{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:01:45Z","timestamp":1790841705346,"version":"4.1.0"},"reference-count":312,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T00:00:00Z","timestamp":1626307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002261","name":"Russian Foundation for Basic Research","doi-asserted-by":"publisher","award":["21-51-55003"],"award-info":[{"award-number":["21-51-55003"]}],"id":[{"id":"10.13039\/501100002261","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82161138003"],"award-info":[{"award-number":["82161138003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Government contract of the Institute of Immunology and Physiology","award":["\u0410\u0410\u0410\u0410-\u041021-121012090091-6"],"award-info":[{"award-number":["\u0410\u0410\u0410\u0410-\u041021-121012090091-6"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The COVID-19 pandemic examines not only the state of actual health care but also the state of fundamental medicine in various countries. Pro-inflammatory processes extend far beyond the classical concepts of inflammation. They manifest themselves in a variety of ways, beginning with extreme physiology, then allostasis at low-grade inflammation, and finally the shockogenic phenomenon of \u201cinflammatory systemic microcirculation\u201d. The pathogenetic core of critical situations, including COVID-19, is this phenomenon. Microcirculatory abnormalities, on the other hand, lie at the heart of a specific type of general pathological process known as systemic inflammation (SI). Systemic inflammatory response, cytokine release, cytokine storm, and thrombo-inflammatory syndrome are all terms that refer to different aspects of SI. As a result, the metabolic syndrome model does not adequately reflect the pathophysiology of persistent low-grade systemic inflammation (ChSLGI). Diseases associated with ChSLGI, on the other hand, are risk factors for a severe COVID-19 course. The review examines the role of hypoxia, metabolic dysfunction, scavenger receptors, and pattern-recognition receptors, as well as the processes of the hemophagocytic syndrome, in the systemic alteration and development of SI in COVID-19.<\/jats:p>","DOI":"10.3390\/ijms22147582","type":"journal-article","created":{"date-parts":[[2021,7,15]],"date-time":"2021-07-15T09:32:07Z","timestamp":1626341527000},"page":"7582","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Problems of Pathogenesis and Pathogenetic Therapy of COVID-19 from the Perspective of the General Theory of Pathological Systems (General Pathological Processes)"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7145-2376","authenticated-orcid":false,"given":"Evgenii","family":"Gusev","sequence":"first","affiliation":[{"name":"Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, 620049 Ekaterinburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey","family":"Sarapultsev","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, 620049 Ekaterinburg, Russia"},{"name":"School of Medical Biology, South Ural State University, 454080 Chelyabinsk, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desheng","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 200092, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeriy","family":"Chereshnev","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, 620049 Ekaterinburg, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1080\/01652176.2020.1727993","article-title":"Emerging Novel Coronavirus (2019-NCoV)-Current Scenario, Evolutionary Perspective Based on Genome Analysis and Recent Developments","volume":"40","author":"Malik","year":"2020","journal-title":"Vet. Q."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Bellocchio, L., Bordea, I.R., Ballini, A., Lorusso, F., Hazballa, D., Isacco, C.G., Malcangi, G., Inchingolo, A.D., Dipalma, G., and Inchingolo, F. (2020). Environmental Issues and Neurological Manifestations Associated with COVID-19 Pandemic: New Aspects of the Disease?. Int. J. Environ. Res. Public Health, 17.","DOI":"10.3390\/ijerph17218049"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e00028","DOI":"10.1128\/CMR.00028-20","article-title":"Coronavirus Disease 2019-COVID-19","volume":"33","author":"Dhama","year":"2020","journal-title":"Clin. Microbiol Rev."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zotova, N.V., Chereshnev, V.A., and Gusev, E.Y. (2016). Systemic Inflammation: Methodological Approaches to Identification of the Common Pathological Process. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0155138"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"251","DOI":"10.2174\/1381612825666190319114641","article-title":"Cellular Stress and General Pathological Processes","volume":"25","author":"Gusev","year":"2019","journal-title":"Curr. Pharm. Des."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1016\/j.it.2020.10.004","article-title":"Mechanisms of SARS-CoV-2 Transmission and Pathogenesis","volume":"41","author":"Harrison","year":"2020","journal-title":"Trends Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4587","DOI":"10.1021\/acs.jproteome.0c00654","article-title":"Molecular Simulations and Network Modeling Reveal an Allosteric Signaling in the SARS-CoV-2 Spike Proteins","volume":"19","author":"Verkhivker","year":"2020","journal-title":"J. Proteome Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"14838","DOI":"10.1074\/jbc.M200581200","article-title":"Hydrolysis of Biological Peptides by Human Angiotensin-Converting Enzyme-Related Carboxypeptidase","volume":"277","author":"Vickers","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1111\/bph.12159","article-title":"ACE2, Angiotensin-(1-7) and Mas Receptor Axis in Inflammation and Fibrosis","volume":"169","author":"Silveira","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1080\/17476348.2020.1804365","article-title":"Mortality in COVID-19 Patients with Acute Respiratory Distress Syndrome and Corticosteroids Use: A Systematic Review and Meta-Analysis","volume":"14","author":"Hasan","year":"2020","journal-title":"Expert Rev. Respir. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1016\/S2213-2600(20)30304-0","article-title":"COVID-19-Associated Acute Respiratory Distress Syndrome: Is a Different Approach to Management Warranted?","volume":"8","author":"Fan","year":"2020","journal-title":"Lancet Respir. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1016\/S2213-2600(20)30370-2","article-title":"Pathophysiology of COVID-19-Associated Acute Respiratory Distress Syndrome: A Multicentre Prospective Observational Study","volume":"8","author":"Grasselli","year":"2020","journal-title":"Lancet Respir. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/S2213-2600(20)30505-1","article-title":"Pathophysiology of COVID-19-Associated Acute Respiratory Distress Syndrome","volume":"9","author":"Camporota","year":"2021","journal-title":"Lancet Respir. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1007\/s12185-020-03029-y","article-title":"COVID-19-Associated Coagulopathy and Disseminated Intravascular Coagulation","volume":"113","author":"Asakura","year":"2021","journal-title":"Int. J. Hematol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1016\/S0140-6736(03)13412-5","article-title":"Clinical Progression and Viral Load in a Community Outbreak of Coronavirus-Associated SARS Pneumonia: A Prospective Study","volume":"361","author":"Peiris","year":"2003","journal-title":"Lancet"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1016\/j.jmii.2020.04.015","article-title":"ACE2 Receptor Polymorphism: Susceptibility to SARS-CoV-2, Hypertension, Multi-Organ Failure, and COVID-19 Disease Outcome","volume":"53","author":"Devaux","year":"2020","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Madabhavi, I., Sarkar, M., and Kadakol, N. (2020). COVID-19: A Review. Monaldi Arch. Chest Dis., 90.","DOI":"10.4081\/monaldi.2020.1298"},{"key":"ref_18","first-page":"e13165","article-title":"Obesity and Disease Severity Among Patients With COVID-19","volume":"13","author":"Motaib","year":"2021","journal-title":"Cureus"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Hilser, J.R., Han, Y., Biswas, S., Gukasyan, J., Cai, Z., Zhu, R., Tang, W.H.W., Deb, A., Lusis, A.J., and Hartiala, J.A. (2021). Association of Serum HDL-Cholesterol and Apolipoprotein A1 Levels with Risk of Severe SARS-CoV-2 Infection. J. Lipid Res., 62.","DOI":"10.1016\/j.jlr.2021.100061"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"O\u2019Hearn, M., Liu, J., Cudhea, F., Micha, R., and Mozaffarian, D. (2021). Coronavirus Disease 2019 Hospitalizations Attributable to Cardiometabolic Conditions in the United States: A Comparative Risk Assessment Analysis. J. Am. Heart Assoc., 10.","DOI":"10.1161\/JAHA.120.019259"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/s41574-020-00462-1","article-title":"Global Pandemics Interconnected\u2014Obesity, Impaired Metabolic Health and COVID-19","volume":"17","author":"Stefan","year":"2021","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"923","DOI":"10.4158\/EP-2020-0302","article-title":"Covid-19 & Obesity: Beyond Bmi","volume":"26","author":"Nadolsky","year":"2020","journal-title":"Endocr. Pract."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1002\/iid3.404","article-title":"Age-Related Differences in the Immune Response Could Contribute to Determine the Spectrum of Severity of COVID-19","volume":"9","author":"Costagliola","year":"2021","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.burnso.2020.11.003","article-title":"A Case Series of Concomitant Burn and COVID-19","volume":"5","author":"Hesamirostami","year":"2021","journal-title":"Burns Open"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1007\/s13304-020-00909-0","article-title":"Complications and Mortality in a Cohort of Patients Undergoing Emergency and Elective Surgery with Perioperative SARS-CoV-2 Infection: An Italian Multicenter Study. Teachings of Phase 1 to Be Brought in Phase 2 Pandemic","volume":"73","author":"Sartori","year":"2021","journal-title":"Updates Surg."},{"key":"ref_26","first-page":"99","article-title":"Virus-Host Interactome and Proteomic Survey Reveal Potential Virulence Factors Influencing SARS-CoV-2","volume":"2","author":"Li","year":"2021","journal-title":"Pathog. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"307","DOI":"10.4049\/jimmunol.2000513","article-title":"Inflammasomes and Pyroptosis as Therapeutic Targets for COVID-19","volume":"205","author":"Yap","year":"2020","journal-title":"J. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Lin, L., Luo, S., Qin, R., Yang, M., Wang, X., Yang, Q., Zhang, Y., Wang, Q., Zhu, R., and Fan, H. (2020). Long-Term Infection of SARS-CoV-2 Changed the Body\u2019s Immune Status. Clin. Immunol., 218.","DOI":"10.1016\/j.clim.2020.108524"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.imlet.2020.09.004","article-title":"Interplays between Inflammasomes and Viruses, Bacteria (Pathogenic and Probiotic), Yeasts and Parasites","volume":"228","author":"Antushevich","year":"2020","journal-title":"Immunol. Lett."