{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T22:12:05Z","timestamp":1791756725372,"version":"4.3.4"},"reference-count":183,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T00:00:00Z","timestamp":1619654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a severe pandemic of the current century. The vicious tentacles of the disease have been disseminated worldwide with unknown complications and repercussions. Advanced COVID-19 syndrome is characterized by the uncontrolled and elevated release of pro-inflammatory cytokines and suppressed immunity, leading to the cytokine storm. The uncontrolled and dysregulated secretion of inflammatory and pro-inflammatory cytokines is positively associated with the severity of the viral infection and mortality rate. The secretion of various pro-inflammatory cytokines such as TNF-\u03b1, IL-1, and IL-6 leads to a hyperinflammatory response by recruiting macrophages, T and B cells in the lung alveolar cells. Moreover, it has been hypothesized that immune cells such as macrophages recruit inflammatory monocytes in the alveolar cells and allow the production of large amounts of cytokines in the alveoli, leading to a hyperinflammatory response in severely ill patients with COVID-19. This cascade of events may lead to multiple organ failure, acute respiratory distress, or pneumonia. Although the disease has a higher survival rate than other chronic diseases, the incidence of complications in the geriatric population are considerably high, with more systemic complications. This review sheds light on the pivotal roles played by various inflammatory markers in COVID-19-related complications. Different molecular pathways, such as the activation of JAK and JAK\/STAT signaling are crucial in the progression of cytokine storm; hence, various mechanisms, immunological pathways, and functions of cytokines and other inflammatory markers have been discussed. A thorough understanding of cytokines\u2019 molecular pathways and their activation procedures will add more insight into understanding immunopathology and designing appropriate drugs, therapies, and control measures to counter COVID-19. Recently, anti-inflammatory drugs and several antiviral drugs have been reported as effective therapeutic drug candidates to control hypercytokinemia or cytokine storm. Hence, the present review also discussed prospective anti-inflammatory and relevant immunomodulatory drugs currently in various trial phases and their possible implications.<\/jats:p>","DOI":"10.3390\/vaccines9050436","type":"journal-article","created":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T04:30:11Z","timestamp":1619670611000},"page":"436","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":216,"title":["Role of Inflammatory Cytokines in COVID-19 Patients: A Review on Molecular Mechanisms, Immune Functions, Immunopathology and Immunomodulatory Drugs to Counter Cytokine Storm"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6774-9847","authenticated-orcid":false,"given":"Ali A.","family":"Rabaan","sequence":"first","affiliation":[{"name":"Molecular Diagnostic Laboratory, Johns Hopkins Aramco Healthcare, Dhahran 31311, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shamsah H.","family":"Al-Ahmed","sequence":"additional","affiliation":[{"name":"Specialty Paediatric Medicine, Qatif Central Hospital, Qatif 32654, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javed","family":"Muhammad","sequence":"additional","affiliation":[{"name":"Department of Microbiology, The University of Haripur, Khyber Pakhtunkhwa 22620, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amjad","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Public Health\/Nutrition, The University of Haripur, Khyber Pakhtunkhwa 22620, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5931-3381","authenticated-orcid":false,"given":"Anupam A","family":"Sule","sequence":"additional","affiliation":[{"name":"Medical Director of Informatics and Outcomes, St Joseph Mercy Oakland, Pontiac, MI 48341, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raghavendra","family":"Tirupathi","sequence":"additional","affiliation":[{"name":"Department of Medicine Keystone Health, Penn State University School of Medicine, Hershey, PA 16801, USA"},{"name":"Department of Medicine, Wellspan Chambersburg and Waynesboro (Pa.) Hospitals, Chambersburg, PA 16801, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abbas Al","family":"Mutair","sequence":"additional","affiliation":[{"name":"Research Center, Almoosa Specialist Hospital, Alahsa 36342, Saudi Arabia"},{"name":"College of Nursing, Prince Nora University, Riyadh 11564, Saudi Arabia"},{"name":"School of Nursing, Wollongong University, Wollongong, NSW 2522, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4552-4513","authenticated-orcid":false,"given":"Saad","family":"Alhumaid","sequence":"additional","affiliation":[{"name":"Administration of Pharmaceutical Care, Ministry of Health, Alahsa 31982, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Awad","family":"Al-Omari","sequence":"additional","affiliation":[{"name":"College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia"},{"name":"Dr. Sulaiman Al-Habib Medical Group, Critical Care and Infection Control Department, Research Centre, Riyadh 11372, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7783-7138","authenticated-orcid":false,"given":"Manish","family":"Dhawan","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Punjab Agricultural University, Ludhiana 141027, Punjab, India"},{"name":"The Trafford Group of Colleges, Manchester WA14 5PQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7763-5547","authenticated-orcid":false,"given":"Ruchi","family":"Tiwari","sequence":"additional","affiliation":[{"name":"Department of Veterinary Microbiology and Immunology, College of Veterinary Sciences, Uttar Pradesh; Pandit DeenDayal Upadhyaya PashuChikitsa Vigyan Vishwavidyalaya Evam Go AnusandhaSansthan (DUVASU), Mathura 281001, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1040-3746","authenticated-orcid":false,"given":"Khan","family":"Sharun","sequence":"additional","affiliation":[{"name":"Division of Surgery, ICAR-Indian Veterinary Research Institute, Mathura 281001, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7623-3343","authenticated-orcid":false,"given":"Ranjan K.","family":"Mohapatra","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Government College of Engineering, Keonjhar 758002, Odisha, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9502-0252","authenticated-orcid":false,"given":"Saikat","family":"Mitra","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka 1000, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5388-3183","authenticated-orcid":false,"given":"Muhammad","family":"Bilal","sequence":"additional","affiliation":[{"name":"School