389\/fimmu.2020.611337"},{"key":"2021100705200543000_2021.10.04.463121v1.72","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciab437"},{"key":"2021100705200543000_2021.10.04.463121v1.73","doi-asserted-by":"crossref","first-page":"6151","DOI":"10.1172\/JCI141374","article-title":"Complement and tissue factor\u2013enriched neutrophil extracellular traps are key drivers in COVID-19 immunothrombosis","volume":"130","year":"2020","journal-title":"J. Clin. Invest"},{"key":"2021100705200543000_2021.10.04.463121v1.74","doi-asserted-by":"crossref","unstructured":"Mutua, V. & Gershwin, L. J. A Review of Neutrophil Extracellular Traps (NETs) in Disease: Potential Anti-NETs Therapeutics. Clin. Rev. Allergy Immunol. 1\u201318 (2020).","DOI":"10.1007\/s12016-020-08804-7"},{"key":"2021100705200543000_2021.10.04.463121v1.75","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1056\/NEJMoa2031893","article-title":"Convalescent Plasma Antibody Levels and the Risk of Death from Covid-19","volume":"384","year":"2021","journal-title":"N. Engl. J. Med"},{"key":"2021100705200543000_2021.10.04.463121v1.76","unstructured":"Kaneko, N. et al. The Loss of Bcl-6 Expressing T Follicular Helper Cells and the Absence of Germinal Centers in COVID-19. SSRN 3652322 (2020)."},{"key":"2021100705200543000_2021.10.04.463121v1.77","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2020-218171"},{"key":"2021100705200543000_2021.10.04.463121v1.78","doi-asserted-by":"crossref","unstructured":"Kridin, K. et al. Tumor necrosis factor inhibitors are associated with a decreased risk of COVID-19-associated hospitalization in patients with psoriasis-A population-based cohort study. Dermatol. Ther. e15003 (2021).","DOI":"10.1111\/dth.15003"},{"key":"2021100705200543000_2021.10.04.463121v1.79","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.05.032"},{"key":"2021100705200543000_2021.10.04.463121v1.80","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2639"},{"key":"2021100705200543000_2021.10.04.463121v1.81","doi-asserted-by":"crossref","unstructured":"Villani, A.-C. et al. Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors. Science 356, (2017).","DOI":"10.1126\/science.aah4573"},{"key":"2021100705200543000_2021.10.04.463121v1.82","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.10.044"},{"key":"2021100705200543000_2021.10.04.463121v1.83","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0550-8"},{"key":"2021100705200543000_2021.10.04.463121v1.84","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2019.02.017"},{"key":"2021100705200543000_2021.10.04.463121v1.85","doi-asserted-by":"publisher","DOI":"10.1101\/2021.07.03.450733"},{"key":"2021100705200543000_2021.10.04.463121v1.86","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8866"},{"key":"2021100705200543000_2021.10.04.463121v1.87","doi-asserted-by":"crossref","unstructured":"Uhlen, M. et al. A genome-wide transcriptomic analysis of protein-coding genes in human blood cells. Science 366, (2019).","DOI":"10.1126\/science.aax9198"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2021.10.04.463121","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T02:14:45Z","timestamp":1768443285000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2021.10.04.463121"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,5]]},"references-count":87,"URL":"https:\/\/doi.org\/10.1101\/2021.10.04.463121","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.1016\/j.xcrm.2022.100779","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2021,10,5]]},"subtype":"preprint"}}