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Wilson, J.G., Simpson, L.J., Ferreira, A.-M., Rustagi, A., Roque, J., Asuni, A., Ranganath, T., Grant, P.M., Subramanian, A., and Rosenberg-Hasson, Y. (2020). Cytokine Profile in Plasma of Severe COVID-19 Does Not Differ from ARDS and Sepsis. JCI Insight, 5.","DOI":"10.1172\/jci.insight.140289"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.cytogfr.2020.05.003","article-title":"The Cytokine Storm in COVID-19: An Overview of the Involvement of the Chemokine\/Chemokine-Receptor System","volume":"53","author":"Coperchini","year":"2020","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.1016\/j.ajpath.2020.06.010","article-title":"Eicosanoids: The Overlooked Storm in Coronavirus Disease 2019 (COVID-19)?","volume":"190","author":"Hammock","year":"2020","journal-title":"Am. J. Pathol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Zhao, Y., Qin, L., Zhang, P., Li, K., Liang, L., Sun, J., Xu, B., Dai, Y., Li, X., and Zhang, C. (2020). Longitudinal COVID-19 Profiling Associates IL-1RA and IL-10 with Disease Severity and RANTES with Mild Disease. JCI Insight, 5.","DOI":"10.1172\/jci.insight.139834"},{"key":"ref_34","first-page":"E005","article-title":"Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia","volume":"43","author":"Chen","year":"2020","journal-title":"Chin. J. Tuberc. Respir. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"827","DOI":"10.3389\/fimmu.2020.00827","article-title":"Reduction and Functional Exhaustion of T Cells in Patients with Coronavirus Disease 2019 (COVID-19)","volume":"11","author":"Diao","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/S0140-6736(20)30183-5","article-title":"Clinical Features of Patients Infected with 2019 Novel Coronavirus in Wuhan, China","volume":"395","author":"Huang","year":"2020","journal-title":"Lancet"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1080\/22221751.2020.1770129","article-title":"Profiling Serum Cytokines in COVID-19 Patients Reveals IL-6 and IL-10 Are Disease Severity Predictors","volume":"9","author":"Han","year":"2020","journal-title":"Emerg. Microbes Infect."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1007\/s00134-020-05991-x","article-title":"Clinical Predictors of Mortality Due to COVID-19 Based on an Analysis of Data of 150 Patients from Wuhan, China","volume":"46","author":"Ruan","year":"2020","journal-title":"Intensive Care Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1080\/22221751.2020.1747363","article-title":"Transcriptomic Characteristics of Bronchoalveolar Lavage Fluid and Peripheral Blood Mononuclear Cells in COVID-19 Patients","volume":"9","author":"Xiong","year":"2020","journal-title":"Emerg. Microbes Infect."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1002\/JLB.3COVR0520-272R","article-title":"Cytokine Storm and Leukocyte Changes in Mild versus Severe SARS-CoV-2 Infection: Review of 3939 COVID-19 Patients in China and Emerging Pathogenesis and Therapy Concepts","volume":"108","author":"Wang","year":"2020","journal-title":"J. Leukoc. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1093\/cid\/ciaa248","article-title":"Dysregulation of Immune Response in Patients with Coronavirus 2019 (COVID-19) in Wuhan, China","volume":"71","author":"Qin","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1111\/imm.13223","article-title":"Immunopathological Characteristics of Coronavirus Disease 2019 Cases in Guangzhou, China","volume":"160","author":"Tan","year":"2020","journal-title":"Immunology"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1002\/jmv.25770","article-title":"Diagnostic Utility of Clinical Laboratory Data Determinations for Patients with the Severe COVID-19","volume":"92","author":"Gao","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Liu, F., Li, L., Xu, M., Wu, J., Luo, D., Zhu, Y., Li, B., Song, X., and Zhou, X. (2020). Prognostic Value of Interleukin-6, C-Reactive Protein, and Procalcitonin in Patients with COVID-19. J. Clin. Virol., 127.","DOI":"10.1016\/j.jcv.2020.104370"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2620","DOI":"10.1172\/JCI137244","article-title":"Clinical and Immunological Features of Severe and Moderate Coronavirus Disease 2019","volume":"130","author":"Chen","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Liu, J., Li, S., Liu, J., Liang, B., Wang, X., Wang, H., Li, W., Tong, Q., Yi, J., and Zhao, L. (2020). Longitudinal Characteristics of Lymphocyte Responses and Cytokine Profiles in the Peripheral Blood of SARS-CoV-2 Infected Patients. EBioMedicine, 55.","DOI":"10.1016\/j.ebiom.2020.102763"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Liu, T., Zhang, J., Yang, Y., Ma, H., Li, Z., Zhang, J., Cheng, J., Zhang, X., Zhao, Y., and Xia, Z. (2020). The Role of Interleukin-6 in Monitoring Severe Case of Coronavirus Disease 2019. EMBO Mol. Med., 12.","DOI":"10.15252\/emmm.202012421"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Gong, J., Dong, H., Xia, Q.-S., Huang, Z.-Y., Wang, D.-K., Zhao, Y., Liu, W.-H., Tu, S.-H., Zhang, M.-M., and Wang, Q. (2020). Correlation Analysis between Disease Severity and Inflammation-Related Parameters in Patients with COVID-19: A Retrospective Study. BMC Infect. Dis., 20.","DOI":"10.1186\/s12879-020-05681-5"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1093\/cid\/ciaa272","article-title":"Clinical Features of 69 Cases with Coronavirus Disease 2019 in Wuhan, China","volume":"71","author":"Wang","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1937","DOI":"10.1093\/cid\/ciaa449","article-title":"Detectable Serum Severe Acute Respiratory Syndrome Coronavirus 2 Viral Load (RNAemia) Is Closely Correlated with Drastically Elevated Interleukin 6 Level in Critically Ill Patients with Coronavirus Disease 2019","volume":"71","author":"Chen","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1093\/cid\/ciaa462","article-title":"Downregulated Gene Expression Spectrum and Immune Responses Changed During the Disease Progression in Patients With COVID-19","volume":"71","author":"Ouyang","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1038\/s41423-020-00522-6","article-title":"Sepsis-Associated Severe Interleukin-6 Storm in Critical Coronavirus Disease 2019","volume":"17","author":"Huang","year":"2020","journal-title":"Cell. Mol. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.jaci.2020.04.006","article-title":"Risk Factors for Severity and Mortality in Adult COVID-19 Inpatients in Wuhan","volume":"146","author":"Li","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.jaci.2020.04.027","article-title":"Plasma IP-10 and MCP-3 Levels Are Highly Associated with Disease Severity and Predict the Progression of COVID-19","volume":"146","author":"Yang","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s10456-020-09753-7","article-title":"Microvascular Dysfunction in COVID-19: The MYSTIC Study","volume":"24","author":"Rovas","year":"2021","journal-title":"Angiogenesis"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Li, M., Guo, W., Dong, Y., Wang, X., Dai, D., Liu, X., Wu, Y., Li, M., Zhang, W., and Zhou, H. (2020). Elevated Exhaustion Levels of NK and CD8+ T Cells as Indicators for Progression and Prognosis of COVID-19 Disease. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.580237"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"13","DOI":"10.4149\/gpb_2019043","article-title":"Integral Estimation of Systemic Inflammatory Response under Sepsis","volume":"39","author":"Zotova","year":"2020","journal-title":"Gen. Physiol. Biophys."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1146\/annurev-physiol-022516-034339","article-title":"Macrophage Polarization","volume":"79","author":"Murray","year":"2017","journal-title":"Annu. Rev. Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Olmos, G., and Llad\u00f3, J. (2014). Tumor Necrosis Factor Alpha: A Link between Neuroinflammation and Excitotoxicity. Mediat. Inflamm., 2014.","DOI":"10.1155\/2014\/861231"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1016\/j.biopsych.2008.11.029","article-title":"Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression","volume":"65","author":"Miller","year":"2009","journal-title":"Biol. Psychiatry"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1042\/BST0351122","article-title":"Interleukin-1 and Inflammatory Neurodegeneration","volume":"35","author":"Simi","year":"2007","journal-title":"Biochem. Soc. Trans."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"de la Rica, R., Borges, M., and Gonzalez-Freire, M. (2020). COVID-19: In the Eye of the Cytokine Storm. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.558898"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Chauhan, A., Kaur, R., Chakrbarti, P., and Pal, A. (2021). \u201cSilent Hypoxemia\u201d Leads to Vicious Cycle of Infection, Coagulopathy and Cytokine Storm in COVID-19: Can Prophylactic Oxygen Therapy Prevent It?. Indian J. Clin. Biochem., 1\u20135.","DOI":"10.1007\/s12291-021-00967-0"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1016\/j.mayocp.2020.04.006","article-title":"Association Between Hypoxemia and Mortality in Patients With COVID-19","volume":"95","author":"Xie","year":"2020","journal-title":"Mayo Clin. Proc."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"AbdelMassih, A., Yacoub, E., Husseiny, R.J., Kamel, A., Hozaien, R., El Shershaby, M., Rajab, M., Yacoub, S., Eid, M.A., and Elahmady, M. (2021). Hypoxia-Inducible Factor (HIF): The Link between Obesity and COVID-19. Obes. Med., 22.","DOI":"10.1016\/j.obmed.2020.100317"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1016\/j.mayocp.2020.09.015","article-title":"Progressive Hypoxia: A Pivotal Pathophysiologic Mechanism of COVID-19 Pneumonia","volume":"95","author":"Somers","year":"2020","journal-title":"Mayo Clin. Proc."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/10409238.2013.838205","article-title":"Transcriptional Regulation by Hypoxia Inducible Factors","volume":"49","author":"Dengler","year":"2014","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2282","DOI":"10.1016\/j.bbrc.2017.12.084","article-title":"Hypoxia-Increased RAGE Expression Regulates Chemotaxis and pro-Inflammatory Cytokines Release through Nuclear Translocation of NF-\u03ba B and HIF1\u03b1 in THP-1 cells","volume":"495","author":"Bai","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1786","DOI":"10.4049\/jimmunol.0903244","article-title":"Acute Hypoxia Induces HIF-Independent Monocyte Adhesion to Endothelial Cells through Increased Intercellular Adhesion Molecule-1 Expression: The Role of Hypoxic Inhibition of Prolyl Hydroxylase Activity for the Induction of NF-Kappa, B","volume":"185","author":"Winning","year":"2010","journal-title":"J. Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"L360","DOI":"10.1152\/ajplung.00158.2002","article-title":"Decreased Alveolar Oxygen Induces Lung Inflammation","volume":"284","author":"Madjdpour","year":"2003","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_71","first-page":"R160","article-title":"Hypoxemia in the Absence of Blood Loss or Significant Hypotension Causes Inflammatory Cytokine Release","volume":"269","author":"Ertel","year":"1995","journal-title":"Am. J. Physiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4763","DOI":"10.1073\/pnas.1620458114","article-title":"Activation of NLRP3 Inflammasome Complex Potentiates Venous Thrombosis in Response to Hypoxia","volume":"114","author":"Gupta","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Zonneveld, M.I., Keulers, T.G.H., and Rouschop, K.M.A. (2019). Extracellular Vesicles as Transmitters of Hypoxia Tolerance in Solid Cancers. Cancers, 11.","DOI":"10.3390\/cancers11020154"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1161\/01.RES.0000093984.48643.D7","article-title":"Hypoxia-Inducible Factor-1 Mediates Activation of Cultured Vascular Endothelial Cells by Inducing Multiple Angiogenic Factors","volume":"93","author":"Yamakawa","year":"2003","journal-title":"Circ. Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1038\/s41401-020-00554-8","article-title":"Hypoxia, HIF-1\u03b1, and COVID-19: From Pathogenic Factors to Potential Therapeutic Targets","volume":"41","author":"Serebrovska","year":"2020","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"e13201","DOI":"10.1111\/acel.13201","article-title":"Rapid Senescence-like Response after Acute Injury","volume":"19","author":"Chu","year":"2020","journal-title":"Aging Cell"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1056\/NEJMra1705649","article-title":"Hemorrhagic Shock","volume":"378","author":"Cannon","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"6470","DOI":"10.4049\/jimmunol.0802378","article-title":"Hypoxia-Inducible Factor (HIF) 1alpha Accumulation and HIF Target Gene Expression Are Impaired after Induction of Endotoxin Tolerance","volume":"182","author":"Frede","year":"2009","journal-title":"J. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Hern\u00e1ndez, A., Geng, Y., Sep\u00falveda, R., Sol\u00eds, N., Torres, J., Arab, J.P., Barrera, F., Cabrera, D., Moshage, H., and Arrese, M. (2020). Chemical Hypoxia Induces Pro-Inflammatory Signals in Fat-Laden Hepatocytes and Contributes to Cellular Crosstalk with Kupffer Cells through Extracellular Vesicles. Biochim. Biophys. Acta Mol. Basis Dis., 1866.","DOI":"10.1016\/j.bbadis.2020.165753"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1074\/jbc.M115.686709","article-title":"Hypoxia Potentiates Palmitate-Induced Pro-Inflammatory Activation of Primary Human Macrophages","volume":"291","author":"Snodgrass","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"7211","DOI":"10.4049\/jimmunol.177.10.7211","article-title":"A Novel Role of Hypoxia-Inducible Factor in Cobalt Chloride- and Hypoxia-Mediated Expression of IL-8 Chemokine in Human Endothelial Cells","volume":"177","author":"Kim","year":"2006","journal-title":"J. Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.3389\/fphys.2020.01035","article-title":"HIF-1\u03b1 as a Mediator of Insulin Resistance, T2DM, and Its Complications: Potential Links With Obstructive Sleep Apnea","volume":"11","author":"Gabryelska","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.cell.2010.01.022","article-title":"Pattern Recognition Receptors and Inflammation","volume":"140","author":"Takeuchi","year":"2010","journal-title":"Cell"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/s41577-019-0215-7","article-title":"DAMP-Sensing Receptors in Sterile Inflammation and Inflammatory Diseases","volume":"20","author":"Gong","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/978-981-15-0606-2_6","article-title":"The Interplay Between Pattern Recognition Receptors and Autophagy in Inflammation","volume":"1209","author":"Zhu","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2379","DOI":"10.3389\/fimmu.2018.02379","article-title":"Pattern Recognition Receptors and the Host Cell Death Molecular Machinery","volume":"9","author":"Adjemian","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"6258","DOI":"10.1096\/fj.201800691R","article-title":"Peptidylarginine Deiminase 4: A Nuclear Button Triggering Neutrophil Extracellular Traps in Inflammatory Diseases and Aging","volume":"32","author":"Wong","year":"2018","journal-title":"FASEB J."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Chen, J., Hall, S., and Vitetta, L. (2021). Altered Gut Microbial Metabolites Could Mediate the Effects of Risk Factors in Covid-19. Rev. Med. Virol., e2211.","DOI":"10.1002\/rmv.2211"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"99","DOI":"10.3389\/fmed.2021.640073","article-title":"New Insights into the Physiopathology of COVID-19: SARS-CoV-2-Associated Gastrointestinal Illness","volume":"8","author":"Devaux","year":"2021","journal-title":"Front. Med."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Aboudounya, M.M., and Heads, R.J. (2021). COVID-19 and Toll-Like Receptor 4 (TLR4): SARS-CoV-2 May Bind and Activate TLR4 to Increase ACE2 Expression, Facilitating Entry and Causing Hyperinflammation. Mediat. Inflamm., 2021.","DOI":"10.1155\/2021\/8874339"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2105","DOI":"10.1002\/jmv.25987","article-title":"In Silico Studies on the Comparative Characterization of the Interactions of SARS-CoV-2 Spike Glycoprotein with ACE-2 Receptor Homologs and Human TLRs","volume":"92","author":"Choudhury","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"7","DOI":"10.15789\/1563-0625-PAP-1893","article-title":"Physiological and pathogenic role of scavenger receptors in humans","volume":"22","author":"Gusev","year":"2020","journal-title":"Med. Immunol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"3775","DOI":"10.4049\/jimmunol.1700373","article-title":"A Consensus Definitive Classification of Scavenger Receptors and Their Roles in Health and Disease","volume":"198","author":"PrabhuDas","year":"2017","journal-title":"J. Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/S0018-506X(02)00024-7","article-title":"The Concept of Allostasis in Biology and Biomedicine","volume":"43","author":"McEwen","year":"2003","journal-title":"Horm. Behav."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Amraie, R., Napoleon, M.A., Yin, W., Berrigan, J., Suder, E., Zhao, G., Olejnik, J., Gummuluru, S., Muhlberger, E., and Chitalia, V. (2020). CD209L\/L-SIGN and CD209\/DC-SIGN Act as Receptors for SARS-CoV-2 and Are Differentially Expressed in Lung and Kidney Epithelial and Endothelial Cells. bioRxiv.","DOI":"10.1101\/2020.06.22.165803"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1391","DOI":"10.1038\/s42255-020-00324-0","article-title":"HDL-Scavenger Receptor B Type 1 Facilitates SARS-CoV-2 Entry","volume":"2","author":"Wei","year":"2020","journal-title":"Nat. Metab."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Al-Banna, N., and Lehmann, C. (2013). Oxidized LDL and LOX-1 in Experimental Sepsis. Mediat. Inflamm., 2013.","DOI":"10.1155\/2013\/761789"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1186\/1479-5876-7-17","article-title":"RAGE (Receptor for Advanced Glycation Endproducts), RAGE Ligands, and Their Role in Cancer and Inflammation","volume":"7","author":"Sparvero","year":"2009","journal-title":"J. Transl. Med."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1641","DOI":"10.1172\/JCI200418704","article-title":"Receptor for Advanced Glycation End Products (RAGE) Regulates Sepsis but Not the Adaptive Immune Response","volume":"113","author":"Liliensiek","year":"2004","journal-title":"J. Clin. Investig."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1478-811X-7-12","article-title":"The Receptor RAGE: Bridging Inflammation and Cancer","volume":"7","author":"Riehl","year":"2009","journal-title":"Cell Commun. Signal."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"16","DOI":"10.5847\/wjem.j.issn.1920-8642.2014.01.002","article-title":"Presepsin as a Novel Sepsis Biomarker","volume":"5","author":"Zou","year":"2014","journal-title":"World J. Emerg. Med."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Feng, L., Zhou, X., Su, L.-X., Feng, D., Jia, Y.-H., and Xie, L.-X. (2012). Clinical Significance of Soluble Hemoglobin Scavenger Receptor CD163 (SCD163) in Sepsis, a Prospective Study. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0038400"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1515\/cclm-2013-0451","article-title":"A Soluble Form of the Macrophage-Related Mannose Receptor (MR\/CD206) Is Present in Human Serum and Elevated in Critical Illness","volume":"52","author":"Rafique","year":"2014","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1002\/jmv.26164","article-title":"Presepsin as a Predictive Biomarker of Severity in COVID-19: A Case Series","volume":"93","author":"Fukada","year":"2021","journal-title":"J. Med. Virol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.cca.2020.04.020","article-title":"Presepsin in Risk Stratification of SARS-CoV-2 Patients","volume":"507","author":"Zaninotto","year":"2020","journal-title":"Clin. Chim. Acta"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Zingaropoli, M.A., Nijhawan, P., Carraro, A., Pasculli, P., Zuccal\u00e0, P., Perri, V., Marocco, R., Kertusha, B., Siccardi, G., and Del Borgo, C. (2021). Increased SCD163 and SCD14 Plasmatic Levels and Depletion of Peripheral Blood Pro-Inflammatory Monocytes, Myeloid and Plasmacytoid Dendritic Cells in Patients with Severe COVID-19 Pneumonia. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.627548"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"2352","DOI":"10.1089\/ars.2012.4834","article-title":"CD163 and Inflammation: Biological, Diagnostic, and Therapeutic Aspects","volume":"18","author":"Etzerodt","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/00365513.2011.626868","article-title":"Soluble CD163. Scand","volume":"72","year":"2012","journal-title":"J. Clin. Lab. Investig."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Tsuchiya, K., Suzuki, Y., Yoshimura, K., Yasui, H., Karayama, M., Hozumi, H., Furuhashi, K., Enomoto, N., Fujisawa, T., and Nakamura, Y. (2019). Macrophage Mannose Receptor CD206 Predicts Prognosis in Community-Acquired Pneumonia. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-55289-2"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/ni.1836","article-title":"CD36 Ligands Promote Sterile Inflammation through Assembly of a Toll-like Receptor 4 and 6 Heterodimer","volume":"11","author":"Stewart","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"re3","DOI":"10.1126\/scisignal.272re3","article-title":"CD36, a Scavenger Receptor Involved in Immunity, Metabolism, Angiogenesis, and Behavior","volume":"2","author":"Silverstein","year":"2009","journal-title":"Sci. Signal."