{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T06:29:15Z","timestamp":1790404155372,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,11,16]],"date-time":"2019-11-16T00:00:00Z","timestamp":1573862400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004423","name":"World Health Organization","doi-asserted-by":"publisher","award":["2019\/884896"],"award-info":[{"award-number":["2019\/884896"]}],"id":[{"id":"10.13039\/100004423","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Influenza Resp Viruses"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>A range of immunomodulatory therapies have been proposed as adjuncts to conventional antivirals to suppress harmful inflammation during severe influenza infection. We conducted a systematic review to assess available data of the effect of adjunctive non\u2010corticosteroid immunomodulatory therapy and potential adverse effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>We searched MEDLINE, Embase, Web of Science and clinical trial databases for published and unpublished studies, and screened the references of included articles. We included RCTs, quasi\u2010RCTs and observational studies of virologically confirmed influenza infections in hospitalised patients. We did not restrict studies by language of publication, influenza type\/subtype or age of participants. Where possible, we pooled estimates of effect using random\u2010effects meta\u2010analysis models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified 11 eligible studies for inclusion: five studies (4 RCTs and 1 observational; 693 individuals) of passive immune therapy; four studies (3 RCTs and 1 observational; 1120 individuals) of macrolides and\/or non\u2010steroidal anti\u2010inflammatory drugs (NSAIDs), one RCT of mTOR inhibitors (38 individuals), and one RCT of statin therapy (116 individuals). Meta\u2010analysis of RCTs of passive immune therapy indicated no significant reduction in mortality (OR 0.84, 0.37\u20101.90), but better clinical outcomes at Day 7 (OR 1.42, 1.05\u20101.92). There was a significant reduction in mortality associated with macrolides and\/or NSAIDs (OR 0.28; 0.10\u20100.77).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Passive immune therapy is unlikely to offer substantial mortality benefit in treatment of severe seasonal influenza, but may improve clinical outcomes. The effect of other immunomodulatory agents is uncertain, but promising. There is a need for high\u2010quality RCTs with sufficient statistical power to address this evidence gap.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/irv.12699","type":"journal-article","created":{"date-parts":[[2019,11,16]],"date-time":"2019-11-16T03:04:48Z","timestamp":1573873488000},"page":"226-236","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Passive immune therapy and other immunomodulatory agents for the treatment of severe influenza: Systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1463-2298","authenticated-orcid":false,"given":"Vanessa W.","family":"Lim","sequence":"first","affiliation":[{"name":"National Centre for infectious Diseases Singapore City Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8414-7664","authenticated-orcid":false,"given":"Lorainne","family":"Tudor Car","sequence":"additional","affiliation":[{"name":"Lee Kong Chian School of Medicine Nanyang Technological University Singapore City Singapore"},{"name":"School of Public Health Imperial College London London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4978-5825","authenticated-orcid":false,"given":"Yee\u2010Sin","family":"Leo","sequence":"additional","affiliation":[{"name":"National Centre for infectious Diseases Singapore City Singapore"},{"name":"Lee Kong Chian School of Medicine Nanyang Technological University Singapore City Singapore"},{"name":"Saw Swee Hock School of Public Health National University of Singapore Singapore City Singapore"},{"name":"Yong Loo Lin School of Medicine National University of Singapore Singapore City Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9369-5830","authenticated-orcid":false,"given":"Mark I\u2010Cheng","family":"Chen","sequence":"additional","affiliation":[{"name":"National Centre for infectious Diseases Singapore City Singapore"},{"name":"Saw Swee Hock School of Public Health National University of Singapore Singapore City Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1010-2230","authenticated-orcid":false,"given":"Barnaby","family":"Young","sequence":"additional","affiliation":[{"name":"National Centre for infectious Diseases Singapore City Singapore"},{"name":"Lee Kong Chian School of Medicine Nanyang Technological University Singapore City Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,11,16]]},"reference":[{"key":"e_1_2_5_2_1","unstructured":"WHO.Seasonal influenza. 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