{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T23:09:02Z","timestamp":1778627342199,"version":"3.51.4"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2021,8,3]],"date-time":"2021-08-03T00:00:00Z","timestamp":1627948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Introduction<\/jats:title>\n<jats:p>Recently, several single center studies have suggested a protective effect of the influenza vaccine against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This study utilizes a continuously updated Electronic Medical Record (EMR) network to assess the possible benefits of influenza vaccination mitigating critical adverse outcomes in SARS-CoV-2 positive patients from 56 healthcare organizations (HCOs).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>The de-identified records of 73,346,583 patients were retrospectively screened. Two cohorts of 37,377 patients, having either received or not received influenza vaccination six months\u2013two weeks prior to SARS-CoV-2 positive diagnosis, were created using Common Procedural Terminology (CPT) and logical observation identifiers names and codes (LOINC) codes. Adverse outcomes within 30, 60, 90, and 120 days of positive SARS-CoV-2 diagnosis were compared between cohorts. Outcomes were assessed with stringent propensity score matching including age, race, ethnicity, gender, hypertension, diabetes, hyperlipidemia, chronic obstructive pulmonary disease (COPD), obesity, heart disease, and lifestyle habits such as smoking.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>SARS-CoV-2-positive patients who received the influenza vaccine experienced decreased sepsis (p&lt;0.01, Risk Ratio: 1.361\u20131.450, 95% CI:1.123\u20131.699, NNT:286) and stroke (p&lt;0.02, RR: 1.451\u20131.580, 95% CI:1.075\u20132.034, NNT:625) across all time points. ICU admissions were lower in SARS-CoV-2-positive patients receiving the influenza vaccine at 30, 90, and 120 days (p&lt;0.03, RR: 1.174\u20131.200, 95% CI:1.003\u20131.385, NNT:435), while approaching significance at 60 days (p = 0.0509, RR: 1.156, 95% CI:0.999\u20131.338). Patients who received the influenza vaccine experienced fewer DVTs 60\u2013120 days after positive SARS-CoV-2 diagnosis (p&lt;0.02, RR:1.41\u20131.530, 95% CI:1.082\u20132.076, NNT:1000) and experienced fewer emergency department (ED) visits 90\u2013120 days post SARS-CoV-2-positive diagnosis (p&lt;0.01, RR:1.204\u20131.580, 95% CI: 1.050\u20131.476, NNT:176).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Our analysis outlines the potential protective effect of influenza vaccination in SARS-CoV-2-positive patients against adverse outcomes within 30, 60, 90, and 120 days of a positive diagnosis. Significant findings favoring influenza vaccination mitigating the risks of sepsis, stroke, deep vein thrombosis (DVT), emergency department (ED) &amp; Intensive Care Unit (ICU) admissions suggest a potential protective effect that could benefit populations without readily available access to SARS-CoV-2 vaccination. Thus further investigation with future prospective studies is warranted.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0255541","type":"journal-article","created":{"date-parts":[[2021,8,3]],"date-time":"2021-08-03T17:31:13Z","timestamp":1628011873000},"page":"e0255541","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":49,"title":["Examining the potential benefits of the influenza vaccine against SARS-CoV-2: A retrospective cohort analysis of 74,754 patients"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7595-0591","authenticated-orcid":true,"given":"Susan M.","family":"Taghioff","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin R.","family":"Slavin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tripp","family":"Holton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Devinder","family":"Singh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,8,3]]},"reference":[{"key":"pone.0255541.ref001","unstructured":"COVID-19 map\u2014johns Hopkins Coronavirus resource Center. Jhu.edu. Accessed January 29, 2021. https:\/\/coronavirus.jhu.edu\/map.html."