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1007\/s11883-012-0228-1","article-title":"Current Concepts of the Role of Oxidized LDL Receptors in Atherosclerosis","volume":"14","author":"Goyal","year":"2012","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"2848","DOI":"10.1182\/bloodadvances.2018025411","article-title":"Platelet CD36 Signaling through ERK5 Promotes Caspase-Dependent Procoagulant Activity and Fibrin Deposition in Vivo","volume":"2","author":"Yang","year":"2018","journal-title":"Blood Adv."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"e200","DOI":"10.1097\/CCM.0000000000000119","article-title":"Trauma-Hemorrhagic Shock Induces a CD36-Dependent RBC Endothelial-Adhesive Phenotype","volume":"42","author":"Deitch","year":"2014","journal-title":"Crit. Care Med."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/S0083-6729(06)74018-3","article-title":"Release of Interleukins and Other Inflammatory Cytokines by Human Adipose Tissue Is Enhanced in Obesity and Primarily Due to the Nonfat Cells","volume":"74","author":"Fain","year":"2006","journal-title":"Vitam Horm."},{"key":"ref_116","first-page":"4","article-title":"Recent Advances in the Relationship between Obesity, Inflammation, and Insulin Resistance","volume":"17","author":"Bastard","year":"2006","journal-title":"Eur. Cytokine Netw."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1016\/j.metabol.2007.06.028","article-title":"Release in Vitro of Adipsin, Vascular Cell Adhesion Molecule 1, Angiotensin 1-Converting Enzyme, and Soluble Tumor Necrosis Factor Receptor 2 by Human Omental Adipose Tissue as Well as by the Nonfat Cells and Adipocytes","volume":"56","author":"Fain","year":"2007","journal-title":"Metabolism"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1111\/joim.12540","article-title":"Adipose Tissue Regulates Insulin Sensitivity: Role of Adipogenesis, de Novo Lipogenesis and Novel Lipids","volume":"280","author":"Smith","year":"2016","journal-title":"J. Intern. Med."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/j.mce.2009.08.018","article-title":"Adipose Tissue as an Endocrine Organ","volume":"316","author":"Galic","year":"2010","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.jhep.2017.11.014","article-title":"Lipotoxicity and the Gut-Liver Axis in NASH Pathogenesis","volume":"68","author":"Marra","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1007\/s11684-013-0262-6","article-title":"Mechanisms of Insulin Resistance in Obesity","volume":"7","author":"Ye","year":"2013","journal-title":"Front. Med."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"21630","DOI":"10.1002\/jcp.28821","article-title":"Impact of Different Ectopic Fat Depots on Cardiovascular and Metabolic Diseases","volume":"234","author":"Ferrara","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"193","DOI":"10.33549\/physiolres.932993","article-title":"Excess of Free Fatty Acids as a Cause of Metabolic Dysfunction in Skeletal Muscle","volume":"65","author":"Tumova","year":"2016","journal-title":"Physiol. Res."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/978-3-319-48382-5_3","article-title":"Eat and Death: Chronic Over-Eating","volume":"960","author":"Engin","year":"2017","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1194\/jlr.E069880","article-title":"Lipotoxicity: Many Roads to Cell Dysfunction and Cell Death: Introduction to a Thematic Review Series","volume":"57","author":"Schaffer","year":"2016","journal-title":"J. Lipid Res."},{"key":"ref_126","first-page":"73","article-title":"Effect of IL-6 Deficiency on Myocardial Expression of Fatty Acid Transporters and Intracellular Lipid Deposits","volume":"58","author":"Chabowski","year":"2007","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1038\/s41419-020-03003-w","article-title":"Understanding Lipotoxicity in NAFLD Pathogenesis: Is CD36 a Key Driver?","volume":"11","author":"Rada","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"H293","DOI":"10.1152\/ajpheart.00520.2017","article-title":"Regulating MicroRNA Expression: At the Heart of Diabetes Mellitus and the Mitochondrion","volume":"314","author":"Hathaway","year":"2018","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"R\u00f6mer, A., Linn, T., and Petry, S.F. (2021). Lipotoxic Impairment of Mitochondrial Function in \u03b2-Cells: A Review. Antioxidants, 10.","DOI":"10.3390\/antiox10020293"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1097\/SHK.0b013e31815abbc6","article-title":"Changes in Plasma Free Fatty Acid Levels in Septic Patients Are Associated with Cardiac Damage and Reduction in Heart Rate Variability","volume":"29","author":"Nogueira","year":"2008","journal-title":"Shock"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"713","DOI":"10.1016\/j.dsx.2020.05.007","article-title":"Role of Oxidized LDL-Induced \u201cTrained Macrophages\u201d in the Pathogenesis of COVID-19 and Benefits of Pioglitazone: A Hypothesis","volume":"14","author":"Erol","year":"2020","journal-title":"Diabetes Metab. Syndr."},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Cho, K.-H., Kim, J.-R., Lee, I.-C., and Kwon, H.-J. (2021). Native High-Density Lipoproteins (HDL) with Higher Paraoxonase Exerts a Potent Antiviral Effect against SARS-CoV-2 (COVID-19), While Glycated HDL Lost the Antiviral Activity. Antioxidants, 10.","DOI":"10.3390\/antiox10020209"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"e140327","DOI":"10.1172\/jci.insight.140327","article-title":"COVID-19 Infection Alters Kynurenine and Fatty Acid Metabolism, Correlating with IL-6 Levels and Renal Status","volume":"5","author":"Thomas","year":"2020","journal-title":"JCI Insight"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.amjms.2020.11.007","article-title":"Hyperglycemia, Insulin, and Insulin Resistance in Sepsis","volume":"361","author":"Rivas","year":"2021","journal-title":"Am. J. Med. Sci."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1097\/MCO.0000000000000253","article-title":"Lipid Metabolism in Critical Illness","volume":"19","author":"Green","year":"2016","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Lee, S.H., Park, M.S., Park, B.H., Jung, W.J., Lee, I.S., Kim, S.Y., Kim, E.Y., Jung, J.Y., Kang, Y.A., and Kim, Y.S. (2015). Prognostic Implications of Serum Lipid Metabolism over Time during Sepsis. BioMed Res. Int., 2015.","DOI":"10.1155\/2015\/789298"},{"key":"ref_137","first-page":"45","article-title":"Changes in Plasma Lipid and In-Hospital Deaths in Patients with Sepsis","volume":"34","author":"Nabavi","year":"2020","journal-title":"Med. J. Islam. Repub. Iran"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.jcrc.2014.04.018","article-title":"Serum Lipid Profile, Cytokine Production, and Clinical Outcome in Patients with Severe Sepsis","volume":"29","author":"Lekkou","year":"2014","journal-title":"J. Crit. Care"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/cc12517","article-title":"Serum Adipocyte Fatty Acid-Binding Protein in the Critically Ill","volume":"17","author":"Das","year":"2013","journal-title":"Crit. Care"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"R22","DOI":"10.1186\/cc12498","article-title":"Serum Adipocyte Fatty Acid-Binding Protein Levels in Patients with Critical Illness Are Associated with Insulin Resistance and Predict Mortality","volume":"17","author":"Huang","year":"2013","journal-title":"Crit. Care"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1038\/nrd2589","article-title":"Fatty Acid-Binding Proteins: Role in Metabolic Diseases and Potential as Drug Targets","volume":"7","author":"Furuhashi","year":"2008","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1016\/j.biochi.2013.08.006","article-title":"Alteration of Plasma Phospholipid Fatty Acid Profile in Patients with Septic Shock","volume":"95","author":"Rival","year":"2013","journal-title":"Biochimie"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1007\/s00134-011-2458-z","article-title":"Dyslipidemia: A Prospective Controlled Randomized Trial of Intensive Glycemic Control in Sepsis","volume":"38","author":"Cappi","year":"2012","journal-title":"Intensive Care Med."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.jcrc.2008.09.002","article-title":"Levels of Oxidized Low-Density Lipoproteins Are Increased in Patients with Severe Sepsis","volume":"23","author":"Behnes","year":"2008","journal-title":"J. Crit. Care"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"3015","DOI":"10.1172\/JCI28898","article-title":"TLR4 Links Innate Immunity and Fatty Acid-Induced Insulin Resistance","volume":"116","author":"Shi","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1002\/hep.23122","article-title":"Toll-like Receptor 4 Is Involved in the Development of Fructose-Induced Hepatic Steatosis in Mice","volume":"50","author":"Spruss","year":"2009","journal-title":"Hepatology"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1038\/nm.2851","article-title":"Fetuin-A Acts as an Endogenous Ligand of TLR4 to Promote Lipid-Induced Insulin Resistance","volume":"18","author":"Pal","year":"2012","journal-title":"Nat. Med."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mce.2015.05.014","article-title":"Fetuin A Promotes Lipotoxicity in \u03b2 Cells through the TLR4 Signaling Pathway and the Role of Pioglitazone in Anti-Lipotoxicity","volume":"412","author":"Shen","year":"2015","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1111\/joim.13144","article-title":"Cytokine Storm Syndrome in Coronavirus Disease 2019: A Narrative Review","volume":"289","author":"Gao","year":"2021","journal-title":"J. Intern. Med."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1182\/blood-2017-06-793141","article-title":"Kinetics and Biomarkers of Severe Cytokine Release Syndrome after CD19 Chimeric Antigen Receptor\u2013Modified T-Cell Therapy","volume":"130","author":"Hay","year":"2017","journal-title":"Blood"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1182\/blood-2014-05-552729","article-title":"Current Concepts in the Diagnosis and Management of Cytokine Release Syndrome","volume":"124","author":"Lee","year":"2014","journal-title":"Blood"},{"key":"ref_152","first-page":"1","article-title":"Cytokine Release Syndrome","volume":"6","author":"Subklewe","year":"2018","journal-title":"J. Immunother. Cancer"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1093\/ajcp\/aqaa124","article-title":"SARS-CoV-2 Infection\u2013Associated Hemophagocytic Lymphohistiocytosis","volume":"154","author":"Prilutskiy","year":"2020","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1097\/BOR.0000000000000093","article-title":"Hyperinflammation, rather than Hemophagocytosis, Is the Common Link between Macrophage Activation Syndrome and Hemophagocytic Lymphohistiocytosis","volume":"26","author":"Weaver","year":"2014","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"119","DOI":"10.3389\/fimmu.2019.00119","article-title":"The Immunology of Macrophage Activation Syndrome","volume":"10","author":"Crayne","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/S0140-6736(20)30628-0","article-title":"COVID-19: Consider Cytokine Storm Syndromes and Immunosuppression","volume":"395","author":"Mehta","year":"2020","journal-title":"Lancet"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s00296-020-04636-y","article-title":"Hemophagocytic Lymphohistiocytosis: A Review Inspired by the COVID-19 Pandemic","volume":"41","author":"Soy","year":"2021","journal-title":"Rheumatol. Int."