Early Use of Ibuprofen in Moderate Cases of COVID-19 Might be a Promising Agent to Attenuate the Severity of Disease: A Randomized Controlled Trial

{ 'indexed': {'date-parts': [[2023, 4, 21]], 'date-time': '2023-04-21T06:39:58Z', 'timestamp': 1682059198109}, 'reference-count': 11, 'publisher': 'Bentham Science Publishers Ltd.', 'issue': '1', 'license': [ { 'start': { 'date-parts': [[2023, 4, 19]], 'date-time': '2023-04-19T00:00:00Z', 'timestamp': 1681862400000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/legalcode'}], 'content-domain': { 'domain': ['openanesthesiajournal.com', 'benthamopen.com'], 'crossmark-restriction': True}, 'published-print': {'date-parts': [[2023, 4, 19]]}, 'abstract': '<jats:sec>\n' ' <jats:title>Introduction:</jats:title>\n' ' <jats:p>Critically ill COVID-19 patients undergoing cytokine storm are ' 'believed to have a worse prognosis and increased fatality rate. Ibuprofen is a non-steroidal ' 'anti-inflammatory drug (NSAIDs) that might prove beneficial for the early management of ' 'COVID-19 due to its immunomodulatory effects. This study aimed to assess the efficacy and ' 'safety of the early use of ibuprofen to attenuate the severity of the course of COVID-19 and ' 'improve outcomes in patients diagnosed with a moderate case of COVID-19 disease.</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>Methods:</jats:title>\n' ' <jats:p>This randomized, double-blinded prospective study was conducted from ' 'January, 2022 to May, 2022, which included a total sample size of 180 patients with moderate ' 'cases of COVID-19. The number of patients transferred to intensive care was used as a primary ' 'outcome with a proposed large effect size (0.8), alfa =0.05, and power=0.80, so 90 cases were ' 'included in each group. Secondary outcomes were inflammatory markers: C-Reactive Protein ' '(CRP), serum ferritin, and interleukin-6 (IL-6), duration of hospital stay, and need for ICU ' 'admission.</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>Results:</jats:title>\n' ' <jats:p>One hundred eighty patients with moderate case of COVID-19 disease ' 'were divided in a 1: 1 ratio to receive ibuprofen (IG) or paracetamol (CG). The average age ' 'of the included patients was almost 41 years. Statistically significant differences were ' 'reported between both groups in terms of improvement in cough symptoms and lymphopenia in IG ' 'compared to CG (<jats:italic>p</jats:italic>= 0.034 and <jats:italic>p</jats:italic>= 0.044, ' 'respectively). Regarding secondary outcomes, statistically, significant differences were ' 'reported between the study’s groups in terms of the mean number of patients transferred to ' 'the ICU in IG compared to the CG (<jats:italic>p</jats:italic> =0.0.047) and duration of ' 'hospitalization (<jats:italic>p</jats:italic> =0.013), with no significant differences ' '(<jats:italic>p</jats:italic> &gt; 0.9999) in the occurrence of side effects.</jats:p>\n' ' <jats:p>Concerning the follow-up of the cytokine storm marker, there was a ' 'statistically significant reduction in serum cytokine marker compared to the baseline value ' '(<jats:italic>P</jats:italic> &lt; 0.05) in the same group. No statistically significant ' 'differences were observed when comparing both groups together in terms of serum ferritin ' 'level (<jats:italic>p</jats:italic> =0.570), serum IL-6 level (<jats:italic>p</jats:italic> ' '=0.580), and CRP level (<jats:italic>p</jats:italic> =0.401).