{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T13:03:15Z","timestamp":1789736595164,"version":"4.0.1"},"reference-count":60,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2024,2,17]],"date-time":"2024-02-17T00:00:00Z","timestamp":1708128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UTHSC\/UofM SARS-CoV-2\/COVID-19 Research CORNET Award","award":["2020.02.0131"],"award-info":[{"award-number":["2020.02.0131"]}]},{"name":"UTHSC\/UofM SARS-CoV-2\/COVID-19 Research CORNET Award","award":["Project 861878"],"award-info":[{"award-number":["Project 861878"]}]},{"DOI":"10.13039\/100018227","name":"National Research Foundation of Ukraine","doi-asserted-by":"publisher","award":["2020.02.0131"],"award-info":[{"award-number":["2020.02.0131"]}],"id":[{"id":"10.13039\/100018227","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100018227","name":"National Research Foundation of Ukraine","doi-asserted-by":"publisher","award":["Project 861878"],"award-info":[{"award-number":["Project 861878"]}],"id":[{"id":"10.13039\/100018227","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Union\u2019s Horizon 2020","award":["2020.02.0131"],"award-info":[{"award-number":["2020.02.0131"]}]},{"name":"European Union\u2019s Horizon 2020","award":["Project 861878"],"award-info":[{"award-number":["Project 861878"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Pulmonary fibrosis, severe alveolitis, and the inability to restore alveolar epithelial architecture are primary causes of respiratory failure in fatal COVID-19 cases. However, the factors contributing to abnormal fibrosis in critically ill COVID-19 patients remain unclear. This study analyzed the histopathology of lung specimens from eight COVID-19 and six non-COVID-19 postmortems. We assessed the distribution and changes in extracellular matrix (ECM) proteins, including elastin and collagen, in lung alveoli through morphometric analyses. Our findings reveal the significant degradation of elastin fibers along the thin alveolar walls of the lung parenchyma, a process that precedes the onset of interstitial collagen deposition and widespread intra-alveolar fibrosis. Lungs with collapsed alveoli and organized fibrotic regions showed extensive fragmentation of elastin fibers, accompanied by alveolar epithelial cell death. Immunoblotting of lung autopsy tissue extracts confirmed elastin degradation. Importantly, we found that the loss of elastin was strongly correlated with the induction of neutrophil elastase (NE), a potent protease that degrades ECM. This study affirms the critical role of neutrophils and neutrophil enzymes in the pathogenesis of COVID-19. Consistently, we observed increased staining for peptidyl arginine deiminase, a marker for neutrophil extracellular trap release, and myeloperoxidase, an enzyme-generating reactive oxygen radical, indicating active neutrophil involvement in lung pathology. These findings place neutrophils and elastin degradation at the center of impaired alveolar function and argue that elastolysis and alveolitis trigger abnormal ECM repair and fibrosis in fatal COVID-19 cases. Importantly, this study has implications for severe COVID-19 complications, including long COVID and other chronic inflammatory and fibrotic disorders.<\/jats:p>","DOI":"10.3390\/biom14020236","type":"journal-article","created":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T05:39:56Z","timestamp":1708321196000},"page":"236","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Neutrophil Activity and Extracellular Matrix Degradation: Drivers of Lung Tissue Destruction in Fatal COVID-19 Cases and Implications for Long COVID"],"prefix":"10.3390","volume":"14","author":[{"given":"Teluguakula","family":"Narasaraju","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA"},{"name":"Department of Microbiology, Adichunchanagiri Institute of Medical Sciences, Center for Research and Innovation, Adichunchanagiri University, Mandya 571448, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Indira","family":"Neeli","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheila L.","family":"Criswell","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Health Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amita","family":"Krishnappa","sequence":"additional","affiliation":[{"name":"Department of Pathology, Adichunchanagiri Institute of Medical Sciences, Adichunchanagiri University, Mandya 