{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T13:17:57Z","timestamp":1770556677879,"version":"3.49.0"},"reference-count":27,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T00:00:00Z","timestamp":1633478400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background: As COVID-19 has neither a standard treatment protocol nor guidelines, there are many treatment protocols for anti-inflammatory corticosteroids and anti-coagulations for severe COVID-19 pneumonia patients. This study aimed to assess the most suitable modality in this high-risk group. Methods: A prospective, experimental study design was adopted that included 123 severe COVID-19 pneumonia patients admitted at Assiut University Hospital. Patients were divided into three groups according to a combined corticosteroid and anticoagulants therapy protocol. Group A included 32 patients, group B included 45 patients, and group C included 46 patients. Assessment of cases was conducted according to the treatment type and duration, weaning duration from oxygen therapy, length of hospital and ICU stay, and complications during treatment. Three months follow-up after discharge was performed. Results: the three patient groups showed significant differences regarding the 3-month outcome, whereas Group C showed the highest cure rate, lowest lung fibrosis, and lowest mortality rate over the other two groups. The in-hospital outcome, the development of pulmonary embolism, bleeding, hematoma, acute kidney disease, and myocardial infarction showed a significant difference between groups (p values &lt; 0.05). Mortality predictors among severe COVID-19 patients by multivariable Cox hazard regression included treatment modality, history of comorbid diseases, increased C reactive protein, high neutrophil-lymphocyte ratio, and shorter ICU and hospital stay. Conclusion: the use of combined methylprednisolone and therapeutic Enoxaparin, according to a flexible protocol for COVID-19 patients with severe pneumonia, had two benefits; the prevention of disease complications and improved clinical outcome.<\/jats:p>","DOI":"10.3390\/antibiotics10101214","type":"journal-article","created":{"date-parts":[[2021,10,6]],"date-time":"2021-10-06T10:36:57Z","timestamp":1633516617000},"page":"1214","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Challenges in Steroid and Anticoagulant Therapy in Severe COVID-19 Pneumonia: A Prospective Study"],"prefix":"10.3390","volume":"10","author":[{"given":"Alaa Thabet","family":"Hassan","sequence":"first","affiliation":[{"name":"Chest Department, Faculty of Medicine, Assiut University, 71515 Assiut, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3708-0553","authenticated-orcid":false,"given":"Alaa E. Abd","family":"Elmoniem","sequence":"additional","affiliation":[{"name":"Internal and Critical Care Medicine Department, Faculty of Medicine, Assiut University, 71515 Assiut, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1637-4341","authenticated-orcid":false,"given":"Marwa Mahmoud","family":"Abdelrady","sequence":"additional","affiliation":[{"name":"Anesthesia and ICU Department, Faculty of Medicine, Assiut University, 71515 Assiut, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mona Embarek","family":"Mohamed","sequence":"additional","affiliation":[{"name":"Medical Microbiology and Immunology Department, Faculty of Medicine, Assiut University, 71515 Assiut, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1943-8419","authenticated-orcid":false,"given":"Mohamed A.","family":"Mokhtar","sequence":"additional","affiliation":[{"name":"Medical Microbiology and Immunology Department, Faculty of Medicine, Assiut University, 71515 Assiut, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdelhalim A.","family":"Elsherif","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology Department, Faculty of Medicine, Al-Azhar University, 71515 Assiut, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ghada Mohamed","family":"Saied","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology Department, Faculty of Medicine, Assiut University, 71515 Assiut, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0226-0271","authenticated-orcid":false,"given":"Soheir M.","family":"Kasem","sequence":"additional","affiliation":[{"name":"Internal and Critical Care Medicine Department, Faculty of Medicine, Assiut University, 71515 Assiut, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1007\/s00134-020-06022-5","article-title":"Surviving Sepsis Campaign: Guidelines on the Management of Critically Ill Adults with Coronavirus Disease 2019 (COVID-19)","volume":"46","author":"Alhazzani","year":"2020","journal-title":"Intensive Care Med."},{"key":"ref_2","unstructured":"Rezaie, S. (2020, December 10). COVID-19: Clinical\/Therapeutic Staging Proposal and Treatment: REBEL EM Blog. Available online: https:\/\/rebelem.com\/covid-19-clinical-therapeutic-staging-proposal-and-treatment."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e00310-20","DOI":"10.1128\/JCM.00310-20","article-title":"Improved Molecular Diagnosis of COVID-19 by the Novel, Highly Sensitive and Specific COVID-19-RdRp\/Hel Real-Time Reverse Transcription-PCR Assay Validated In Vitro and with Clinical Specimens","volume":"58","author":"Chan","year":"2020","journal-title":"J. Clin. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e13549","DOI":"10.1111\/dth.13549","article-title":"Cutaneous Signs in COVID-19Patients: A Review","volume":"33","author":"Wollina","year":"2020","journal-title":"Dermatol. Ther."},{"key":"ref_5","first-page":"1824","article-title":"Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review","volume":"323","author":"Sanders","year":"2020","journal-title":"JAMA"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Bhimraj, A., Morgan, R.L., Shumaker, A.H., Lavergne, V., Baden, L., Cheng, V.C.C., Edwards, K.M., Gandhi, R., Muller, W.J., and O\u2019Horo, J.C. Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19. Clin. Infect. Dis., 2020.","DOI":"10.1093\/cid\/ciaa478"},{"key":"ref_7","unstructured":"World Health Organization (2020). Testing for 2019 Novel Coronavirus (2019-nCoV) in Suspected Human Cases: Interim Guidance, 14 January 2020. Bull. World Health Organ., Available online: https:\/\/www.who.int\/publications\/i\/item\/10665-331501."},{"key":"ref_8","unstructured":"Epidemiology Working Group for NCIP Epidemic Response CCfDCaP (2020). The Epidemiological Characteristics of an Outbreak of 2019 Novel Coronavirus Diseases (COVID-19) in China. Zhonghualiuxingbingxuezazhi, 41, 145\u2013151."},{"key":"ref_9","first-page":"14","article-title":"Blood Gas and pH Analysis and Related Measurements","volume":"21","author":"Wayne","year":"2009","journal-title":"Approv. Guidel."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/cid\/ciaa601","article-title":"Early Short-Course Corticosteroids in Hospitalized Patients With COVID-19","volume":"71","author":"Fadel","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1080\/22221751.2020.1746199","article-title":"Hypothesis for Potential Pathogenesis of SARS-CoV-2 Infection\u2014A Review of Immune Changes in Patients with Viral Pneumonia","volume":"9","author":"Lin","year":"2020","journal-title":"Emerg. Microbes Infect."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.ijid.2021.03.021","article-title":"Peculiar Clinical Presentation of COVID-19 and Predictors of Mortality in the Elderly: A MulticentreRetrospective Cohort study","volume":"105","author":"Bavaro","year":"2021","journal-title":"Int. J. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/s41422-020-0327-4","article-title":"COVID-19: Towards Understanding of Pathogenesis","volume":"30","author":"Cao","year":"2020","journal-title":"Cell Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"104761","DOI":"10.1016\/j.phrs.2020.104761","article-title":"Lianhuaqingwen Exerts Anti-Viral and Anti-Inflammatory Activity Against Novel Coronavirus (SARS-CoV-2)","volume":"156","author":"Runfeng","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.healun.2020.03.012","article-title":"COVID-19 Illness in Native and Immunosuppressed States: A Clinical\u2013Therapeutic Staging Proposal","volume":"39","author":"Siddiqi","year":"2020","journal-title":"J. Hear. Lung Transplant."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/S2213-2600(20)30079-5","article-title":"Clinical Course and Outcomes of Critically Ill Patients with SARS-CoV-2 Pneumonia in Wuhan, China: A Single-Centered, Retrospective, Observational Study","volume":"8","author":"Yang","year":"2020","journal-title":"Lancet Respir."},{"key":"ref_17","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 RetrospectiveCohort Study","volume":"395","author":"Zhou","year":"2020","journal-title":"Lancet"},{"key":"ref_18","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_19","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1016\/j.chom.2020.04.009","article-title":"Complex Immune Dysregulation in COVID-19 Patients with Severe Respiratory Failure","volume":"27","author":"Netea","year":"2020","journal-title":"Cell Host Microbe"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1093\/cid\/ciaa248","article-title":"Dysregulation of Immune Response in Patients with COVID-19 in Wuhan, China. Oxford Academic","volume":"71","author":"Qin","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.cyto.2018.01.007","article-title":"Simultaneous Presence of Hypercoagulation and Increased Clot Lysis Time due to IL-1\u03b2, IL-6 and IL-8","volume":"110","author":"Bester","year":"2018","journal-title":"Cytokine"},{"key":"ref_22","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_23","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1111\/jth.14817","article-title":"Anticoagulant Treatment is Associated with Decreased Mortality in Severe Coronavirus Disease 2019 Patients with Coagulopathy","volume":"18","author":"Tang","year":"2020","journal-title":"J. Thromb. Haemost."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2060","DOI":"10.1111\/jth.14860","article-title":"ISTH Interim Guidance on Recognition and Management of Coagulopathy in COVID-19: A Comment","volume":"18","author":"Barrett","year":"2020","journal-title":"J. Thromb. Haemost."},{"key":"ref_25","unstructured":"Kreuziger, L., Lee, A., Garcia, D., Cuker, A., Cushman, M., DeSancho, M., and Connors, J.M. (2021, April 30). COVID-19 and VTE\/Anticoagulation: Frequently Asked Questions American Society of Hematology. Available online: https:\/\/www.hematology.org\/covid-19\/covid-19-and-vte-anticoagulation."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Shi, C., Wang, C., Wang, H., Yang, C., Cai, F., Zeng, F., Cheng, F., Liu, Y., Zhou, T., and Deng, B. (2020). The potential of Low Molecular Weight Heparin to Mitigate Cytokine Storm in Severe COVID-19 Patients: A Retrospective Clinical Study. Medrxiv.","DOI":"10.1101\/2020.03.28.20046144"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1001\/jamainternmed.2020.0994","article-title":"Risk Factors Associated with Acute Respiratory Distress Syndrome and Death in Patients with Coronavirus Disease 2019 Pneumonia in Wuhan, China","volume":"180","author":"Wu","year":"2020","journal-title":"JAMA Intern. Med."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/10\/10\/1214\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:09:54Z","timestamp":1760166594000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/10\/10\/1214"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,6]]},"references-count":27,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2021,10]]}},"alternative-id":["antibiotics10101214"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics10101214","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,6]]}}}