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1002\/pbc.21039","article-title":"HLH-2004: Diagnostic and Therapeutic Guidelines for Hemophagocytic Lymphohistiocytosis","volume":"48","author":"Henter","year":"2007","journal-title":"Pediatr. Blood Cancer."},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Lorenz, G., Moog, P., Bachmann, Q., La Ros\u00e9e, P., Schneider, H., Schlegl, M., Spinner, C., Heemann, U., Schmid, R.M., and Alg\u00fcl, H. (2020). Title: Cytokine Release Syndrome Is Not Usually Caused by Secondary Hemophagocytic Lymphohistiocytosis in a Cohort of 19 Critically Ill COVID-19 Patients. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-75260-w"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1080\/22221751.2021.1884503","article-title":"COVID-19-Associated Cytokine Storm Syndrome and Diagnostic Principles: An Old and New Issue","volume":"10","author":"Yongzhi","year":"2021","journal-title":"Emerg. Microbes Infect."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.trsl.2021.03.002","article-title":"COVID-19 and Cytokine Storm Syndrome: Are There Lessons from Macrophage Activation Syndrome?","volume":"232","author":"Ombrello","year":"2021","journal-title":"Transl. Res."},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Colafrancesco, S., Alessandri, C., Conti, F., and Priori, R. (2020). COVID-19 Gone Bad: A New Character in the Spectrum of the Hyperferritinemic Syndrome?. Autoimmun. Rev., 19.","DOI":"10.1016\/j.autrev.2020.102573"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1056\/NEJMoa2028836","article-title":"Efficacy of Tocilizumab in Patients Hospitalized with Covid-19","volume":"383","author":"Stone","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_164","unstructured":"(2021). CORIMUNO-19 Collaborative group Effect of Anakinra versus Usual Care in Adults in Hospital with COVID-19 and Mild-to-Moderate Pneumonia (CORIMUNO-ANA-1): A Randomised Controlled Trial. Lancet Respir. Med., 9, 295\u2013304."},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1001\/jamainternmed.2020.6615","article-title":"Effect of Tocilizumab vs Standard Care on Clinical Worsening in Patients Hospitalized with COVID-19 Pneumonia: A Randomized Clinical Trial","volume":"181","author":"Salvarani","year":"2021","journal-title":"JAMA Intern. Med."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"L596","DOI":"10.1136\/jitc-2020-000930","article-title":"The Society for Immunotherapy of Cancer Perspective on Regulation of Interleukin-6 Signaling in COVID-19-Related Systemic Inflammatory Response","volume":"8","author":"Arnaldez","year":"2020","journal-title":"J. Immunother. Cancer"},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1079\/PNS2004378","article-title":"Anti-Cytokine and Anti-Inflammatory Therapies for the Treatment of Severe Sepsis: Progress and Pitfalls","volume":"63","author":"Minnich","year":"2004","journal-title":"Proc. Nutr. Soc."},{"key":"ref_168","first-page":"209","article-title":"Anticytokine therapy in sepsis and why it fails","volume":"14","author":"Kula","year":"2008","journal-title":"Klin. Mikrobiol. Infekc. Lek."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1136\/annrheumdis-2020-218323","article-title":"Temple University COVID-19 Research Group Preliminary Predictive Criteria for COVID-19 Cytokine Storm","volume":"80","author":"Caricchio","year":"2021","journal-title":"Ann. Rheum. Dis."},{"key":"ref_170","doi-asserted-by":"crossref","unstructured":"Wang, C., Xie, J., Zhao, L., Fei, X., Zhang, H., Tan, Y., Nie, X., Zhou, L., Liu, Z., and Ren, Y. (2020). Alveolar Macrophage Dysfunction and Cytokine Storm in the Pathogenesis of Two Severe COVID-19 Patients. EBioMedicine, 57.","DOI":"10.1016\/j.ebiom.2020.102833"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1378\/chest.101.6.1644","article-title":"Definitions for Sepsis and Organ Failure and Guidelines for the Use of Innovative Therapies in Sepsis. The ACCP\/SCCM Consensus Conference Committee. American College of Chest Physicians\/Society of Critical Care Medicine","volume":"101","author":"Bone","year":"1992","journal-title":"Chest"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"E61","DOI":"10.1542\/peds.108.4.e61","article-title":"Reactive Hyperemia and Interleukin 6, Interleukin 8, and Tumor Necrosis Factor-Alpha in the Diagnosis of Early-Onset Neonatal Sepsis","volume":"108","author":"Martin","year":"2001","journal-title":"Pediatrics"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1097\/00000658-199204000-00009","article-title":"Cytokine Serum Level during Severe Sepsis in Human IL-6 as a Marker of Severity","volume":"215","author":"Damas","year":"1992","journal-title":"Ann. Surg."},{"key":"ref_175","doi-asserted-by":"crossref","unstructured":"Molano Franco, D., Arevalo-Rodriguez, I., Roqu\u00e9, I., Figuls, M., Montero Oleas, N.G., Nuvials, X., and Zamora, J. (2019). Plasma Interleukin-6 Concentration for the Diagnosis of Sepsis in Critically Ill Adults. Cochrane Database Syst. Rev., 4.","DOI":"10.1002\/14651858.CD011811.pub2"},{"key":"ref_176","doi-asserted-by":"crossref","unstructured":"Gorham, J., Moreau, A., Corazza, F., Peluso, L., Ponthieux, F., Talamonti, M., Izzi, A., Nagant, C., Ndieugnou Djangang, N., and Garufi, A. (2020). Interleukine-6 in Critically Ill COVID-19 Patients: A Retrospective Analysis. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0244628"},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Hayden, M.R. (2020). Endothelial Activation and Dysfunction in Metabolic Syndrome, Type 2 Diabetes and Coronavirus Disease 2019. J. Int. Med. Res., 48.","DOI":"10.1177\/0300060520939746"},{"key":"ref_178","doi-asserted-by":"crossref","unstructured":"Fosse, J.H., Haraldsen, G., Falk, K., and Edelmann, R. (2021). Endothelial Cells in Emerging Viral Infections. Front. Cardiovasc. Med., 8.","DOI":"10.3389\/fcvm.2021.619690"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.yjmcc.2020.07.003","article-title":"Coagulopathy in COVID-19: Focus on Vascular Thrombotic Events","volume":"146","author":"Shi","year":"2020","journal-title":"J. Mol. Cell. Cardiol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1007\/s11239-020-02134-3","article-title":"COVID-19 Update: Covid-19-Associated Coagulopathy","volume":"50","author":"Becker","year":"2020","journal-title":"J. Thromb. Thrombolysis"},{"key":"ref_181","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_182","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1136\/thoraxjnl-2013-204367","article-title":"Proteinase-Activated Receptors in Fibroproliferative Lung Disease","volume":"69","author":"Williams","year":"2014","journal-title":"Thorax"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"e575","DOI":"10.1016\/S2352-3026(20)30216-7","article-title":"Endotheliopathy in COVID-19-Associated Coagulopathy: Evidence from a Single-Centre, Cross-Sectional Study","volume":"7","author":"Goshua","year":"2020","journal-title":"Lancet Haematol."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"315","DOI":"10.31083\/j.rcm.2020.03.126","article-title":"Endothelial Dysfunction Contributes to COVID-19-Associated Vascular Inflammation and Coagulopathy","volume":"21","author":"Zhang","year":"2020","journal-title":"Rev. Cardiovasc. Med."},{"key":"ref_185","doi-asserted-by":"crossref","unstructured":"Sahai, A., Bhandari, R., Koupenova, M., Freedman, J., Godwin, M., McIntyre, T., Chung, M., Iskandar, J.-P., Kamran, H., and Aggarwal, A. (2020). SARS-CoV-2 Receptors Are Expressed on Human Platelets and the Effect of Aspirin on Clinical Outcomes in COVID-19 Patients. Res. Sq.","DOI":"10.21203\/rs.3.rs-119031\/v1"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.bj.2020.08.007","article-title":"Endothelial Glycocalyx Damage as a Systemic Inflammatory Microvascular Endotheliopathy in COVID-19","volume":"43","year":"2020","journal-title":"Biomed. J."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1093\/cvr\/cvx093","article-title":"The Microcirculation: A Key Player in Obesity-Associated Cardiovascular Disease","volume":"113","author":"Sorop","year":"2017","journal-title":"Cardiovasc. Res."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1042\/CS20150143","article-title":"Inflammation-Induced Microvascular Insulin Resistance Is an Early Event in Diet-Induced Obesity","volume":"129","author":"Zhao","year":"2015","journal-title":"Clin. Sci."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S1016-8478(23)13515-1","article-title":"Octamer Motif Is Required for the NF-KappaB-Mediated Induction of the Inducible Nitric Oxide Synthase Gene Expression in RAW 264.7 Macrophages","volume":"9","author":"Kim","year":"1999","journal-title":"Mol. Cells"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"F932","DOI":"10.1152\/ajprenal.00066.2008","article-title":"Role of NF-KappaB and PI 3-Kinase\/Akt in TNF-Alpha-Induced Cytotoxicity in Microvascular Endothelial Cells","volume":"295","author":"Zhou","year":"2008","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"R125","DOI":"10.1186\/cc6190","article-title":"Discordance between Microvascular Permeability and Leukocyte Dynamics in Septic Inducible Nitric Oxide Synthase Deficient Mice","volume":"11","author":"Hollenberg","year":"2007","journal-title":"Crit. Care"},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.niox.2010.06.002","article-title":"Time Course of Liver Nitric Oxide Concentration in Early Septic Shock by Cecal Ligation and Puncture in Rats","volume":"23","author":"Eyenga","year":"2010","journal-title":"Nitric Oxide"},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"76","DOI":"10.4103\/ijpvm.IJPVM_258_20","article-title":"Hypothesis of COVID-19 Therapy with Sildenafil","volume":"11","author":"Mario","year":"2020","journal-title":"Int. J. Prev. Med."},{"key":"ref_194","unstructured":"Karki, R., Sharma, B.R., Tuladhar, S., Williams, E.P., Zalduondo, L., Samir, P., Zheng, M., Sundaram, B., Banoth, B., and Malireddi, R.K.S. (2020). COVID-19 Cytokines and the Hyperactive Immune Response: Synergism of TNF-\u03b1 and IFN-\u03b3 in Triggering Inflammation, Tissue Damage, and Death. bioRxiv."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1152\/japplphysiol.90495.2008","article-title":"Selective Inhibition of INOS Attenuates Trauma-Hemorrhage\/Resuscitation-Induced Hepatic Injury","volume":"105","author":"Kan","year":"2008","journal-title":"J. Appl. Physiol."