571448, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzhao","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasuki","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galyna","family":"Bila","sequence":"additional","affiliation":[{"name":"Department of Histology, Cytology, Histology & Embryology, Danylo Halytsky Lviv National Medical University, 79010 Lviv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volodymyr","family":"Vovk","sequence":"additional","affiliation":[{"name":"Department of Pathological Anatomy and Forensic Medicine, Danylo Halytsky Lviv National Medical University, 79010 Lviv, Ukraine"},{"name":"Lviv Regional Pathological Anatomy Office, CU ENT (Pulmonology Lviv Regional Diagnostic Center), 79000 Lviv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zolotukhin","family":"Serhiy","sequence":"additional","affiliation":[{"name":"Lviv Regional Pathological Anatomy Office, CU ENT (Pulmonology Lviv Regional Diagnostic Center), 79000 Lviv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0917-8203","authenticated-orcid":false,"given":"Gary L.","family":"Bowlin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Memphis, Memphis, TN 38152, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4597-5584","authenticated-orcid":false,"given":"Nuala","family":"Meyer","sequence":"additional","affiliation":[{"name":"Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Pulmonary, Allergy, and Critical Care Medicine and Center for Translational Lung Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eline T.","family":"Luning Prak","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"},{"name":"Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8004-282X","authenticated-orcid":false,"given":"Marko","family":"Radic","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2344-1349","authenticated-orcid":false,"given":"Rostyslav","family":"Bilyy","sequence":"additional","affiliation":[{"name":"Department of Histology, Cytology, Histology & Embryology, Danylo Halytsky Lviv National Medical University, 79010 Lviv, Ukraine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2102411","DOI":"10.1183\/13993003.02411-2021","article-title":"Clinical, radiological and pathological findings in patients with persistent lung disease following SARS-CoV-2 infection","volume":"60","author":"Ravaglia","year":"2022","journal-title":"Eur. Respir. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s12931-021-01628-9","article-title":"Tracking the time course of pathological patterns of lung injury in severe COVID-19","volume":"22","author":"Mauad","year":"2021","journal-title":"Respir. Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.medin.2021.02.007","article-title":"Histopathological features in fatal COVID-19 acute respiratory distress syndrome","volume":"45","author":"Merdji","year":"2021","journal-title":"Med. Intensiv."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"106239","DOI":"10.1016\/j.rmed.2020.106239","article-title":"Pulmonary pathology of ARDS in COVID-19: A pathological review for clinicians","volume":"176","author":"Batah","year":"2020","journal-title":"Respir. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"735922","DOI":"10.3389\/fimmu.2021.735922","article-title":"COVID-19 Lung Pathogenesis in SARS-CoV-2 Autopsy Cases","volume":"12","author":"Valdebenito","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1038\/s41422-021-00523-8","article-title":"A cohort autopsy study defines COVID-19 systemic pathogenesis","volume":"31","author":"Yao","year":"2021","journal-title":"Cell Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1111\/his.14249","article-title":"Progression to fibrosing diffuse alveolar damage in a series of 30 minimally invasive autopsies with COVID-19 pneumonia in Wuhan, China","volume":"78","author":"Li","year":"2021","journal-title":"Histopathology"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"E216","DOI":"10.1148\/radiol.2021204482","article-title":"Interstitial Lung Disease after COVID-19 Infection: A Catalog of Uncertainties","volume":"299","author":"Wells","year":"2021","journal-title":"Radiology"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Berezowska, S., Schmid, A., Losmanov\u00e1, T., Trippel, M., Blank, A., Banz, Y., Jakob, S.M., and Langer, R. (2021). Frequency and Significance of Path-ologic Pulmonary Findings in Postmortem Examinations-A Single Center Experience before COVID-19. Diagnostics, 11.","DOI":"10.3390\/diagnostics11050894"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/S2213-2600(20)30222-8","article-title":"Pulmonary fibrosis secondary to COVID-19: A call to arms?","volume":"8","author":"Spagnolo","year":"2020","journal-title":"Lancet Respir. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"E396","DOI":"10.1148\/radiol.2021210834","article-title":"Post-Acute Sequelae of COVID-19 Pneumonia: Six-month Chest CT Follow-up","volume":"301","author":"Caruso","year":"2021","journal-title":"Radiology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1186\/s12967-021-03159-9","article-title":"Virus infection induced pulmonary fibrosis","volume":"19","author":"Huang","year":"2021","journal-title":"J. Transl. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1186\/1465-9921-10-107","article-title":"Pulmonary fibrosis induced by H5N1 viral infection in mice","volume":"10","author":"Qiao","year":"2009","journal-title":"Respir. Res."},{"key":"ref_14","first-page":"2793","article-title":"Thin-Section Computed Tomography Manifestations During Convalescence and Long-Term Follow-Up of Patients with Severe Acute Respiratory Syndrome (SARS)","volume":"22","author":"Wu","year":"2016","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1056\/NEJMsr1408795","article-title":"Middle East Respiratory Syndrome","volume":"376","author":"Arabi","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.mam.2018.08.004","article-title":"Developmental pathways in the pathogenesis of lung fibrosis","volume":"65","author":"Chanda","year":"2019","journal-title":"Mol. Aspects Med."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Sinha, S., Castillo, V., Espinoza, C.R., Tindle, C., Fonseca, A.G., Dan, J.M., Katkar, G.D., Das, S., Sahoo, D., and Ghosh, P. (2022). COVID-19 lung disease shares driver AT2 cytopathic features with Idiopathic pulmonary fibrosis. EBioMedicine, 82.","DOI":"10.1016\/j.ebiom.2022.104185"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"108137","DOI":"10.1016\/j.intimp.2021.108137","article-title":"A possible pathogenic correlation between neutrophil elastase (NE) enzyme and inflammation in the pathogenesis of coronavirus disease 2019 (COVID-19)","volume":"100","author":"Karampoor","year":"2021","journal-title":"Int. Immunopharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Boraldi, F., Lofaro, F.D., Cossarizza, A., and Quaglino, D. (2022). The \u201cElastic Perspective\u201d of SARS-CoV-2 Infection and the Role of Intrinsic and Extrinsic Factors. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031559"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.matbio.2018.01.005","article-title":"Elastin in lung development and disease pathogenesis","volume":"73","author":"Mecham","year":"2018","journal-title":"Matrix Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1183\/09031936.93.03091048","article-title":"Biochemistry and turnover of lung interstitium","volume":"3","author":"Davidson","year":"1990","journal-title":"Eur. Respir. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/S0002-9440(10)61183-2","article-title":"Lysyl oxidase is essential for normal development and function of the respiratory system and for the integrity of elastic and collagen fibers in various tissues","volume":"167","author":"Sormunen","year":"2005","journal-title":"Am. J. Pathol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Mecham, R.P. (2011). Biology of Extracellular Matrix, Springer.","DOI":"10.1002\/0471143030.cb1001s57"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1183\/09031936.00123008","article-title":"Elastin expression in very severe human COPD","volume":"34","author":"Deslee","year":"2009","journal-title":"Eur. Respir. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1172\/JCI115204","article-title":"Marked longevity of human lung parenchymal elastic fibers deduced from prevalence of D-aspartate and nuclear weapons-related radiocarbon","volume":"87","author":"Shapiro","year":"1991","journal-title":"J. Clin. Investig."