{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T05:37:39Z","timestamp":1762061859962,"version":"build-2065373602"},"reference-count":32,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T00:00:00Z","timestamp":1660089600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Princess Nourah bint Abdulrahman University Researchers Supporting Project","award":["PNURSP2022R30"],"award-info":[{"award-number":["PNURSP2022R30"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Background and objectives: COVID-19 patients exhibit a broad range of manifestations, presenting with a flu-like respiratory tract infection that can advance to a systemic and severe disease characterized by pneumonia, pulmonary edema, severe damage to the airways, and acute respiratory distress syndrome (ARDS, causing fatality in 70% of COVID-19 cases). A \u2018cytokine storm\u2019 profile is found in most severely influenced COVID-19 patients. The treatment protocol of the disease also includes tocilizumab, which is a humanized monoclonal antibody used to treat autoimmune and inflammatory conditions. This study was designed (1) to assess the role of tocilizumab in COVID-19 patients regarding therapeutic efficacy through evaluation of cytokine release syndrome (CRS) resolution and anticoagulant effect, analyzing clinical safety via monitoring of associated adverse effects profile; and (2) to compare the clinical safety and therapeutic efficacy of institutional treatment regimen (alone) versus tocilizumab added to an institutional treatment module in COVID-19 patients. Materials and Methods: In this study, the endpoints parametric assessment of severely diseased patients of COVID-19 was performed (total n = 172, control group (institutional protocol treatment provided), n = 101 and test group (tocilizumab provided), n = 71) at the Khyber Teaching Institution, MTI, Peshawar. The assessments were compared using non-parametric analyses at baseline and after a follow-up of 12\u201318 days until the patient discharged or expired. Results: Results of the study revealed an insignificant difference among the control vs. test group in resolving inflammatory parameters (C-reactive protein (CRP) 21.30 vs. 50.07; p = 0.470, ferritin 482.9 vs. 211.5; p = 0.612, lactate dehydrogenase (LDH) 29.12 vs.18.8; p = 0.0863, and D-dimer 464 vs.164.4; p = 0.131). However, a statistically significant difference was found between the control group and test group regarding coagulation parameters (international normalized ratio (INR) 0.12 vs. \u22120.07; p \u2264 0.001; activated partial thromboplastin time (aPTT) 0.42 vs. \u22121.16; p \u2264 0.001; prothrombin time (PT) 0.31 vs. \u22120.96; p \u2264 0.001; platelet count \u221212.34 vs. \u22121.47; p = 0.012) and clinical survival rate (89.10 vs. 90.14; p &lt; 0.001). Furthermore, there was significantly higher infection rates and raised alanine aminotransferase (ALT) and alkaline phosphatase (ALP) associated with the tocilizumab group as compared to those receiving institutional treatment (bacterial infections: 0.99% vs. 15.49%; p \u2264 0.01, ALT: 3.96% vs. 28.16%; p \u2264 0.01, ALP: 1.98% vs. 22.53%; p \u2264 0.01). Conclusions: From this study, it was concluded that tocilizumab can be a better drug of choice in terms of efficacy, particularly in resolving coagulopathy in severe COVID-19 patients.<\/jats:p>","DOI":"10.3390\/medicina58081076","type":"journal-article","created":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T09:42:56Z","timestamp":1660124576000},"page":"1076","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Assessment of Tocilizumab (Humanized Monoclonal Antibody) for Therapeutic Efficacy and Clinical Safety in Patients with Coronavirus Disease (COVID-19)"],"prefix":"10.3390","volume":"58","author":[{"given":"Sami","family":"Ullah","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University of Peshawar, Peshawar 25120, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Radhya","family":"Abid","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Peshawar, Peshawar 25120, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sana","family":"Haider","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, CECOS University of Science and Technology, Peshawar 25120, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6847-1744","authenticated-orcid":false,"given":"Fazli","family":"Khuda","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Peshawar, Peshawar 25120, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5657-4650","authenticated-orcid":false,"given":"Ghadeer M.","family":"Albadrani","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Riyadh 11671, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jawaher A.","family":"Abdulhakim","sequence":"additional","affiliation":[{"name":"Medical Laboratory Department, College of Applied Medical Sciences, Taibah University, Yanbu 46522, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6210-3628","authenticated-orcid":false,"given":"Ahmed E.","family":"Altyar","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4341-2713","authenticated-orcid":false,"given":"Mohamed M.","family":"Abdel-Daim","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, Jeddah 21442, Saudi Arabia"},{"name":"Department of Pharmacology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia 41522, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Syed Muhammad Ashhad","family":"Halimi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Peshawar, Peshawar 25120, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1450-5635","authenticated-orcid":false,"given":"Atif Ali Khan","family":"Khalil","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy, Faculty of Pharmaceutical and Allied Health Sciences, Lahore College for Women University, Jail Road, Lahore 54000, Pakistan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,10]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2021, May 07). Novel Coronavirus-China. Available online: http:\/\/www.who.int\/csr\/don\/12-january-2020-novel-coronavirus-china\/en\/."},{"key":"ref_2","first-page":"157","article-title":"WHO Declares COVID-19 a Pandemic","volume":"91","author":"Cucinotta","year":"2020","journal-title":"Acta Bio-Med. Atenei Parm."},{"key":"ref_3","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-Infected Pneumonia in Wuhan, China","volume":"323","author":"Wang","year":"2020","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1056\/NEJMoa2004500","article-title":"COVID-19 in Critically Ill Patients in the Seattle Region\u2014Case Series","volume":"382","author":"Bhatraju","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_5","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_6","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_7","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_8","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.ccc.2019.12.004","article-title":"Coagulation Disorders in Hemophagocytic Lymphohistiocytosis\/Macrophage Activation Syndrome","volume":"36","author":"Valade","year":"2020","journal-title":"Crit. Care Clin."