},{"key":"pone.0255541.ref002","article-title":"Considerations for diagnostic COVID-19 tests","author":"O Vandenberg","year":"2020","journal-title":"Nat Rev Microbiol"},{"key":"pone.0255541.ref003","unstructured":"TriNetX. Trinetx.com. Published May 18, 2018. Accessed January 29, 2021. https:\/\/www.trinetx.com."},{"key":"pone.0255541.ref004","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1200\/CCI.17.00067","article-title":"Using a federated network of real-world data to optimize clinical trials operations","volume":"2","author":"U Topaloglu","year":"2018","journal-title":"JCO Clin Cancer Inform"},{"issue":"6","key":"pone.0255541.ref005","doi-asserted-by":"crossref","DOI":"10.1053\/j.gastro.2020.08.028","article-title":"Impact of obesity on outcomes of patients with coronavirus disease 2019 in the united states: A multicenter electronic health records network study","volume":"159","author":"S Singh","year":"2020","journal-title":"Gastroenterology"},{"key":"pone.0255541.ref006","article-title":"Endoscopic Utilization and Outcomes of Upper Gastrointestinal Bleeding in COVID-19: A Global Real-World Database Analysis","author":"A Perisetti","year":"2020","journal-title":"SSRN"},{"issue":"2","key":"pone.0255541.ref007","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/S2215-0366(20)30462-4","article-title":"Bidirectional associations between COVID-19 and psychiatric disorder: Retrospective cohort studies of 62 354 COVID-19 cases in the USA","volume":"8","author":"M Taquet","year":"2021","journal-title":"Lancet Psychiatry"},{"key":"pone.0255541.ref008","article-title":"Temporal trends in severe COVID-19 outcomes in patients with rheumatic disease: A cohort study","author":"A Jorge","year":"2020","journal-title":"Lancet Rheumatol"},{"key":"pone.0255541.ref009","article-title":"Influenza vaccination and hospitalizations among COVID-19 infected adults","author":"M-J Yang","journal-title":"Journal of the American Board of Family Medicine"},{"issue":"1","key":"pone.0255541.ref010","doi-asserted-by":"crossref","first-page":"14","DOI":"10.21101\/cejph.a6573","article-title":"Annual influenza vaccination effect on the susceptibility to COVID-19 infection","volume":"29","author":"B Erismis","year":"2021","journal-title":"Cent Eur J Public Health"},{"issue":"2","key":"pone.0255541.ref011","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1007\/s10875-020-00925-0","article-title":"A case-control study of the 2019 influenza vaccine and incidence of COVID-19 among healthcare workers","volume":"41","author":"N Massoudi","year":"2021","journal-title":"J Clin Immunol"},{"key":"pone.0255541.ref012","article-title":"Impact of the influenza vaccine on COVID-19 infection rates and severity","author":"A Conlon","year":"2021","journal-title":"Am J Infect Control"},{"issue":"10","key":"pone.0255541.ref013","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1016\/j.it.2020.08.003","article-title":"Effect of Low-Pathogenic Human Coronavirus-Specific Antibodies on SARS-CoV-2","volume":"41","author":"S Jiang","year":"2020","journal-title":"Trends Immunol"},{"key":"pone.0255541.ref014","doi-asserted-by":"crossref","first-page":"106717","DOI":"10.1016\/j.intimp.2020.106717","article-title":"Potential adjuvants for the development of a SARS-CoV-2 vaccine based on experimental results from similar coronaviruses","volume":"86","author":"T Gupta","year":"2020","journal-title":"Int Immunopharmacol"},{"key":"pone.0255541.ref015","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1146\/annurev-immunol-032712-100001","article-title":"Control of human viral infections by natural killer cells","volume":"31","author":"S Jost","year":"2013","journal-title":"Annu Rev Immunol"},{"key":"pone.0255541.ref016","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.3389\/fimmu.2020.01692","article-title":"The Potential Effect of Novel Coronavirus SARS-CoV-2 on NK Cells; A Perspective on Potential Therapeutic Interventions","volume":"11","author":"A Jewett","year":"2020","journal-title":"Front Immunol"},{"issue":"1","key":"pone.0255541.ref017","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.atherosclerosis.2011.03.019","article-title":"Influenza