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s00408-016-9956-2","article-title":"The pattern of elastic fiber breakdown in bleomycin-induced pulmonary fibrosis may reflect microarchitectural changes","volume":"195","author":"Liu","year":"2016","journal-title":"Lung"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e139481","DOI":"10.1172\/JCI139481","article-title":"Neutrophilic inflammation during lung development disrupts elastin assembly and predisposes adult mice to COPD","volume":"131","author":"Benjamin","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1080\/019021499270169","article-title":"The kinetics of elastolysis: Elastin catabolism during experimentally induced fibrosis","volume":"25","author":"Starcher","year":"1999","journal-title":"Exp. Lung Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3125","DOI":"10.1038\/s41418-021-00805-z","article-title":"Patients with COVID-19: In the dark-NETs of neutrophils","volume":"28","author":"Ackermann","year":"2021","journal-title":"Cell Death Differ."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1093\/infdis\/jiab050","article-title":"High Levels of Neutrophil Extracellular Traps Persist in the Lower Respiratory Tract of Critically Ill Patients with Coronavirus Disease 2019","volume":"223","author":"Ouwendijk","year":"2021","journal-title":"J. Infect. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1043219","DOI":"10.3389\/fimmu.2022.1043219","article-title":"Blood transcriptome responses in patients correlate with severity of COVID-19 disease","volume":"13","author":"Wang","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"4201","DOI":"10.1038\/s41467-023-40012-7","article-title":"Chronic inflammation, neutrophil activity, and autoreactivity splits long COVID","volume":"14","author":"Woodruff","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"H610","DOI":"10.1152\/ajpheart.00598.2020","article-title":"Injury-specific inflammation leads to organ-specific fibrosis","volume":"319","author":"Cakir","year":"2020","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1186\/s12931-018-0747-6","article-title":"Increased circulating desmosine and age-dependent elastinolysis in idiopathic pulmonary fibrosis","volume":"19","author":"Drent","year":"2018","journal-title":"Respir. Res."},{"key":"ref_35","first-page":"E560","article-title":"\u03b11-Antitrypsin A treatment attenuates neutrophil elastase accumulation and enhances insulin sensitivity in adipose tissue of mice fed a high-fat diet","volume":"321","author":"Masson","year":"2021","journal-title":"Am. J. Physiol. Metab."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5417","DOI":"10.1038\/s41467-021-25509-3","article-title":"New-onset IgG autoantibodies in hospitalized patients with COVID-19","volume":"12","author":"Chang","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e155114","DOI":"10.1172\/JCI155114","article-title":"A randomized controlled study of convalescent plasma for individuals hospitalized with COVID-19 pneumonia","volume":"131","author":"Bar","year":"2021","journal-title":"J. Clin. Investig."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2004165","DOI":"10.1183\/13993003.04165-2020","article-title":"Collapse in-duration of alveoli is an ultrastructural finding in a COVID-19 patient","volume":"57","author":"Ochs","year":"2021","journal-title":"Eur. Respir. J."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.medj.2022.03.001","article-title":"A randomized, double-blind, place-bo-controlled trial of intravenous alpha-1 antitrypsin for ARDS secondary to COVID-19","volume":"3","author":"McElvaney","year":"2022","journal-title":"Med"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.ejim.2022.07.009","article-title":"The COVID-19 pandemic\u2014How many times were we warned before?","volume":"105","author":"Mahroum","year":"2022","journal-title":"Eur. J. Intern. Med."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Voskarides, K. (2022). SARS-CoV-2: Tracing the origin, tracking the evolution. BMC Med. Genomics, 15.","DOI":"10.1186\/s12920-022-01208-w"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Nugent, M.A. (2022). The Future of the COVID-19 Pandemic: How Good (or Bad) Can the SARS-CoV2 Spike Protein Get?. Cells, 11.","DOI":"10.3390\/cells11050855"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/S0046-8177(86)80653-0","article-title":"Pathogenesis of pulmonary fibrosis","volume":"17","author":"Burkhardt","year":"1986","journal-title":"Hum. Pathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1159\/000398287","article-title":"Pathogenesis of interstitial fibrosis of the lung","volume":"8","author":"Spencer","year":"1975","journal-title":"Progr Respir. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1164\/rccm.201508-1638OC","article-title":"Stretch-induced Activation of Transforming Growth Factor-\u03b21 in Pulmonary Fibrosis","volume":"194","author":"Froese","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"eabj7790","DOI":"10.1126\/scitranslmed.abj7790","article-title":"Lung epithelial and endothelial damage, loss of tissue repair, inhibition of fibrinolysis, and cellular senescence in fatal COVID-19","volume":"13","author":"Walters","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_47","first-page":"A5333","article-title":"Elastin degradative products induce myofibroblast differentiation","volume":"199","author":"Nagel","year":"2019","journal-title":"Am. J. Resp. Crit. Care Med."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Neeli, I., Moarefian, M., Kuseladass, J., Dwivedi, N., Jones, C., and Radic, M. (2023). Neutrophil attachment via Mac-1 (\u03b1M\u03b22; CD11b\/CD18; CR3) integrins induces PAD4 deimination of profilin and histone H3. Philos. Trans. R. Soc. B Biol. Sci., 378.","DOI":"10.1098\/rstb.2022.0247"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1254310","DOI":"10.3389\/fimmu.2023.1254310","article-title":"Neutrophil extracellular traps and long COVID","volume":"14","author":"Shafqat","year":"2023","journal-title":"Front. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e211","DOI":"10.1017\/S0950268820002071","article-title":"Ratios of neutrophil-to-lymphocyte and platelet-to-lymphocyte predict all-cause mortality in inpatients with coronavirus disease 2019 (COVID-19): A retrospective cohort study in a single medical centre","volume":"148","author":"Wang","year":"2020","journal-title":"Epidemiol. Infect."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1111\/jth.14768","article-title":"Abnormal Coagulation Parameters Are Associated with Poor Prognosis in Patients with Novel Coronavirus Pneumonia","volume":"18","author":"Tang","year":"2020","journal-title":"J. Thromb. Haemost."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e20200652","DOI":"10.1084\/jem.20200652","article-title":"Targeting potential drivers of COVID-19: Neutrophil extracellular traps","volume":"217","author":"Barnes","year":"2020","journal-title":"J. Exp. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1007\/s11239-020-02324-z","article-title":"Neutrophil extracellular traps and thrombosis in COVID-19","volume":"51","author":"Zuo","year":"2021","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_54","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","author":"Middleton","year":"2020","journal-title":"Blood"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1038\/s41419-023-05890-1","article-title":"RNF128 regulates neutrophil infiltration and myeloperoxidase functions to prevent acute lung injury","volume":"14","author":"Liu","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1111\/j.0022-202X.2004.22401.x","article-title":"Deficiency of tenascin-X causes abnormalities in dermal elastic fiber morphology","volume":"122","author":"Zweers","year":"2004","journal-title":"J. Invest. Dermatol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/s12931-015-0220-8","article-title":"Second harmonic generation microscopy reveals altered collagen microstructure in usual interstitial pneumonia versus healthy lung","volume":"16","author":"Kottmann","year":"2015","journal-title":"Respir. Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"362","DOI":"10.3389\/fimmu.2017.00362","article-title":"B Cell Tolerance to Deiminated Histones in BALB\/c, C57BL\/6, and Autoimmune-Prone Mouse Strains","volume":"8","author":"Dwivedi","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/978-1-4615-9355-3_33","article-title":"Enzyme-linked immunoassay for human granulocyte elastase in complex with alpha 1-proteinase inhibitor","volume":"167","author":"Neumann","year":"1984","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Engelmaier, A., and Weber, A. (2022). Sensitive and specific measurement of alpha1-antitrypsin activity with an elastase complex formation immunosorbent assay (ECFISA). J. Pharm. Biomed. Anal., 209.","DOI":"10.1016\/j.jpba.2021.114476"}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/2\/236\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:01:25Z","timestamp":1760104885000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/14\/2\/236"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,17]]},"references-count":60,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["biom14020236"],"URL":"https:\/\/doi.org\/10.3390\/biom14020236","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,17]]}}}