of Life Science and Food Engineering, Huaiyin Institute of Technology, Huaian 223003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salem A.","family":"Alyami","sequence":"additional","affiliation":[{"name":"Department of Mathematics and Statistics, Imam Mohammad Ibn Saud Islamic University, Riyadh 11432, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3188-2272","authenticated-orcid":false,"given":"Talha Bin","family":"Emran","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, BGC Trust University Bangladesh, Chittagong 4381, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0756-1006","authenticated-orcid":false,"given":"Mohammad Ali","family":"Moni","sequence":"additional","affiliation":[{"name":"WHO Collaborating Centre on eHealth, UNSW Digital Health, School of Public Health and Community Medicine, Faculty of Medicine, UNSW Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7469-4752","authenticated-orcid":false,"given":"Kuldeep","family":"Dhama","sequence":"additional","affiliation":[{"name":"Division of Pathology, ICAR-Indian Veterinary Research Institute, Izatnagar, Bareilly 243122, Uttar Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Dhama, K., Khan, S., Tiwari, R., Sircar, S., Bhat, S., Malik, Y.S., Singh, K.P., Chaicumpa, W., Bonilla-Aldana, D.K., and Rodriguez-Morales, A.J. (2020). Coronavirus Disease 2019\u2013COVID-19. Clin. Microbiol. Rev., 33.","DOI":"10.1128\/CMR.00028-20"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Dhama, K., Patel, S.K., Pathak, M., Yatoo, M.I., Tiwari, R., Malik, Y.S., Singh, R., Sah, R., Rabaan, A.A., and Bonilla-Aldana, D.K. (2020). An update on SARS-CoV-2\/COVID-19 with particular reference to its clinical pathology, pathogenesis, immunopathology and mitigation strategies. Travel Med. Infect. Dis., 37.","DOI":"10.1016\/j.tmaid.2020.101755"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1414","DOI":"10.1111\/tbed.13594","article-title":"Explanation for COVID-19 infection neurological damage and reactivations","volume":"67","author":"Roe","year":"2020","journal-title":"Transbound. Emerg. Dis."},{"key":"ref_4","unstructured":"World Health Organization (2021, March 03). WHO Coronavirus Disease (COVID-19) Dashboard. Available online: https:\/\/covid19.who.int\/."},{"key":"ref_5","unstructured":"WHO (2020, October 29). DRAFT Landscape of COVID-19 Candidate Vaccines. Available online: https:\/\/www.who.int\/publications\/m\/item\/draft-landscape-of-covid-19-candidate-vaccines."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1001\/jama.2020.27124","article-title":"Genetic Variants of SARS-CoV-2\u2014What Do They Mean?","volume":"325","author":"Lauring","year":"2021","journal-title":"JAMA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.22207\/JPAM.14.3.01","article-title":"COVID-19 and the World with Co-Morbidities of Heart Disease, Hypertension and Diabetes","volume":"14","author":"Arumugam","year":"2020","journal-title":"J. Pure Appl. Microbiol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Fathi, M., Vakili, K., Sayehmiri, F., Mohamadkhani, A., Hajiesmaeili, M., Rezaei-Tavirani, M., and Eilami, O. (2021). The prognostic value of comorbidity for the severity of COVID-19: A systematic review and meta-analysis study. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0246190"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"264","DOI":"10.2174\/1389200219666180129125436","article-title":"Herbal Immunomodulators\u2014A Remedial Panacea for Designing and Developing Effective Drugs and Medicines: Current Scenario and Future Prospects","volume":"19","author":"Tiwari","year":"2018","journal-title":"Curr. Drug Metab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1007\/s10311-020-01140-4","article-title":"Backward transmission of COVID-19 from humans to animals may propagate reinfections and induce vaccine failure","volume":"19","author":"He","year":"2021","journal-title":"Environ. Chem. Lett."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3043","DOI":"10.1080\/21645515.2020.1807802","article-title":"Coronavirus disease 2019 (COVID-19) in domestic animals and wildlife: Advances and prospects in the development of animal models for vaccine and therapeutic research","volume":"16","author":"Sharun","year":"2020","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"577","DOI":"10.7326\/M20-0504","article-title":"The Incubation Period of Coronavirus Disease 2019 (COVID-19) From Publicly Reported Confirmed Cases: Estimation and Application","volume":"172","author":"Lauer","year":"2020","journal-title":"Ann. Intern. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/ene.14257","article-title":"The need for neurologists in the care of COVID-19 patients","volume":"27","author":"Sellner","year":"2020","journal-title":"Eur. J. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1177\/1747493020923472","article-title":"COVID-19 and stroke\u2014A global World Stroke Organization perspective","volume":"15","author":"Markus","year":"2020","journal-title":"Int. J. Stroke"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1038\/nrendo.2015.6","article-title":"Novel RAAS agonists and antagonists: Clinical applications and controversies","volume":"11","author":"Romero","year":"2015","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Keam, S., Megawati, D., Patel, S.K., Tiwari, R., Dhama, K., and Harapan, H. (2020). Immunopathology and immunotherapeutic strategies in severe acute respiratory syndrome coronavirus 2 infection. Rev. Med. Virol., 30.","DOI":"10.1002\/rmv.2123"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Fara, A., Mitrev, Z., Rosalia, R.A., and Assas, B.M. (2020). Cytokine storm and COVID-19: A chronicle of pro-inflammatory cytokines. Open Biol., 10.","DOI":"10.1098\/rsob.200160"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Wan, S., Yi, Q., Fan, S., Lv, J., Zhang, X., Guo, L., Lang, C., Xiao, Q., Xiao, K., and Yi, Z. (2020). Characteristics of lymphocyte subsets and cytokines in peripheral blood of 123 hospitalized patients with 2019 novel coronavirus pneumonia (NCP). medRxiv.","DOI":"10.1101\/2020.02.10.20021832"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1056\/NEJMra2026131","article-title":"Cytokine Storm","volume":"383","author":"Fajgenbaum","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Zhang, Q., Bastard, P., Liu, Z., Le Pen, J., Moncada-Velez, M., Chen, J., Ogishi, M., Sabli, I.K.D., Hodeib, S., and Korol, C. (2020). Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science, 370.","DOI":"10.1126\/science.abd4570"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Zhang, X., Zhang, Y., Qiao, W., Zhang, J., and Qi, Z. (2020). Baricitinib, a drug with potential effect to prevent SARS-COV-2 from entering target cells and control cytokine storm induced by COVID-19. Int. Immunopharmacol., 86.","DOI":"10.1016\/j.intimp.2020.106749"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2020\/8198963","article-title":"Cytokine Storm in COVID-19 Patients, Its Impact on Organs and Potential Treatment by QTY Code-Designed Detergent-Free Chemokine Receptors","volume":"2020","author":"Mustafa","year":"2020","journal-title":"Mediat. Inflamm."},{"key":"ref_23","first-page":"006","article-title":"Medicinal and therapeutic potential of withanolides from Withania somnifera against COVID-19","volume":"11","author":"Dhawan","year":"2021","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_24","first-page":"36","article-title":"Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: A systematic review and meta-analysis","volume":"10","author":"Yang","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1001\/jama.2020.1585","article-title":"Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus\u2013Infected Pneumonia in Wuhan, China","volume":"323","author":"Wang","year":"2020","journal-title":"JAMA"},{"key":"ref_26","first-page":"1216","article-title":"Cytokine storm of graft-versus-host disease: A critical effector role for inter-leukin-1","volume":"25","author":"Ferrara","year":"1993","journal-title":"Transplant. Proc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1056\/NEJMoa1211721","article-title":"Isolation of a Novel Coronavirus from a Man with Pneumonia in Saudi Arabia","volume":"367","author":"Zaki","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/s10557-020-07120-8","article-title":"Promising Therapy for Heart Failure in Patients with Severe COVID-19: Calming the Cytokine Storm","volume":"35","author":"Peng","year":"2021","journal-title":"Cardiovasc. Drugs Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1002\/path.1440","article-title":"The clinical pathology of severe acute respiratory syndrome (SARS): A report from China","volume":"200","author":"Ding","year":"2003","journal-title":"J. Pathol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.cca.2020.06.017","article-title":"Cytokine storm induced by SARS-CoV-2","volume":"509","author":"Song","year":"2020","journal-title":"Clin. Chim. Acta"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Jamilloux, Y., Henry, T., Belot, A., Viel, S., Fauter, M., El Jammal, T., Walzer, T., Fran\u00e7ois, B., and S\u00e8ve, P. (2020). Should we stimulate or suppress immune responses in COVID-19? Cytokine and anti-cytokine interventions. Autoimmun. Rev., 19.","DOI":"10.1016\/j.autrev.2020.102567"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s40425-018-0343-9","article-title":"Cytokine release syndrome","volume":"6","author":"Subklewe","year":"2018","journal-title":"J. Immunother. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1038\/ni.3153","article-title":"IL-6 as a keystone cytokine in health and disease","volume":"16","author":"Hunter","year":"2015","journal-title":"Nat. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"959","DOI":"10.2217\/imt-2016-0020","article-title":"Immunotherapeutic implications of IL-6 blockade for cytokine storm","volume":"8","author":"Tanaka","year":"2016","journal-title":"Immunotherapy"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0140-6736(03)15326-3","article-title":"Role of interleukin 6 in myocardial dysfunction of meningococcal septic shock","volume":"363","author":"Pathan","year":"2004","journal-title":"Lancet"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"24","DOI":"10.2307\/20034418","article-title":"Preparing for the Next Pandemic","volume":"84","author":"Osterholm","year":"2005","journal-title":"Foreign Aff."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3799","DOI":"10.1073\/pnas.1400593111","article-title":"Mapping the innate signaling cascade essential for cytokine storm during influenza virus infection","volume":"111","author":"Teijaro","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Reghunathan, R., Jayapal, M., Hsu, L.-Y., Chng, H.-H., Tai, D., Leung, B.P., and Melendez, A.J. (2005). Expression profile of immune response genes in patients with Severe Acute Respiratory Syndrome. BMC Immunol., 6.","DOI":"10.1186\/1471-2172-6-2"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1111\/j.1440-1843.2006.00942.x","article-title":"Temporal changes in cytokine\/chemokine profiles and pulmonary involvement in severe acute respiratory syndrome","volume":"11","author":"Chien","year":"2006","journal-title":"Respirology"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Min, C.-K., Cheon, S., Ha, N.-Y., Sohn, K.M., Kim, Y., Aigerim, A., Shin, H.M., Choi, J.-Y., Inn, K.-S., and Kim, J.-H. (2016). Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity. Sci. Rep., 6.","DOI":"10.1038\/srep25359"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/S2213-2600(20)30076-X","article-title":"Pathological findings of COVID-19 associated with acute respiratory distress syndrome","volume":"8","author":"Xu","year":"2020","journal-title":"Lancet Respir. Med."},{"key":"ref_42","first-page":"30132","article-title":"Pulmonary Pathology of Early Phase SARS-COV-2","volume":"1556","author":"Tian","year":"2020","journal-title":"Pneumonia"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.cytogfr.2020.04.002","article-title":"Cytokine storm intervention in the early stages of COVID-19 pneumonia","volume":"53","author":"Sun","year":"2020","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Coperchini, F., Chiovato, L., Ricci, G., Croce, L., Magri, F., and Rotondi, M. (2021). The cytokine storm in COVID-19: Further advances in our understanding the role of specific chemokines involved. Cytokine Growth Factor Rev.","DOI":"10.1016\/j.cytogfr.2020.12.005"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Pum, A., Ennemoser, M., Adage, T., and Kungl, A.J. (2021). Cytokines and Chemokines in SARS-CoV-2 Infections\u2014Therapeutic Strategies Targeting Cytokine Storm. Biomolecules, 11.","DOI":"10.3390\/biom11010091"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1093\/infdis\/jiaa363","article-title":"Serum Cytokine and Chemokine Profile in Relation to the Severity of Coronavirus Disease 2019 in China","volume":"222","author":"Chi","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/j.chom.2020.04.017","article-title":"Heightened Innate Immune Responses in the Respiratory Tract of COVID-19 Patients","volume":"27","author":"Zhou","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1038\/s41587-020-0602-4","article-title":"COVID-19 severity correlates with airway epithelium\u2013immune cell interactions identified by single-cell analysis","volume":"38","author":"Chua","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s10020-020-00230-x","article-title":"IP-10 and MCP-1 as biomarkers associated with disease severity of COVID-19","volume":"26","author":"Chen","year":"2020","journal-title":"Mol. Med."