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1097\/00024382-200005000-00009","article-title":"Endotoxin-Induced Mesenteric Microvascular Changes Involve INOS-Derived Nitric Oxide: Results from a Study Using INOS Knock out Mice","volume":"13","author":"Suzuki","year":"2000","journal-title":"Shock"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.jss.2004.03.011","article-title":"Selective Inducible Nitric Oxide Synthase (INOS) Inhibition Attenuates Remote Acute Lung Injury in a Model of Ruptured Abdominal Aortic Aneurysm","volume":"120","author":"Harkin","year":"2004","journal-title":"J. Surg. Res."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1111\/wrr.12560","article-title":"Neutrophil Extracellular Traps Coincide with a Pro-Coagulant Status of Microcirculatory Endothelium in Burn Wounds","volume":"25","author":"Korkmaz","year":"2017","journal-title":"Wound Repair Regen."},{"key":"ref_199","doi-asserted-by":"crossref","unstructured":"Sch\u00f6nrich, G., Raftery, M.J., and Samstag, Y. (2020). Devilishly Radical NETwork in COVID-19: Oxidative Stress, Neutrophil Extracellular Traps (NETs), and T Cell Suppression. Adv. Biol. Regul., 77.","DOI":"10.1016\/j.jbior.2020.100741"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"102925","DOI":"10.1016\/j.ebiom.2020.102925","article-title":"Vascular Occlusion by Neutrophil Extracellular Traps in COVID-19","volume":"58","author":"Leppkes","year":"2020","journal-title":"EBioMedicine"},{"key":"ref_201","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_202","doi-asserted-by":"crossref","unstructured":"Barnes, B.J., Adrover, J.M., Baxter-Stoltzfus, A., Borczuk, A., Cools-Lartigue, J., Crawford, J.M., Da\u00dfler-Plenker, J., Guerci, P., Huynh, C., and Knight, J.S. (2020). Targeting Potential Drivers of COVID-19: Neutrophil Extracellular Traps. J. Exp. Med., 217.","DOI":"10.1084\/jem.20200652"},{"key":"ref_203","doi-asserted-by":"crossref","unstructured":"Zuo, Y., Yalavarthi, S., Shi, H., Gockman, K., Zuo, M., Madison, J.A., Blair, C., Weber, A., Barnes, B.J., and Egeblad, M. (2020). Neutrophil Extracellular Traps (NETs) as Markers of Disease Severity in COVID-19. medRxiv.","DOI":"10.1101\/2020.04.09.20059626"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.3389\/fimmu.2019.01320","article-title":"Regulation of Innate Immune Responses by Platelets","volume":"10","author":"Ribeiro","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1160\/TH14-11-0943","article-title":"Aspirin and P2Y12 Inhibitors in Platelet-Mediated Activation of Neutrophils and Monocytes","volume":"114","author":"Schrottmaier","year":"2015","journal-title":"Thromb. Haemost."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1080\/09537104.2018.1430358","article-title":"Measuring and Interpreting Platelet-Leukocyte Aggregates","volume":"29","author":"Finsterbusch","year":"2018","journal-title":"Platelets"},{"key":"ref_207","doi-asserted-by":"crossref","unstructured":"Bhardwaj, A., Sapra, L., Saini, C., Azam, Z., Mishra, P.K., Verma, B., Mishra, G.C., and Srivastava, R.K. (2021). COVID-19: Immunology, Immunopathogenesis and Potential Therapies. Int. Rev. Immunol., 1\u201336.","DOI":"10.1080\/08830185.2021.1883600"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.jaci.2020.05.006","article-title":"Complement Activation in Patients with COVID-19: A Novel Therapeutic Target","volume":"146","author":"Cugno","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.3389\/fphar.2020.01278","article-title":"COVID-19 Usurps Host Regulatory Networks","volume":"11","author":"Curran","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_210","doi-asserted-by":"crossref","unstructured":"Grobler, C., Maphumulo, S.C., Grobbelaar, L.M., Bredenkamp, J.C., Laubscher, G.J., Lourens, P.J., Steenkamp, J., Kell, D.B., and Pretorius, E. (2020). Covid-19: The Rollercoaster of Fibrin(Ogen), D-Dimer, Von Willebrand Factor, P-Selectin and Their Interactions with Endothelial Cells, Platelets and Erythrocytes. Int. J. Mol. Sci., 21.","DOI":"10.20944\/preprints202007.0142.v1"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1093\/cvr\/cvaa230","article-title":"Endothelial Dysfunction in COVID-19: A Position Paper of the ESC Working Group for Atherosclerosis and Vascular Biology, and the ESC Council of Basic Cardiovascular Science","volume":"116","author":"Evans","year":"2020","journal-title":"Cardiovasc. Res."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/S0140-6736(20)30937-5","article-title":"Endothelial Cell Infection and Endotheliitis in COVID-19","volume":"395","author":"Varga","year":"2020","journal-title":"Lancet"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1002\/path.1570","article-title":"Tissue Distribution of ACE2 Protein, the Functional Receptor for SARS Coronavirus. A First Step in Understanding SARS Pathogenesis","volume":"203","author":"Hamming","year":"2004","journal-title":"J. Pathol."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.tcm.2020.10.005","article-title":"COVID-19\u2014A Vascular Disease","volume":"31","author":"Siddiqi","year":"2021","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"e00781","DOI":"10.1128\/mBio.00781-18","article-title":"CD147 Promotes Entry of Pentamer-Expressing Human Cytomegalovirus into Epithelial and Endothelial Cells","volume":"9","author":"Vanarsdall","year":"2018","journal-title":"mBio"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1186\/s13054-020-03062-7","article-title":"The Vascular Endothelium: The Cornerstone of Organ Dysfunction in Severe SARS-CoV-2 Infection","volume":"24","author":"Pons","year":"2020","journal-title":"Crit. Care"},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"2404","DOI":"10.1161\/ATVBAHA.120.314860","article-title":"Endothelial Dysfunction and Thrombosis in Patients With COVID-19-Brief Report","volume":"40","author":"Nagashima","year":"2020","journal-title":"Arterioscler. Thromb. Vasc Biol."},{"key":"ref_218","doi-asserted-by":"crossref","unstructured":"Wazny, V., Siau, A., Wu, K.X., and Cheung, C. (2020). Vascular Underpinning of COVID-19. Open Biol., 10.","DOI":"10.1098\/rsob.200208"},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1161\/CIRCULATIONAHA.120.050354","article-title":"Severe COVID-19 Is a Microvascular Disease","volume":"142","author":"Lowenstein","year":"2020","journal-title":"Circulation"},{"key":"ref_220","doi-asserted-by":"crossref","unstructured":"Barbosa, L.C., Gon\u00e7alves, T.L., de Araujo, L.P., and Rosario, L.V. (2021). de O.; Ferrer, V.P. Endothelial Cells and SARS-CoV-2: An Intimate Relationship. Vascul. Pharmacol., 137.","DOI":"10.1016\/j.vph.2021.106829"},{"key":"ref_221","first-page":"718","article-title":"The Stress Concept","volume":"115","author":"Selye","year":"1976","journal-title":"Can. Med. Assoc. J."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/S2213-8587(20)30216-3","article-title":"Association between High Serum Total Cortisol Concentrations and Mortality from COVID-19","volume":"8","author":"Tan","year":"2020","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1007\/s12020-020-02325-1","article-title":"COVID-19, Hypothalamo-Pituitary-Adrenal Axis and Clinical Implications","volume":"68","author":"Pal","year":"2020","journal-title":"Endocrine"},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"179","DOI":"10.32598\/bcn.11.covid19.1168.2","article-title":"The Role of Anxiety and Cortisol in Outcomes of Patients with Covid-19","volume":"11","author":"Ramezani","year":"2020","journal-title":"Basic Clin. Neurosci."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.eprac.2020.10.014","article-title":"The Impact of COVID-19 Viral Infection on the Hypothalamic-Pituitary-Adrenal Axis","volume":"27","author":"Alzahrani","year":"2021","journal-title":"Endocr. Pract."},{"key":"ref_226","doi-asserted-by":"crossref","unstructured":"Mao, Y., Xu, B., Guan, W., Xu, D., Li, F., Ren, R., Zhu, X., Gao, Y., and Jiang, L. (2020). The Adrenal Cortex, an Underestimated Site of SARS-CoV-2 Infection. Front. Endocrinol., 11.","DOI":"10.3389\/fendo.2020.593179"},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/S0140-6736(20)30317-2","article-title":"Clinical Evidence Does Not Support Corticosteroid Treatment for 2019-NCoV Lung Injury","volume":"395","author":"Russell","year":"2020","journal-title":"Lancet"},{"key":"ref_228","doi-asserted-by":"crossref","unstructured":"Granger, D.N., and Senchenkova, E. (2010). Inflammation and the Microcirculation; Integrated Systems Physiology\u2014From Cell to Function, Morgan & Claypool Life Sciences.","DOI":"10.4199\/C00013ED1V01Y201006ISP008"},{"key":"ref_229","unstructured":"Majno, G., and Joris, I. (2004). Cells, Tissues and Disease: Principles of General Pathology, Oxford University Press."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"11685","DOI":"10.1074\/jbc.REV119.005593","article-title":"Trouble Is Coming: Signaling Pathways That Regulate General Stress Responses in Bacteria","volume":"294","author":"Gottesman","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1039\/C8MO00283E","article-title":"Small Open Reading Frames and Cellular Stress Responses","volume":"15","author":"Khitun","year":"2019","journal-title":"Mol. Omics"},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.freeradbiomed.2012.11.010","article-title":"Aldehyde Dehydrogenases in Cellular Responses to Oxidative\/Electrophilic Stress","volume":"56","author":"Singh","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"96","DOI":"10.4161\/rna.22638","article-title":"RNA Helicases: Diverse Roles in Prokaryotic Response to Abiotic Stress","volume":"10","author":"Owttrim","year":"2013","journal-title":"RNA Biol."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"3425","DOI":"10.1529\/biophysj.106.090084","article-title":"Mathematical Models of Specificity in Cell Signaling","volume":"92","author":"Bardwell","year":"2007","journal-title":"Biophys. J."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1101\/sqb.2000.65.127","article-title":"Repair of Endogenous DNA Damage","volume":"65","author":"Lindahl","year":"2000","journal-title":"Cold Spring Harb. Symp. Quant. Biol."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"3485","DOI":"10.1128\/MCB.19.5.3485","article-title":"Transcriptional Cross Talk between NF-KappaB and P53","volume":"19","author":"Webster","year":"1999","journal-title":"Mol. Cell. Biol."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jbior.2015.09.009","article-title":"Reciprocal Regulation of P53 and NF-\u039aB by Diacylglycerol Kinase \u03b6","volume":"60","author":"Tanaka","year":"2016","journal-title":"Adv. Biol. Regul."