</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>Conclusion:</jats:title>\n' ' <jats:p>It can be concluded that early use of ibuprofen as adjuvant therapy ' 'in COVID-19 management is effective and safe to attenuate the severity of diseases and ' 'improve outcomes.</jats:p>\n' ' </jats:sec>\n' ' <jats:sec>\n' ' <jats:title>Trial Registration:</jats:title>\n' ' <jats:p>Project manager for the Pan African Clinical Trial Registry ' 'PACTR202202880140319. Registered 9<jats:sup>th</jats:sup> February, 2022 - Retrospectively ' 'registered, (https://pactr.samrc.ac.za/)</jats:p>\n' ' </jats:sec>', 'DOI': '10.2174/25896458-v17-e230403-2022-26', 'type': 'journal-article', 'created': {'date-parts': [[2023, 4, 20]], 'date-time': '2023-04-20T04:07:33Z', 'timestamp': 1681963653000}, 'update-policy': 'http://dx.doi.org/10.2174/crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Early Use of Ibuprofen in Moderate Cases of COVID-19 Might be a Promising Agent to Attenuate the ' 'Severity of Disease: A Randomized Controlled Trial', 'prefix': '10.2174', 'volume': '17', 'author': [ {'given': 'Amr', 'family': 'Sobhy', 'sequence': 'first', 'affiliation': []}, {'given': 'Lobna A.', 'family': 'Saleh', 'sequence': 'additional', 'affiliation': []}, {'given': 'Marwa E.l', 'family': 'AbdelAtty', 'sequence': 'additional', 'affiliation': []}, {'given': 'Marwa E.l', 'family': 'AbdelAtty', 'sequence': 'additional', 'affiliation': []}, {'given': 'Sameh A.', 'family': 'Refaat', 'sequence': 'additional', 'affiliation': []}, {'given': 'Mohammed', 'family': 'Kamal', 'sequence': 'additional', 'affiliation': []}], 'member': '965', 'reference': [ { 'key': 'ref1', 'doi-asserted-by': 'publisher', 'unstructured': 'Mirzaei R, Karampoor S, Sholeh M, Moradi P, Ranjbar R, Ghasemi F. \n' ' A contemporary review on pathogenesis and immunity ' 'of COVID-19 infection. \n' ' Mol Biol Rep \n' ' 2020; \n' ' 47\n' ' (7)\n' ' : 5365-76.', 'DOI': '10.1007/s11033-020-05621-1'}, { 'key': 'ref2', 'doi-asserted-by': 'crossref', 'unstructured': 'Bhaskar S, Sinha A, Banach M, Mittoo S, Weissert R, Kass JS. \n' ' Cytokine storm in COVID-19—immunopathological ' 'mechanisms, clinical considerations, and therapeutic approaches: The ' 'REPROGRAM Consortium Position Paper. \n' ' Front Immunol \n' ' 2020; \n' ' 11\n' ' : 1648.', 'DOI': '10.3389/fimmu.2020.01648'}, { 'key': 'ref3', 'doi-asserted-by': 'publisher', 'unstructured': 'Kelleni MT. \n' ' Early use of non-steroidal anti-inflammatory drugs ' 'in COVID-19 might reverse pathogenesis, prevent complications and ' 'improve clinical outcomes. \n' ' Biomed Pharmacother \n' ' 2021; \n' ' 133\n' ' : 110982.', 'DOI': '10.1016/j.biopha.2020.110982'}, { 'key': 'ref4', 'unstructured': 'Available from: ' 'https://hiph.alexu.edu.eg/images/egyptian_national_guidelines_covid-19.pdf'}, { 'key': 'ref5', 'unstructured': 'Fisman EZ, Shapira I, Motro M, Pines A, Tenenbaum A. \n' ' The combined cough frequency/severity scoring: A new ' 'approach to cough evaluation in clinical settings. \n' ' J Med \n' ' 2001; \n' ' 32\n' ' (3-4)\n' ' : 181-7.'}, { 'key': 'ref6', 'doi-asserted-by': 'publisher', 'unstructured': 'Lu L, Zhang H, Zhan M, et al. \n' ' Preventing mortality in COVID-19 patients: Which ' 'cytokine to target in a raging storm? \n' ' Front Cell Dev Biol \n' ' 2020; \n' ' 8\n' ' : 677.', 'DOI': '10.3389/fcell.2020.00677'}, { 'key': 'ref7', 'doi-asserted-by': 'publisher', 'unstructured': 'Kelleni MT. \n' ' Nitazoxanide/azithromycin combination for COVID-19: ' 'A suggested new protocol for early management. \n' ' Pharmacol Res \n' ' 2020; \n' ' 157\n' ' (July)\n' ' : 104874.', 'DOI': '10.1016/j.phrs.2020.104874'}, { 'key': 'ref8', 'doi-asserted-by': 'publisher', 'unstructured': 'Qin