},{"key":"ref_50","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_51","first-page":"463","article-title":"Longitudinal analyses reveal immunological misfiring in severe COVID-19","volume":"584","author":"Lucas","year":"2020","journal-title":"Nat. Cell Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.cell.2020.04.026","article-title":"Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19","volume":"181","author":"Liu","year":"2020","journal-title":"Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.stem.2020.06.015","article-title":"A Human Pluripotent Stem Cell-based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids","volume":"27","author":"Yang","year":"2020","journal-title":"Cell Stem Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.ajpath.2020.08.009","article-title":"Immunopathology of Hyperinflammation in COVID-19","volume":"191","author":"Gustine","year":"2021","journal-title":"Am. J. Pathol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"677","DOI":"10.3389\/fcell.2020.00677","article-title":"Preventing Mortality in COVID-19 Patients: Which Cytokine to Target in a Raging Storm?","volume":"8","author":"Lu","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1126\/science.abb8925","article-title":"Cytokine release syndrome in severe COVID-19","volume":"368","author":"Moore","year":"2020","journal-title":"Science"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2255","DOI":"10.1002\/jcp.30029","article-title":"Neutrophils and Visceral Leishmaniasis: Impact on innate immune response and cross-talks with macrophages and dendritic cells","volume":"236","author":"Kupani","year":"2021","journal-title":"J. Cell. Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Pasrija, R., and Naime, M. (2021). The deregulated immune reaction and cytokines release storm (CRS) in COVID-19 disease. Int. Immunopharmacol., 90.","DOI":"10.1016\/j.intimp.2020.107225"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"37","DOI":"10.3389\/fcimb.2020.00037","article-title":"Pulmonary Macrophage and Dendritic Cell Responses to Cryptococcus neoformans","volume":"10","author":"Nelson","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Smits, S., De Lang, A., Brand, J.V.D., Leijten, L., Van Ijcken, W., Eijkemans, M.J.C., Van Amerongen, G., Kuiken, T., Andeweg, A., and Osterhaus, A. (2010). Exacerbated Innate Host Response to SARS-CoV in Aged Non-Human Primates. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000756"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"7062","DOI":"10.1128\/JVI.00127-09","article-title":"Early Upregulation of Acute Respiratory Distress Syndrome-Associated Cytokines Promotes Lethal Disease in an Aged-Mouse Model of Severe Acute Respiratory Syndrome Coronavirus Infection","volume":"83","author":"Rockx","year":"2009","journal-title":"J. Virol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.chom.2016.01.007","article-title":"Dysregulated Type I Interferon and Inflammatory Monocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice","volume":"19","author":"Channappanavar","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1111\/bjh.14147","article-title":"Advances in the pathogenesis of primary and secondary haemophagocyticlymphohistiocytosis: Differences and similarities","volume":"174","author":"Brisse","year":"2016","journal-title":"Br. J. Haematol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1146\/annurev-med-061813-012806","article-title":"Pathogenesis of Macrophage Activation Syndrome and Potential for Cytokine- Directed Therapies","volume":"66","author":"Schulert","year":"2015","journal-title":"Annu. Rev. Med."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e428","DOI":"10.1016\/S2665-9913(20)30120-X","article-title":"The immunology of COVID-19: Is immune modulation an option for treatment?","volume":"2","author":"Zhong","year":"2020","journal-title":"Lancet Rheumatol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/S1473-3099(13)70154-3","article-title":"Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection","volume":"13","author":"Drosten","year":"2013","journal-title":"Lancet Infect. Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1001\/jama.290.3.374","article-title":"Acute Respiratory Distress Syndrome in Critically Ill Patients With Severe Acute Respiratory Syndrome","volume":"290","author":"Lew","year":"2003","journal-title":"JAMA"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1093\/bib\/bbab045","article-title":"A molecular modelling approach for identifying antiviral selenium-containing heterocyclic compounds that inhibit the main protease of SARS-CoV-2: An in silico investigation","volume":"22","author":"Rakib","year":"2021","journal-title":"Brief. Bioinform."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"9","DOI":"10.7554\/eLife.53725","article-title":"Quantitative analysis of how Myc controls T cell proteomes and metabolic pathways during T cell activation","volume":"9","author":"Marchingo","year":"2020","journal-title":"eLife"},{"key":"ref_70","first-page":"203","article-title":"Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia","volume":"43","author":"Chen","year":"2020","journal-title":"ZhonghuaJie He He Hu Xi Za Zhi"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Chowdhury, K.H., Chowdhury, M.R., Mahmud, S., Tareq, A.M., Hanif, N.B., Banu, N., Reza, A.S.M.A., Emran, T.B., and Simal-Gandara, J. (2020). Drug Repurposing Approach against Novel Coronavirus Disease (COVID-19) through Virtual Screening Targeting SARS-CoV-2 Main Protease. Biology, 10.","DOI":"10.3390\/biology10010002"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1016\/j.jinf.2020.03.037","article-title":"The pathogenesis and treatment of the \u2018Cytokine Storm\u2019 in COVID-19","volume":"80","author":"Ye","year":"2020","journal-title":"J. Infect."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.4049\/jimmunol.1004201","article-title":"Innate Immune Collectin Surfactant Protein D Simultaneously Binds Both Neutrophil Extracellular Traps and Carbohydrate Ligands and Promotes Bacterial Trapping","volume":"187","author":"Douda","year":"2011","journal-title":"J. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/01.CCM.0000149854.61192.DC","article-title":"Lower tidal volume ventilation and plasma cytokine markers of inflammation in patients with acute lung injury","volume":"33","author":"Parsons","year":"2005","journal-title":"Crit. Care Med."