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"23","DOI":"10.3389\/fcell.2018.00023","article-title":"Microenvironment-Cell Nucleus Relationship in the Context of Oxidative Stress","volume":"6","author":"Chittiboyina","year":"2018","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.abb.2016.08.005","article-title":"Keap1, the Cysteine-Based Mammalian Intracellular Sensor for Electrophiles and Oxidants","volume":"617","author":"Kostov","year":"2017","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"64","DOI":"10.3389\/fonc.2014.00064","article-title":"Targeting PI3K\/Akt\/MTOR Signaling in Cancer","volume":"4","author":"Porta","year":"2014","journal-title":"Front. Oncol."},{"key":"ref_241","doi-asserted-by":"crossref","unstructured":"Owonikoko, T.K., and Khuri, F.R. (2013). Targeting the PI3K\/AKT\/MTOR Pathway: Biomarkers of Success and Tribulation. Am. Soc. Clin. Oncol. Educ. Book.","DOI":"10.1200\/EdBook_AM.2013.33.e395"},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.pneurobio.2010.10.007","article-title":"Energy Metabolism in Adult Neural Stem Cell Fate","volume":"93","author":"Rafalski","year":"2011","journal-title":"Prog. Neurobiol."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1248\/bpb.b17-00724","article-title":"AMPK-Mediated Regulation of Lipid Metabolism by Phosphorylation","volume":"41","author":"Wang","year":"2018","journal-title":"Biol. Pharm. Bull."},{"key":"ref_244","first-page":"332","article-title":"The Mechanistic Target of Rapamycin (MTOR): Novel Considerations as an Antiviral Treatment","volume":"17","author":"Maiese","year":"2020","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_245","doi-asserted-by":"crossref","unstructured":"Pietzner, M., Kaul, A., Henning, A.-K., Kastenm\u00fcller, G., Artati, A., Lerch, M.M., Adamski, J., Nauck, M., and Friedrich, N. (2017). Comprehensive Metabolic Profiling of Chronic Low-Grade Inflammation among Generally Healthy Individuals. BMC Med., 15.","DOI":"10.1186\/s12916-017-0974-6"},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1038\/mi.2017.19","article-title":"Inflammasomes and Intestinal Inflammation","volume":"10","author":"Zmora","year":"2017","journal-title":"Mucosal Immunol."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"e12555","DOI":"10.1111\/cpr.12555","article-title":"The Protective Roles of NLRP6 in Intestinal Epithelial Cells","volume":"52","author":"Yin","year":"2019","journal-title":"Cell Prolif."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1002\/cphy.c120033","article-title":"Muscle as a Secretory Organ","volume":"3","author":"Pedersen","year":"2013","journal-title":"Compr. Physiol."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1152\/physrev.90100.2007","article-title":"Muscle as an Endocrine Organ: Focus on Muscle-Derived Interleukin-6","volume":"88","author":"Pedersen","year":"2008","journal-title":"Physiol. Rev."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.2174\/1381612824666180327165604","article-title":"Signaling Pathways in Inflammation and Anti-Inflammatory Therapies","volume":"24","author":"Yeung","year":"2018","journal-title":"Curr. Pharm. Des."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1093\/intimm\/dxr078","article-title":"Transcriptional Control of T-Cell Development","volume":"23","author":"Naito","year":"2011","journal-title":"Int. Immunol."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/nri3814","article-title":"Germinal Centres and B Cell Lymphomagenesis","volume":"15","author":"Basso","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1038\/mp.2015.67","article-title":"Childhood Trauma and Adulthood Inflammation: A Meta-Analysis of Peripheral C-Reactive Protein, Interleukin-6 and Tumour Necrosis Factor-\u03b1","volume":"21","author":"Baumeister","year":"2016","journal-title":"Mol. Psychiatry"},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.2174\/138161208784246153","article-title":"Adipose Tissue Macrophages, Low Grade Inflammation and Insulin Resistance in Human Obesity","volume":"14","author":"Heilbronn","year":"2008","journal-title":"Curr. Pharm. Des."},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.2147\/DMSO.S302621","article-title":"DPP-4 Inhibitors Have Different Effects on Endothelial Low-Grade Inflammation and on the M1-M2 Macrophage Polarization Under Hyperglycemic Conditions","volume":"14","author":"Prattichizzo","year":"2021","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1007\/s00059-007-3073-1","article-title":"Endothelial Dysfunction as an Early Sign of Atherosclerosis","volume":"32","author":"Giannotti","year":"2007","journal-title":"Herz"},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1113\/expphysiol.2008.043356","article-title":"The Ageing Endothelium, Cardiovascular Risk and Disease in Man","volume":"94","author":"Versari","year":"2009","journal-title":"Exp. Physiol."},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1042\/CS20080069","article-title":"End-Organ Dysfunction and Cardiovascular Outcomes: The Role of the Microcirculation","volume":"116","author":"Lockhart","year":"2009","journal-title":"Clin. Sci."},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1042\/CS20200279","article-title":"Microvascular Disease in Chronic Kidney Disease: The Base of the Iceberg in Cardiovascular Comorbidity","volume":"134","author":"Querfeld","year":"2020","journal-title":"Clin. Sci."},{"key":"ref_260","doi-asserted-by":"crossref","unstructured":"Yamanouchi, M., Mori, M., Hoshino, J., Kinowaki, K., Fujii, T., Ohashi, K., Furuichi, K., Wada, T., and Ubara, Y. (2019). Retinopathy Progression and the Risk of End-Stage Kidney Disease: Results from a Longitudinal Japanese Cohort of 232 Patients with Type 2 Diabetes and Biopsy-Proven Diabetic Kidney Disease. BMJ Open Diabetes Res. Care, 7.","DOI":"10.1136\/bmjdrc-2019-000726"},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/978-981-13-8871-2_4","article-title":"A Glimpse of the Mechanisms Related to Renal Fibrosis in Diabetic Nephropathy","volume":"1165","author":"Zeng","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"424","DOI":"10.2174\/1566523218666180214100351","article-title":"Role of Immune Cells in Diabetic Kidney Disease","volume":"17","author":"Yang","year":"2017","journal-title":"Curr. Gene Ther."},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"2263","DOI":"10.1001\/jama.2015.5370","article-title":"Nonalcoholic Fatty Liver Disease: A Systematic Review","volume":"313","author":"Rinella","year":"2015","journal-title":"JAMA"},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1001\/jama.2020.2298","article-title":"Nonalcoholic Steatohepatitis: A Review","volume":"323","author":"Sheka","year":"2020","journal-title":"JAMA"},{"key":"ref_265","first-page":"603","article-title":"Nonalcoholic Fatty Liver Disease: Common Questions and Answers on Diagnosis and Management","volume":"102","author":"Westfall","year":"2020","journal-title":"Am. Fam. Physician"},{"key":"ref_266","doi-asserted-by":"crossref","unstructured":"Abbate, M., Mascar\u00f3, C.M., Montemayor, S., Casares, M., G\u00f3mez, C., Ugarriza, L., Tejada, S., Abete, I., Zulet, M.A., and Sureda, A. (2021). Non-Alcoholic Fatty Liver Disease Is Associated with Kidney Glomerular Hyperfiltration in Adults with Metabolic Syndrome. J. Clin. Med., 10.","DOI":"10.3390\/jcm10081717"},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1038\/s41577-020-0407-1","article-title":"Tissue Damage from Neutrophil-Induced Oxidative Stress in COVID-19","volume":"20","author":"Laforge","year":"2020","journal-title":"Nat. Rev. Immunol."},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1007\/s10930-020-09935-8","article-title":"Role of Oxidative Stress on SARS-CoV (SARS) and SARS-CoV-2 (COVID-19) Infection: A Review","volume":"39","author":"Suhail","year":"2020","journal-title":"Protein J."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"3038","DOI":"10.1093\/eurheartj\/ehaa623","article-title":"COVID-19 Is, in the End, an Endothelial Disease","volume":"41","author":"Libby","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_270","doi-asserted-by":"crossref","unstructured":"Beltr\u00e1n-Garc\u00eda, J., Osca-Verdegal, R., Pallard\u00f3, F.V., Ferreres, J., Rodr\u00edguez, M., Mulet, S., Sanchis-Gomar, F., Carbonell, N., and Garc\u00eda-Gim\u00e9nez, J.L. (2020). Oxidative Stress and Inflammation in COVID-19-Associated Sepsis: The Potential Role of Anti-Oxidant Therapy in Avoiding Disease Progression. Antioxidants, 9.","DOI":"10.3390\/antiox9100936"},{"key":"ref_271","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1007\/s00011-020-01389-z","article-title":"Coronavirus (Covid-19) Sepsis: Revisiting Mitochondrial Dysfunction in Pathogenesis, Aging, Inflammation, and Mortality","volume":"69","author":"Shenoy","year":"2020","journal-title":"Inflamm. Res."},{"key":"ref_272","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1097\/CCO.0000000000000713","article-title":"Viral Strategies for Circumventing P53: The Case of Severe Acute Respiratory Syndrome Coronavirus","volume":"33","author":"Cardozo","year":"2021","journal-title":"Curr. Opin. Oncol."},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1038\/nrd2755","article-title":"Cell Death and Endoplasmic Reticulum Stress: Disease Relevance and Therapeutic Opportunities","volume":"7","author":"Kim","year":"2008","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_274","doi-asserted-by":"crossref","unstructured":"Banerjee, A., Czinn, S.J., Reiter, R.J., and Blanchard, T.G. (2020). Crosstalk between Endoplasmic Reticulum Stress and Anti-Viral Activities: A Novel Therapeutic Target for COVID-19. Life Sci., 255.","DOI":"10.1016\/j.lfs.2020.117842"},{"key":"ref_275","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/s12575-021-00145-9","article-title":"Effects of Cell Proteostasis Network on the Survival of SARS-CoV-2","volume":"23","author":"Khomari","year":"2021","journal-title":"Biol. Proced. Online"},{"key":"ref_276","doi-asserted-by":"crossref","first-page":"192","DOI":"10.2174\/1389203721666201111160925","article-title":"Are Hsp90 Inhibitors Good Candidates against Covid-19?","volume":"22","author":"Ramos","year":"2020","journal-title":"Curr. Protein Pept. Sci"},{"key":"ref_277","doi-asserted-by":"crossref","first-page":"L444","DOI":"10.1152\/ajplung.00252.2020","article-title":"SARS-CoV-2 May Regulate Cellular Responses through Depletion of Specific Host MiRNAs","volume":"319","author":"Bartoszewski","year":"2020","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"L405","DOI":"10.1152\/ajplung.00457.2020","article-title":"da S.; Azevedo, M.L.V.; Vaz de Paula, C.B.; Nagashima, S.; Machado-Souza, C.; Miggiolaro, A.F.R.D.S.; Baena, C.P.; de Noronha, L.; et al. Deregulated MiRNA Expression Is Associated with Endothelial Dysfunction in Post-Mortem Lung Biopsies of COVID-19 Patients","volume":"320","author":"Centa","year":"2020","journal-title":"Am. J. Physiol. Lung Cell. Mol. Physiol."},{"key":"ref_279","doi-asserted-by":"crossref","unstructured":"Randhawa, P.K., Scanlon, K., Rappaport, J., and Gupta, M.K. (2020). Modulation of Autophagy by SARS-CoV-2: A Potential Threat for Cardiovascular System. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.611275"},{"key":"ref_280","doi-asserted-by":"crossref","unstructured":"Gorshkov, K., Chen, C.Z., Bostwick, R., Rasmussen, L., Xu, M., Pradhan, M., Tran, B.N., Zhu, W., Shamim, K., and Huang, W. (2020). The SARS-CoV-2 Cytopathic Effect Is Blocked with Autophagy Modulators. bioRxiv.","DOI":"10.1101\/2020.05.16.091520"},{"key":"ref_281","doi-asserted-by":"crossref","first-page":"e24","DOI":"10.1016\/j.jinf.2020.03.058","article-title":"Evolutionary Analysis of SARS-CoV-2: How Mutation of Non-Structural Protein 6 (NSP6) Could Affect Viral Autophagy","volume":"81","author":"Benvenuto","year":"2020","journal-title":"J. Infect."},{"key":"ref_282","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1080\/21505594.2020.1780088","article-title":"Autophagy and SARS-CoV-2 Infection: A possible Smart Targeting of the Autophagy Pathway","volume":"11","author":"Shojaei","year":"2020","journal-title":"Virulence"},{"key":"ref_283","doi-asserted-by":"crossref","first-page":"e20201707","DOI":"10.1084\/jem.20201707","article-title":"Inflammasomes Are Activated in Response to SARS-CoV-2 Infection and Are Associated with COVID-19 Severity in Patients","volume":"218","author":"Rodrigues","year":"2021","journal-title":"J. Exp. Med."},{"key":"ref_284","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/s41420-021-00428-w","article-title":"SARS-CoV-2 Engages Inflammasome and Pyroptosis in Human Primary Monocytes","volume":"7","author":"Ferreira","year":"2021","journal-title":"Cell Death Discov."},{"key":"ref_285","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.3389\/fimmu.2020.01518","article-title":"Targeting the NLRP3 Inflammasome in Severe COVID-19","volume":"11","author":"Freeman","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_286","doi-asserted-by":"crossref","first-page":"453","DOI":"10.2147\/RMHP.S284557","article-title":"Impact of COVID-19 Pandemic on Healthcare Professionals and Oral Care Operational Services: A Systemic Review","volume":"14","author":"Bordea","year":"2021","journal-title":"Risk Manag. Healthc. Policy"},{"key":"ref_287","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1016\/j.crad.2020.07.019","article-title":"Thromboembolic Complications of COVID-19: The Combined Effect of a pro-Coagulant Pattern and an Endothelial Thrombo-Inflammatory Syndrome","volume":"75","author":"Vernuccio","year":"2020","journal-title":"Clin. Radiol."},{"key":"ref_288","first-page":"95","article-title":"Microvascular COVID-19 Lung Vessels Obstructive Thromboinflammatory Syndrome (MicroCLOTS): An Atypical Acute Respiratory Distress Syndrome Working Hypothesis","volume":"22","author":"Ciceri","year":"2020","journal-title":"Crit. Care Resusc."},{"key":"ref_289","doi-asserted-by":"crossref","unstructured":"Blaschke, T., and Bajorath, J. (2021). Fine-Tuning of a Generative Neural Network for Designing Multi-Target Compounds. J. Comput. Aided Mol. Des., 1\u20139.","DOI":"10.1007\/s10822-021-00392-8"},{"key":"ref_290","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s40169-017-0181-2","article-title":"A Perspective on Multi-Target Drug Discovery and Design for Complex Diseases","volume":"7","author":"Ramsay","year":"2018","journal-title":"Clin. Transl. Med."},{"key":"ref_291","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1038\/nrd2199","article-title":"How Many Drug Targets Are There?","volume":"5","author":"Overington","year":"2006","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_292","doi-asserted-by":"crossref","first-page":"13","DOI":"10.2147\/JIR.S282213","article-title":"Understanding COVID-19 Pandemic: Molecular Mechanisms and Potential Therapeutic Strategies. An Evidence-Based Review","volume":"14","author":"Hanna","year":"2021","journal-title":"J. Inflamm. Res."},{"key":"ref_293","doi-asserted-by":"crossref","unstructured":"Sarapultsev, A.P., Vassiliev, P.M., Sarapultsev, P.A., Chupakhin, O.N., Ianalieva, L.R., and Sidorova, L.P. (2018). Immunomodulatory Action of Substituted 1,3,4-Thiadiazines on the Course of Myocardial Infarction. Molecules, 23.","DOI":"10.3390\/molecules23071611"},{"key":"ref_294","doi-asserted-by":"crossref","first-page":"FDD44","DOI":"10.4155\/fdd-2020-0014","article-title":"Compounds with Multitarget Activity: Structure-Based Analysis and Machine Learning","volume":"2","author":"Feldmann","year":"2020","journal-title":"Future Drug Discov."},{"key":"ref_295","doi-asserted-by":"crossref","unstructured":"Yumura, M., Nagano, T., and Nishimura, Y. (2020). Novel Multitarget Therapies for Lung Cancer and Respiratory Disease. Molecules, 25.","DOI":"10.3390\/molecules25173987"},{"key":"ref_296","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ijbiomac.2020.05.184","article-title":"High Throughput Virtual Screening Reveals SARS-CoV-2 Multi-Target Binding Natural Compounds to Lead Instant Therapy for COVID-19 Treatment","volume":"160","author":"Naik","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_297","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-Cort\u00e9s, A., Guevara-Ram\u00edrez, P., Kyriakidis, N.C., Barba-Ostria, C., Le\u00f3n C\u00e1ceres, \u00c1., Guerrero, S., Ortiz-Prado, E., Munteanu, C.R., Tejera, E., and Cevallos-Robalino, D. (2021). In Silico Analyses of Immune System Protein Interactome Network, Single-Cell RNA Sequencing of Human Tissues, and Artificial Neural Networks Reveal Potential Therapeutic Targets for Drug Repurposing Against COVID-19. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.598925"},{"key":"ref_298","doi-asserted-by":"crossref","first-page":"24","DOI":"10.4103\/2225-4110.124335","article-title":"Antiviral Natural Products and Herbal Medicines","volume":"4","author":"Lin","year":"2014","journal-title":"J. Tradit. Complement. Med."},{"key":"ref_299","doi-asserted-by":"crossref","unstructured":"Gurung, A.B., Ali, M.A., Lee, J., Farah, M.A., and Al-Anazi, K.M. (2020). Unravelling Lead Antiviral Phytochemicals for the Inhibition of SARS-CoV-2 Mpro Enzyme through in Silico Approach. Life Sci., 255.","DOI":"10.1016\/j.lfs.2020.117831"},{"key":"ref_300","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1142\/S0192415X20500512","article-title":"Potential Targets for Treatment of Coronavirus Disease 2019 (COVID-19): A Review of Qing-Fei-Pai-Du-Tang and Its Major Herbs","volume":"48","author":"Zhong","year":"2020","journal-title":"Am. J. Chin. Med."},{"key":"ref_301","doi-asserted-by":"crossref","unstructured":"Borse, S., Joshi, M., Saggam, A., Bhat, V., Walia, S., Marathe, A., Sagar, S., Chavan-Gautam, P., Girme, A., and Hingorani, L. (2021). Ayurveda Botanicals in COVID-19 Management: An in Silico Multi-Target Approach. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0248479"},{"key":"ref_302","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.fitote.2013.10.010","article-title":"Synergy Effects of Herb Extracts: Pharmacokinetics and Pharmacodynamic Basis","volume":"92","author":"Yang","year":"2014","journal-title":"Fitoterapia"},{"key":"ref_303","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1007\/s11655-020-3476-x","article-title":"In Silico Screening of Potential Chinese Herbal Medicine Against COVID-19 by Targeting SARS-CoV-2 3CLpro and Angiotensin Converting Enzyme II Using Molecular Docking","volume":"26","author":"Gao","year":"2020","journal-title":"Chin. J. Integr. Med."},{"key":"ref_304","first-page":"3099","article-title":"Discovery of Potential Multi-Target-Directed Ligands by Targeting Host-Specific SARS-CoV-2 Structurally Conserved Main Protease","volume":"39","author":"Joshi","year":"2021","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_305","doi-asserted-by":"crossref","first-page":"153401","DOI":"10.1016\/j.phymed.2020.153401","article-title":"Network Pharmacology, Molecular Docking Integrated Surface Plasmon Resonance Technology Reveals the Mechanism of Toujie Quwen Granules against Coronavirus Disease 2019 Pneumonia","volume":"85","author":"Ye","year":"2021","journal-title":"Phytomedicine"},{"key":"ref_306","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1080\/03639045.2020.1788070","article-title":"Network Pharmacology and Molecular Docking Analysis on Molecular Targets and Mechanisms of Huashi Baidu Formula in the Treatment of COVID-19","volume":"46","author":"Tao","year":"2020","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_307","doi-asserted-by":"crossref","unstructured":"de Oliveira, P.G., Termini, L., Durigon, E.L., Lepique, A.P., Sposito, A.C., and Boccardo, E. (2020). Diacerein: A Potential Multi-Target Therapeutic Drug for COVID-19. Med. Hypotheses, 144.","DOI":"10.1016\/j.mehy.2020.109920"},{"key":"ref_308","doi-asserted-by":"crossref","unstructured":"Shree, P., Mishra, P., Selvaraj, C., Singh, S.K., Chaube, R., Garg, N., and Tripathi, Y.B. (2020). Targeting COVID-19 (SARS-CoV-2) Main Protease through Active Phytochemicals of Ayurvedic Medicinal Plants\u2014Withania Somnifera (Ashwagandha), Tinospora Cordifolia (Giloy) and Ocimum Sanctum (Tulsi)\u2014A Molecular Docking Study. J. Biomol. Struct. Dyn., 1\u201314.","DOI":"10.1080\/07391102.2020.1810778"},{"key":"ref_309","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1039\/D0NJ03708G","article-title":"Two Antioxidant 2,5-Disubstituted-1,3,4-Oxadiazoles (CoViTris2020 and ChloViD2020): Successful Repurposing against COVID-19 as the First Potent Multitarget Anti-SARS-CoV-2 Drugs","volume":"45","author":"Rabie","year":"2021","journal-title":"New J. Chem."},{"key":"ref_310","doi-asserted-by":"crossref","unstructured":"Di Micco, S., Musella, S., Scala, M.C., Sala, M., Campiglia, P., Bifulco, G., and Fasano, A. (2020). In Silico Analysis Revealed Potential Anti-SARS-CoV-2 Main Protease Activity by the Zonulin Inhibitor Larazotide Acetate. Front. Chem., 8.","DOI":"10.3389\/fchem.2020.628609"},{"key":"ref_311","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1080\/17512433.2021.1874348","article-title":"SARS-CoV-2 Protein Drug Targets Landscape: A Potential Pharmacological Insight View for the New Drug Development","volume":"14","author":"Chakraborty","year":"2021","journal-title":"Expert Rev. Clin. Pharmacol."},{"key":"ref_312","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1007\/s12015-021-10122-0","article-title":"Mesenchymal Stem Cell-Derived Extracellular Vesicles Carrying MiRNA as a Potential Multi Target Therapy to COVID-19: An in Silico Analysis","volume":"17","author":"Schultz","year":"2021","journal-title":"Stem Cell Rev. Rep."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/14\/7582\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:31:02Z","timestamp":1760164262000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/14\/7582"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,15]]},"references-count":312,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["ijms22147582"],"URL":"https:\/\/doi.org\/10.3390\/ijms22147582","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,15]]}}}