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1634\/theoncologist.2018-0028","article-title":"FDA Approval Summary: Tocilizumab for Treatment of Chimeric Antigen Receptor T Cell-Induced Severe or Life-Threatening Cytokine Release Syndrome","volume":"23","author":"Le","year":"2018","journal-title":"Oncologist"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/S2352-3026(20)30145-9","article-title":"Coagulation abnormalities and thrombosis in patients with COVID-19","volume":"7","author":"Levi","year":"2020","journal-title":"Lancet Haematol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/S0140-6736(20)30566-3","article-title":"Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study","volume":"395","author":"Zhou","year":"2020","journal-title":"Lancet"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"12421","DOI":"10.15252\/emmm.202012421","article-title":"The role of interleukin-6 in monitoring severe case of coronavirus disease 2019","volume":"12","author":"Liu","year":"2020","journal-title":"EMBO Mol. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.ejim.2020.10.020","article-title":"Interleukin-6 receptor blockade with subcutaneous tocilizumab improves coagulation activity in patients with COVID-19","volume":"83","author":"Potere","year":"2021","journal-title":"Eur. J. Intern. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.ejim.2020.05.021","article-title":"Efficacy and safety of tocilizumab in severe COVID-19 patients: A single-centre retrospective cohort study","volume":"76","author":"Campochiaro","year":"2020","journal-title":"Eur. J. Intern. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"121","DOI":"10.4103\/0253-7176.116232","article-title":"How to calculate sample size for different study designs in medical research?","volume":"35","author":"Charan","year":"2013","journal-title":"Indian J. Psychol. Med."},{"key":"ref_16","unstructured":"World Health Organization (2021, May 25). R&D Blueprint Novel Coronavirus. (n.d). Available online: https:\/\/www.who.int\/teams\/blueprint\/covid-19."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1056\/NEJMoa2001282","article-title":"A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe COVID-19","volume":"382","author":"Cao","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1007\/s43441-020-00159-7","article-title":"Data Monitoring for the Chinese Clinical Trials of Remdesivir in Treating Patients with COVID-19 during the Pandemic Crisis","volume":"54","author":"Shih","year":"2020","journal-title":"Ther. Innov. Regul. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1093\/rheumatology\/keu035","article-title":"Effects of IL-6 and IL-6 blockade on neutrophil function in vitro and in vivo","volume":"53","author":"Wright","year":"2014","journal-title":"Rheumatology"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kuhn, K.A., Manieri, N.A., Liu, T.C., and Stappenbeck, T.S. (2014). IL-6 stimulates intestinal epithelial proliferation and repair after injury. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0114195"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1097\/CCM.0000000000004895","article-title":"The Surviving Sepsis Campaign: Research Priorities for Coronavirus Disease 2019 in Critical Illness","volume":"49","author":"Coopersmith","year":"2021","journal-title":"Crit. Care Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"102452","DOI":"10.1016\/j.jaut.2020.102452","article-title":"Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)?","volume":"111","author":"Liu","year":"2020","journal-title":"J. Autoimmun."},{"key":"ref_23","first-page":"30284","article-title":"Tocilizumab for severe COVID-19 pneumonia","volume":"9913","author":"Piano","year":"2020","journal-title":"Lancet Rheumatol."},{"key":"ref_24","first-page":"e15208","article-title":"Tocilizumab and Thromboembolism in COVID-19: A Retrospective Hospital-Based Cohort Analysis","volume":"13","author":"Chan","year":"2021","journal-title":"Cureus"},{"key":"ref_25","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_26","doi-asserted-by":"crossref","first-page":"E474","DOI":"10.1016\/S2665-9913(20)30173-9","article-title":"Tocilizumab in patients with severe COVID-19: A retrospective cohort study","volume":"2","author":"Giovanni","year":"2020","journal-title":"Lancet-Rheumatol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"759","DOI":"10.15585\/mmwr.mm6924e2","article-title":"Coronavirus Disease 2019 Case Surveillance","volume":"69","author":"Stokes","year":"2020","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1007\/s11481-020-09974-z","article-title":"Is COVID-19 Gender-sensitive?","volume":"16","author":"Mukherjee","year":"2021","journal-title":"Off. J. Soc. NeuroImmune Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"77","DOI":"10.22146\/jcoemph.57325","article-title":"Current prevalence, characteristics, and comorbidities of patients with COVID-19 in Indonesia","volume":"3","author":"Karyono","year":"2020","journal-title":"J. Community Empower. Health"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2000547","DOI":"10.1183\/13993003.00547-2020","article-title":"Comorbidity and its impact on 1590 patients with COVID-19 in China: A nationwide analysis","volume":"55","author":"Guan","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1016\/j.gaceta.2021.10.085","article-title":"Comorbidities and mortality in COVID-19 patients","volume":"35","author":"Djaharuddin","year":"2021","journal-title":"Gac. Sanit."},{"key":"ref_32","unstructured":"Mullen, B. (2022, March 03). American College of Cardiology. Available online: https:\/\/www.acc.org\/\/~\/media\/Non-Clinical\/Files-PDFs-Excel-MS-Word-etc\/2020\/02\/S20028-ACC-Clinical-Bulletin-Coronavirus.pdf."}],"container-title":["Medicina"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1648-9144\/58\/8\/1076\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:06:46Z","timestamp":1760141206000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1648-9144\/58\/8\/1076"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,10]]},"references-count":32,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["medicina58081076"],"URL":"https:\/\/doi.org\/10.3390\/medicina58081076","relation":{},"ISSN":["1648-9144"],"issn-type":[{"type":"electronic","value":"1648-9144"}],"subject":[],"published":{"date-parts":[[2022,8,10]]}}}