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1111\/j.1365-2125.2007.03055.x","article-title":"Clinical uses of interferons","volume":"65","author":"Friedman","year":"2008","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1038\/nrd2422","article-title":"Interferons at age 50: Past, current and future impact on biomedicine","volume":"6","author":"Borden","year":"2007","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1093\/bib\/bbaa428","article-title":"Virtual screening and molecular dynamics simulation study of plant derived compounds to identify potential inhibitor of main protease from SARS-CoV-2","volume":"22","author":"Mahmud","year":"2021","journal-title":"Brief. Bioinform."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/nri2356","article-title":"Colony-stimulating factors in inflammation and autoimmunity","volume":"8","author":"Hamilton","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1479-7364-5-1-30","article-title":"Evolutionary divergence and functions of the human interleukin (IL) gene family","volume":"5","author":"Brocker","year":"2010","journal-title":"Hum. Genom."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Zhang, C., Wu, Z., Li, J.-W., Zhao, H., and Wang, G.-Q. (2020). Cytokine release syndrome in severe COVID-19: Interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. Int. J. Antimicrob. Agents, 55.","DOI":"10.1016\/j.ijantimicag.2020.105954"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"McGonagle, D., Sharif, K., O\u2019Regan, A., and Bridgewood, C. (2020). The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease. Autoimmun. Rev., 19.","DOI":"10.1016\/j.autrev.2020.102537"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1210\/er.2006-0044","article-title":"Role of Chemokines in Endocrine Autoimmune Diseases","volume":"28","author":"Rotondi","year":"2007","journal-title":"Endocr. Rev."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/s41423-018-0005-3","article-title":"Chemokine and chemotactic signals in dendritic cell migration","volume":"15","author":"Tiberio","year":"2018","journal-title":"Cell. Mol. Immunol."},{"key":"ref_84","first-page":"1","article-title":"Chemokines and T Lymphocytes","volume":"9","author":"Ward","year":"1998","journal-title":"Immunology"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"R465","DOI":"10.1530\/ERC-19-0163","article-title":"Role of chemokine receptors in thyroid cancer and immunotherapy","volume":"26","author":"Coperchini","year":"2019","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"S190","DOI":"10.18006\/2020.8(Spl-1-SARS-CoV-2).S190.S201","article-title":"Function and mechanism of angiotensin-converting enzyme-2 receptor to transport sars-cov-2 into the host cells\u2015A review","volume":"8","author":"Bilal","year":"2020","journal-title":"J. Exp. Biol. Agric. Sci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.cell.2020.02.052","article-title":"SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor","volume":"181","author":"Hoffmann","year":"2020","journal-title":"Cell"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.tim.2016.09.001","article-title":"Molecular Evolution of Human Coronavirus Genomes","volume":"25","author":"Forni","year":"2017","journal-title":"Trends Microbiol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.jinf.2020.02.027","article-title":"Identification of the hyper-variable genomic hotspot for the novel coronavirus SARS-CoV-2","volume":"80","author":"Wen","year":"2020","journal-title":"J. Infect."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"E1","DOI":"10.1161\/01.RES.87.5.e1","article-title":"A Novel Angiotensin-Converting Enzyme\u2013Related Carboxypeptidase (ACE2) Converts Angiotensin I to Angiotensin 1-9","volume":"87","author":"Donoghue","year":"2000","journal-title":"Circ. Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.22207\/JPAM.14.3.08","article-title":"Therapeutic Modalities for Sars-Cov-2 (Covid-19): Current Status and Role of Protease Inhibitors to Block Viral Entry Into Host Cells","volume":"14","author":"Qamar","year":"2020","journal-title":"J. Pure Appl. Microbiol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1084\/jem.20050828","article-title":"Multiple organ infection and the pathogenesis of SARS","volume":"202","author":"Gu","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"S66","DOI":"10.18006\/2020.8(Spl-1-SARS-CoV-2).S66.S78","article-title":"Role of toll-like receptors in coronavirus infection and immune response","volume":"8","author":"Iqbal","year":"2020","journal-title":"J. Exp. Biol. Agric. Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"S87","DOI":"10.18006\/2020.8(Spl-1-SARS-CoV-2).S87.S102","article-title":"Severe acute respiratory syndrome coronaviruses and 21st century pandemic: An overview of functional receptors and challenge of therapeutic success","volume":"8","author":"Iqbal","year":"2020","journal-title":"J. Exp. Biol. Agric. Sci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41421-020-0147-1","article-title":"Comparative genetic analysis of the novel coronavirus (2019-nCoV\/SARS-CoV-2) receptor ACE2 in different populations","volume":"6","author":"Cao","year":"2020","journal-title":"Cell Discov."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Mahmudpour, M., Roozbeh, J., Keshavarz, M., Farrokhi, S., and Nabipour, I. (2020). COVID-19 cytokine storm: The anger of inflammation. Cytokine, 133.","DOI":"10.1016\/j.cyto.2020.155151"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/S2468-1253(20)30084-4","article-title":"COVID-19 and the liver: Little cause for concern","volume":"5","author":"Bangash","year":"2020","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.jacc.2008.02.088","article-title":"Detection of Soluble Angiotensin-Converting Enzyme 2 in Heart Failure: Insights Into the Endogenous Counter-Regulatory Pathway of the Renin-Angiotensin-Aldosterone System","volume":"52","author":"Epelman","year":"2008","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_99","first-page":"1280","article-title":"Angiotensin converting enzyme 2 activity and human atrial fibrillation: Increased plasma angiotensin converting enzyme 2 activity is associated with atrial fibrillation and more advanced left atrial structural remodelling","volume":"19","author":"Walters","year":"2016","journal-title":"Europace"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1164\/rccm.202002-0445OC","article-title":"COVID-19 with Different Severities: A Multicenter Study of Clinical Features","volume":"201","author":"Feng","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1002\/biof.6","article-title":"Interferons and viral infections","volume":"35","author":"Fensterl","year":"2009","journal-title":"BioFactors"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1038\/nri2691","article-title":"The IL-1 family: Regulators of immunity","volume":"10","author":"Sims","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Olejnik, J., Hume, A.J., and M\u00fchlberger, E. (2018). Toll-like receptor 4 in acute viral infection: Too much of a good thing. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1007390"},{"key":"ref_104","first-page":"1","article-title":"Corticosteroids in severe COVID-19: A critical view of the evidence","volume":"24","author":"Azoulay","year":"2020","journal-title":"Crit. Care"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/S0165-2427(02)00018-1","article-title":"Chemokines in health and disease","volume":"86","author":"Gangur","year":"2002","journal-title":"Veter-Immunol. Immunopathol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1038\/nrd2805","article-title":"Averting inflammation by targeting the cytokine environment","volume":"9","author":"Kopf","year":"2010","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12941-020-00384-w","article-title":"SARS-CoV-2\/COVID-19 and advances in developing potential therapeutics and vaccines to counter this emerging pandemic","volume":"19","author":"Rabaan","year":"2020","journal-title":"Ann. Clin. Microbiol. Antimicrob."},{"key":"ref_108","first-page":"762","article-title":"Dysregulation of Immune Response in Patients with COVID-19 in Wuhan, China","volume":"71","author":"Qin","year":"2020","journal-title":"SSRN Electron. J."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1002\/jmv.25767","article-title":"Platelet-to-lymphocyte ratio is associated with prognosis in patients with coronavirus disease-19","volume":"92","author":"Qu","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_110","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_111","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_112","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":"Intensiv. Care Med."},{"key":"ref_113","first-page":"2110","article-title":"Sepsis and septic shock in COVID-19: A scoping review of the research data","volume":"146","author":"Lakoh","year":"2021","journal-title":"Research"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Dastoli, S., Bennardo, L., Patruno, C., and Nistic\u00f2, S.P. (2020). Are erythema multiforme and urticaria related to a better outcome of COVID -19?. Dermatol. Ther., 33.","DOI":"10.1111\/dth.13681"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"998","DOI":"10.1093\/nsr\/nwaa041","article-title":"Pathogenic T-cells and inflammatory monocytes incite inflammatory storms in severe COVID-19 patients","volume":"7","author":"Zhou","year":"2020","journal-title":"Natl. Sci. Rev."},{"key":"ref_116","first-page":"E009","article-title":"A pathological report of three COVID-19 cases by minimally invasive autopsies","volume":"49","author":"Yao","year":"2020","journal-title":"ZhonghuaJie He He Hu Xi Za Zhi"},{"key":"ref_117","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_118","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990\u20132017: Analysis for the Global Burden of Disease Study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1097\/CCM.0000000000003260","article-title":"Presenting Symptoms Independently Predict Mortality in Septic Shock","volume":"46","author":"Filbin","year":"2018","journal-title":"Crit. Care Med."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1164\/rccm.201811-2148ED","article-title":"The Search for Efficacious New Therapies in Sepsis Needs to Embrace Heterogeneity","volume":"199","author":"Scicluna","year":"2019","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/s41591-020-0752-4","article-title":"An immune-cell signature of bacterial sepsis","volume":"26","author":"Reyes","year":"2020","journal-title":"Nat. Med."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"8","DOI":"10.7554\/eLife.43803","article-title":"Identifying gene expression programs of cell-type identity and cellular activity with single-cell RNA-Seq","volume":"8","author":"Kotliar","year":"2019","journal-title":"eLife"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-018-03078-2","article-title":"A community approach to mortality prediction in sepsis via gene expression analysis","volume":"9","author":"Sweeney","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1126\/science.abc6261","article-title":"Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans","volume":"369","author":"Arunachalam","year":"2020","journal-title":"Science"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Rakib, A., Sami, S.A., Islam, M.A., Ahmed, S., Faiz, F.B., Khanam, B.H., Marma, K.K.S., Rahman, M., Uddin, M.M.N., and Nainu, F. (2020). Epitope-based immunoinformatics approach on nucleocapsid protein of severe acute respiratory syndrome-coronavirus-2. Molecules, 25.","DOI":"10.21203\/rs.3.rs-37055\/v1"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1038\/s41591-020-0944-y","article-title":"A single-cell atlas of the peripheral immune response in patients with severe COVID-19","volume":"26","author":"Wilk","year":"2020","journal-title":"Nat. Med."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Lee, J.S., Park, S., Jeong, H.W., Ahn, J.Y., Choi, S.J., Lee, H., Choi, B., Nam, S.K., Sa, M., and Kwon, J.-S. (2020). Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19. Sci. Immunol., 5.","DOI":"10.1126\/sciimmunol.abd1554"},{"key":"ref_128","doi-asserted-by":"crossref","unstructured":"Chugh, H., Awasthi, A., Agarwal, Y., Gaur, R.K., Dhawan, G., and Chandra, R. (2021). A comprehensive review on potential therapeutics interventions for COVID-19. Eur. J. Pharmacol., 890.","DOI":"10.1016\/j.ejphar.2020.173741"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1","DOI":"10.7324\/JAPS.2020.10501","article-title":"Repurposing antivirals as potential treatments for SARS-CoV-2: From SARS to COVID-19","volume":"10","year":"2020","journal-title":"J. Appl. Pharm. Sci."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s40265-020-01367-z","article-title":"Pharmaco-Immunomodulatory Therapy in COVID-19","volume":"80","author":"Rizk","year":"2020","journal-title":"Drugs"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.ijsu.2020.08.038","article-title":"Dexamethasone to combat cytokine storm in COVID-19: Clinical trials and preliminary evidence","volume":"82","author":"Sharun","year":"2020","journal-title":"Int. J. Surg."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1080\/14712598.2020.1796963","article-title":"Antibody-based immunotherapeutics and use of convalescent plasma to counter COVID-19: Advances and prospects","volume":"20","author":"Sharun","year":"2020","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"m1432","DOI":"10.1136\/bmj.m1432","article-title":"Chloroquine and hydroxychloroquine in covid-19","volume":"369","author":"Ferner","year":"2020","journal-title":"BMJ"},{"key":"ref_134","unstructured":"Yatoo, M.I., Hamid, Z., Rather, I., Nazir, Q.U.A., Bhat, R.A., Haq, A.U., Magray, S.N., Haq, Z., Sah, R., and Tiwari, R. (2021). Immunotherapies and immunomodulatory approaches in clinical trials\u2014A mini review. Hum. Vaccines Immunother., 1\u201313."