C, Zhou L, Hu Z, et al. \n' ' Dysregulation of immune response in patients with ' 'COVID-19 in Wuhan, China. \n' ' Clin Infect Dis \n' ' 2020; \n' ' 71\n' ' (15)\n' ' : 762-8.', 'DOI': '10.1093/cid/ciaa248'}, { 'key': 'ref9', 'doi-asserted-by': 'publisher', 'unstructured': 'Ramaswamy A, Bhargava P, Panda P, Ostwal V. \n' ' Repurposing valproate to prevent acute respiratory ' 'distress syndrome/acute lung injury in COVID-19: A review of ' 'immunomodulatory action. \n' ' Cancer Research, Statistics, and Treatment \n' ' 2020; \n' ' 3\n' ' (5)\n' ' : 65.', 'DOI': '10.4103/CRST.CRST_156_20'}, { 'key': 'ref10', 'doi-asserted-by': 'crossref', 'unstructured': 'Hashimoto K, Graham BS, Geraci MW, et al. \n' ' Signaling through the prostaglandin I2 receptor IP ' 'protects against respiratory syncytial virus-induced illness. \n' ' J Virol \n' ' 2004; \n' ' 78\n' ' (19)\n' ' : 10303-9.', 'DOI': '10.1128/JVI.78.19.10303-10309.2004'}, { 'key': 'ref11', 'doi-asserted-by': 'publisher', 'unstructured': 'Thomas M. \n' ' Non-steroidal anti-inflammatory drug use and ' 'outcomes of COVID-19 in the ISARIC Clinical Characterisation Protocol UK ' 'cohort: A matched, prospective cohort study. \n' ' Lancet Rheumatol \n' ' 2021; \n' ' 3\n' ' (7)\n' ' : 498-506.', 'DOI': '10.1016/S2665-9913(21)00104-1'}], 'container-title': 'The Open Anesthesia Journal', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://openanesthesiajournal.com/contents/volumes/V17/e258964582303020/e258964582303020.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://openanesthesiajournal.com/contents/volumes/V17/e258964582303020/e258964582303020.xml', 'content-type': 'application/xml', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://openanesthesiajournal.com/contents/volumes/V17/e258964582303020/e258964582303020.pdf', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 4, 20]], 'date-time': '2023-04-20T04:07:39Z', 'timestamp': 1681963659000}, 'score': 1, 'resource': {'primary': {'URL': 'https://openanesthesiajournal.com/VOLUME/17/ELOCATOR/e258964582303020/'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2023, 4, 19]]}, 'references-count': 11, 'journal-issue': {'issue': '1', 'published-print': {'date-parts': [[2023, 4, 19]]}}, 'URL': 'http://dx.doi.org/10.2174/25896458-v17-e230403-2022-26', 'relation': {}, 'ISSN': ['2589-6458'], 'subject': ['Anesthesiology and Pain Medicine'], 'container-title-short': 'TOATJ', 'published': {'date-parts': [[2023, 4, 19]]}, 'assertion': [ { 'value': 'Peer Reviewed', 'order': 0, 'name': 'review_status', 'label': 'Review Status', 'group': {'name': 'peer_review_details', 'label': 'Peer Review Details'}}, { 'value': 'Single blind', 'order': 1, 'name': 'review_process', 'label': 'Review Process', 'group': {'name': 'peer_review_details', 'label': 'Peer Review Details'}}, { 'value': 'Checked with iThenticate', 'order': 0, 'name': 'screening_status', 'label': 'Screening Status', 'group': {'name': 'plagiarism_screening', 'label': 'Plagiarism Screening'}}, { 'value': '2022-10-24', 'order': 0, 'name': 'received', 'label': 'Received', 'group': {'name': 'publication_history', 'label': 'Publication History'}}, { 'value': '2023-1-26', 'order': 1, 'name': 'revised', 'label': 'Revised', 'group': {'name': 'publication_history', 'label': 'Publication History'}}, { 'value': '2023-1-30', 'order': 2, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'publication_history', 'label': 'Publication History'}}, { 'value': '2023-04-19', 'order': 3, 'name': 'published', 'label': 'Published', 'group': {'name': 'publication_history', 'label': 'Publication History'}}]}