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1007\/s10067-020-05073-9","article-title":"Rheumatologists\u2019 perspective on coronavirus disease 19 (COVID-19) and potential therapeutic targets","volume":"39","author":"Misra","year":"2020","journal-title":"Clin. Rheumatol."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Rayman, G., Lumb, A.N., Kennon, B., Cottrell, C., Nagi, D., Page, E., Voigt, D., Courtney, H.C., Atkins, H., and Higgins, K. (2021). Dexamethasone therapy in COVID-19 patients: Implications and guidance for the management of blood glucose in people with and without diabetes. Diabet. Med., 38.","DOI":"10.1111\/dme.14378"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/s41392-021-00496-5","article-title":"Clinical evidence of an interferon\u2013glucocorticoid therapeutic synergy in COVID-19","volume":"6","author":"Lu","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/s41392-020-00310-8","article-title":"Convalescent plasma therapy for COVID-19: A tried-and-true old strategy?","volume":"5","author":"Xi","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"2963","DOI":"10.1080\/21645515.2020.1808410","article-title":"COVID-19: Benefits and risks of passive immunotherapeutics","volume":"16","author":"Gupta","year":"2020","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1080\/01652176.2020.1867776","article-title":"SARS-CoV-2 infection in farmed minks, associated zoonotic concerns, and importance of the One Health approach during the ongoing COVID-19 pandemic","volume":"41","author":"Sharun","year":"2021","journal-title":"Veter. Q."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.jcyt.2020.08.009","article-title":"Antibodies at work in the time of severe acute respiratory syndrome coronavirus 2","volume":"23","author":"Sajna","year":"2021","journal-title":"Cytotherapy"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"678","DOI":"10.5414\/CP203890","article-title":"COVID-19: Cytokine storm modulation\/blockade with oral polyvalent immunoglobulins (PVIG, KMP01D): A potential and safe therapeutic agent (Primum nil nocere)","volume":"58","author":"Sly","year":"2020","journal-title":"Int. J. Clin. Pharmacol. Ther."},{"key":"ref_143","first-page":"121","article-title":"Severe acute respiratory syndrome: Clinical and laboratory manifestations","volume":"25","author":"Lam","year":"2004","journal-title":"Clin. Biochem. Rev."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Metcalfe, S.M. (2020). Mesenchymal stem cells and management of COVID-19 pneumonia. Med. Drug Discov., 5.","DOI":"10.1016\/j.medidd.2020.100019"},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Sadeghi, S., Soudi, S., Shafiee, A., and Hashemi, S.M. (2020). Mesenchymal stem cell therapies for COVID-19: Current status and mechanism of action. Life Sci., 262.","DOI":"10.1016\/j.lfs.2020.118493"},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Xiong, J., Chen, L., Zhang, L., Bao, L., and Shi, Y. (2021). Mesenchymal Stromal Cell-Based Therapy: A Promising Approach for Severe COVID-19. Cell Transplant., 30.","DOI":"10.1177\/0963689721995455"},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Jeyaraman, M., John, A., Koshy, S., Ranjan, R., Anudeep, T.C., Jain, R., Swati, K., Jha, N.K., Sharma, A., and Kesari, K.K. (2021). Fostering mesenchymal stem cell therapy to halt cytokine storm in COVID-19. Biochim. Biophys. Acta Mol. Basis Dis., 1867.","DOI":"10.1016\/j.bbadis.2020.166014"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1080\/21645515.2017.1316909","article-title":"Tocilizumab (Actemra)","volume":"13","author":"Sheppard","year":"2017","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"10970","DOI":"10.1073\/pnas.2005615117","article-title":"Effective treatment of severe COVID-19 patients with tocilizumab","volume":"117","author":"Xu","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"e30","DOI":"10.1016\/S0140-6736(20)30304-4","article-title":"Baricitinib as potential treatment for 2019-nCoV acute respiratory disease","volume":"395","author":"Richardson","year":"2020","journal-title":"Lancet"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1136\/annrheumdis-2019-216653","article-title":"Safety of synthetic and biological DMARDs: A systematic literature review informing the 2019 update of the EULAR recommendations for the management of rheumatoid arthritis","volume":"79","author":"Sepriano","year":"2020","journal-title":"Ann. Rheum. Dis."},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Yeleswaram, S., Smith, P., Burn, T., Covington, M., Juvekar, A., Li, Y., Squier, P., and Langmuir, P. (2020). Inhibition of cytokine signaling by ruxolitinib and implications for COVID-19 treatment. Clin. Immunol., 218.","DOI":"10.1016\/j.clim.2020.108517"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/S1473-3099(20)30270-X","article-title":"Baricitinib for COVID-19: A suitable treatment?\u2014Authors\u2019 reply","volume":"20","author":"Richardson","year":"2020","journal-title":"Lancet Infect. Dis."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1016\/S0140-6736(20)30858-8","article-title":"Trials of anti-tumour necrosis factor therapy for COVID-19 are urgently needed","volume":"395","author":"Feldmann","year":"2020","journal-title":"Lancet"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"466","DOI":"10.3389\/fmed.2020.00466","article-title":"Ruxolitinib Rapidly Reduces Acute Respiratory Distress Syndrome in COVID-19 Disease. Analysis of Data Collection From RESPIRE Protocol","volume":"7","author":"Capochiani","year":"2020","journal-title":"Front. Med."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"65","DOI":"10.15171\/ijoem.2020.1921","article-title":"The Novel Coronavirus: A Bird\u2019s Eye View","volume":"11","author":"Habibzadeh","year":"2020","journal-title":"Int. J. Occup. Environ. Med."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.jsps.2020.12.018","article-title":"Immune system response during viral Infections: Immunomodulators, cytokine storm (CS) and Immunotherapeutics in COVID-19","volume":"29","author":"Pottoo","year":"2021","journal-title":"Saudi Pharm. J."},{"key":"ref_158","doi-asserted-by":"crossref","unstructured":"Iannone, L.F., Bennardo, L., Palleria, C., Roberti, R., De Sarro, C., Naturale, M.D., Dastoli, S., Donato, L., Manti, A., and Valenti, G. (2020). Safety profile of biologic drugs for psoriasis in clinical practice: An Italian prospective pharmacovigilance study. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0241575"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"2566","DOI":"10.1002\/1521-4141(200109)31:9<2566::AID-IMMU2566>3.0.CO;2-L","article-title":"Inhibition of tumor necrosis factor reduces the severity of virus-specific lung immunopathology","volume":"31","author":"Hussell","year":"2001","journal-title":"Eur. J. Immunol."},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Gasparello, J., Finotti, A., and Gambari, R. (2021). Tackling the COVID-19 \u201ccytokine storm\u201d with microRNA mimics directly targeting the 3\u2032UTR of pro-inflammatory mRNAs. Med. Hypotheses, 146.","DOI":"10.1016\/j.mehy.2020.110415"},{"key":"ref_161","first-page":"1","article-title":"Potential role for interferon gamma in the treatment of recurrent ventilator-acquired pneumonia in patients with COVID-19: A hypothesis","volume":"2021","author":"Nguyen","year":"2021","journal-title":"Intensiv. Care Med."},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Ebrahimi, N., Aslani, S., Babaie, F., Hemmatzadeh, M., Hosseinzadeh, R., Joneidi, Z., Tourzani, Z.M., Pakravan, N., and Mohammadi, H. (2020). Recent findings on the Coronavirus disease 2019 (COVID-19); immunopathogenesis and immunotherapeutics. Int. Immunopharmacol., 89.","DOI":"10.1016\/j.intimp.2020.107082"},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Khosroshahi, L.M., Rokni, M., Mokhtari, T., and Noorbakhsh, F. (2021). Immunology, immunopathogenesis and immunotherapeutics of COVID-19; an overview. Int. Immunopharmacol., 93.","DOI":"10.1016\/j.intimp.2020.107364"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"236","DOI":"10.2174\/1389200219666180129145252","article-title":"Medicinal and therapeutic potential of herbs and plant metabolites\/extracts countering viral pathogens-current knowledge and future prospects","volume":"19","author":"Dhama","year":"2018","journal-title":"Curr. Drug Metab."},{"key":"ref_165","doi-asserted-by":"crossref","unstructured":"Rakib, A., Paul, A., Ahmed, S., Chy, M.N.U., Sami, S.A., Baral, S.K., Majumder, M., Tareq, A.T., Amin, M.N., and Shahriar, A. (2020). Biochemical and computational approach of phytocompounds from Tinospora crispa in the management of COVID-19. Molecules, 25.","DOI":"10.3390\/molecules25173936"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.cnur.2020.10.007","article-title":"Herbal Medication to Enhance or Modulate Viral Infections","volume":"56","author":"Tahmasbi","year":"2021","journal-title":"Nurs. Clin. N. Am."},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Runfeng, L., Yunlong, H., Jicheng, H., Weiqi, P., Qinhai, M., Yongxia, S., Chufang, L., Jin, Z., Zhenhua, J., and Haiming, J. (2020). Lianhuaqingwen exerts anti-viral and anti-inflammatory activity against novel coronavirus (SARS-CoV-2). Pharmacol. Res., 156.","DOI":"10.1016\/j.phrs.2020.104761"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13020-020-00419-6","article-title":"Traditional Chinese herbal medicine-potential therapeutic application for the treatment of COVID-19","volume":"16","author":"Capodice","year":"2021","journal-title":"Chin. Med."},{"key":"ref_169","first-page":"1","article-title":"Early therapeutic interventions of traditional Chinese medicine in COVID-19 patients: A retrospective cohort study","volume":"2021","author":"Shi","year":"2021","journal-title":"J. Integr. Med."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"7809","DOI":"10.1073\/pnas.0711241105","article-title":"Modulation of TNF- -converting enzyme by the spike protein of SARS-CoV and ACE2 induces TNF-\u03b1 production and facilitates viral entry","volume":"105","author":"Haga","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"1703531","DOI":"10.1080\/19420862.2019.1703531","article-title":"Antibodies to watch in 2020","volume":"12","author":"Kaplon","year":"2020","journal-title":"mAbs"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"4801","DOI":"10.1158\/0008-5472.CAN-19-1167","article-title":"Recent Advances Targeting CCR5 for Cancer and Its Role in Immuno-Oncology","volume":"79","author":"Jiao","year":"2019","journal-title":"Cancer Res."},{"key":"ref_173","doi-asserted-by":"crossref","unstructured":"Prokunina-Olsson, L., Alphonse, N., Dickenson, R.E., Durbin, J.E., Glenn, J.S., Hartmann, R., Kotenko, S.V., LaZear, H.M., O\u2019Brien, T.R., and Odendall, C. (2020). COVID-19 and emerging viral infections: The case for interferon lambda. J. Exp. Med., 217.","DOI":"10.1084\/jem.20200653"},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13287-020-01678-8","article-title":"Mesenchymal stem cells as a potential therapy for COVID-19","volume":"11","author":"Liu","year":"2020","journal-title":"Stem Cell Res. Ther."},{"key":"ref_175","first-page":"1","article-title":"Mesenchymal Stem Cell Therapy for Severe COVID-19 ARDS","volume":"2021","author":"Magunia","year":"2021","journal-title":"J. Intensiv. Care Med."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"139","DOI":"10.4252\/wjsc.v13.i2.139","article-title":"Targeting mesenchymal stem cell therapy for severe pneumonia patients","volume":"13","author":"Lam","year":"2021","journal-title":"World J. Stem Cells"},{"key":"ref_177","doi-asserted-by":"crossref","unstructured":"Rakib, A., Sami, S.A., Mimi, N.J., Chowdhury, M.M., Eva, T.A., Nainu, F., Paul, A., Shahriar, A., Tareq, A.M., and Emon, N.U. (2020). Immunoinformatics-guided design of an epitope-based vaccine against severe acute respiratory syndrome coronavirus 2 spike glycoprotein. Comput. Biol. Med., 124.","DOI":"10.1016\/j.compbiomed.2020.103967"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"ofaa102","DOI":"10.1093\/ofid\/ofaa102","article-title":"High-Dose Intravenous Immunoglobulin as a Therapeutic Option for Deteriorating Patients With Coronavirus Disease 2019","volume":"7","author":"Cao","year":"2020","journal-title":"Open Forum Infect. Dis."},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"2675","DOI":"10.1002\/jmv.26727","article-title":"Administration of intravenous immunoglobulin in the treatment of COVID-19: A review of available evidence","volume":"93","author":"Moradimajd","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"102554","DOI":"10.1016\/j.autrev.2020.102554","article-title":"Convalescent plasma in Covid-19: Possible mechanisms of action","volume":"19","author":"Rojas","year":"2020","journal-title":"Autoimmun. Rev."},{"key":"ref_181","doi-asserted-by":"crossref","unstructured":"Mattos-Silva, P., Felix, N.S., Silva, P.L., Robba, C., Battaglini, D., Pelosi, P., Rocco, P.R.M., and Cruz, F.F. (2020). Pros and cons of corticosteroid therapy for COVID-19 patients. Respir. Physiol. Neurobiol., 280.","DOI":"10.1016\/j.resp.2020.103492"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1097\/00004836-200110000-00006","article-title":"Side Effects of Corticosteroid Therapy","volume":"33","author":"Buchman","year":"2001","journal-title":"J. Clin. Gastroenterol."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"2954","DOI":"10.1080\/21645515.2020.1818522","article-title":"BCG vaccine: A hope to control COVID-19 pandemic amid crisis","volume":"16","author":"Malik","year":"2020","journal-title":"Hum. 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