vaccination promotes stable atherosclerotic plaques in apoE knockout mice","volume":"217","author":"A Bermudez-Fajardo","year":"2011","journal-title":"Atherosclerosis"},{"issue":"15","key":"pone.0255541.ref018","doi-asserted-by":"crossref","first-page":"1777","DOI":"10.1016\/j.jacc.2020.08.028","article-title":"Influenza vaccination to reduce cardiovascular morbidity and mortality in patients with COVID-19: JACC state-of-the-art review","volume":"76","author":"B Behrouzi","year":"2020","journal-title":"J Am Coll Cardiol"},{"issue":"48","key":"pone.0255541.ref019","doi-asserted-by":"crossref","first-page":"6569","DOI":"10.1016\/j.vaccine.2014.07.007","article-title":"Influenza vaccine as prevention for cardiovascular diseases: Possible molecular mechanism","volume":"32","author":"V Veljkovic","year":"2014","journal-title":"Vaccine"},{"key":"pone.0255541.ref020","unstructured":"Cdc.gov. 2021. The Flu Season | CDC. [online] Available at: <https:\/\/www.cdc.gov\/flu\/about\/season\/flu-season.htm> [Accessed 21 April 2021]."},{"key":"pone.0255541.ref021","unstructured":"Tenny S, Hoffman MR. Relative risk. In: StatPearls. Treasure Island (FL): StatPearls Publishing LLC; 2021. NBK430824 [bookaccession]."},{"issue":"6","key":"pone.0255541.ref022","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.vaccine.2014.12.033","article-title":"How and why researchers use the number needed to vaccinate to inform decision making\u2014a systematic review","volume":"33","author":"A Hashim","year":"2015","journal-title":"Vaccine"},{"issue":"5","key":"pone.0255541.ref023","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1007\/s00268-005-7916-8","article-title":"Number needed to treat (or harm)","volume":"29","author":"MR Tramer","year":"2005","journal-title":"World J Surg"},{"key":"pone.0255541.ref024","article-title":"Autonomic dysfunction following COVID-19 infection: An early experience","author":"K Shouman","year":"2021","journal-title":"Clin Auton Res"},{"issue":"2","key":"pone.0255541.ref025","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1002\/jmv.26368","article-title":"Postdischarge symptoms and rehabilitation needs in survivors of COVID-19 infection: A cross-sectional evaluation","volume":"93","author":"SJ Halpin","year":"2021","journal-title":"J Med Virol"},{"key":"pone.0255541.ref026","article-title":"Association between influenza vaccination and severe COVID-19 outcomes at a designated COVID-only hospital in brooklyn","author":"OQ Umasabor-Bubu","year":"2021","journal-title":"Am J Infect Control"},{"issue":"4","key":"pone.0255541.ref027","article-title":"Association between exposure to influenza vaccination and COVID-19 diagnosis and outcomes","volume":"8","author":"P Ragni","year":"2020","journal-title":"Vaccines (Basel)"},{"issue":"4","key":"pone.0255541.ref028","article-title":"Influenza vaccination and health outcomes in COVID-19 patients: A retrospective cohort study","volume":"9","author":"PD Pedote","year":"2021","journal-title":"Vaccines (Basel)"},{"key":"pone.0255541.ref029","article-title":"Influenza vaccination and COVID19 mortality in the USA","author":"C Zanettini","year":"2020","journal-title":"medRxiv"},{"key":"pone.0255541.ref030","doi-asserted-by":"crossref","first-page":"e10112","DOI":"10.7717\/peerj.10112","article-title":"Positive association between COVID-19 deaths and influenza vaccination rates in elderly people worldwide","volume":"8","author":"C Wehenkel","year":"2020","journal-title":"PeerJ"},{"issue":"6","key":"pone.0255541.ref031","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.jnma.2020.11.001","article-title":"The COVID-19 and influenza \"twindemic\": Barriers to influenza vaccination and potential acceptance of SARS-CoV2 vaccination in african americans","volume":"112","author":"KC Ferdinand","year":"2020","journal-title":"J Natl Med Assoc"},{"key":"pone.0255541.ref032","unstructured":"Flu Shot May Shield You From Severe COVID. [online] WebMD. Available at: <https:\/\/www.webmd.com\/lung\/news\/20201102\/get-your-flu-shot-it-might-shield-you-from-severe-covid#1> [Accessed 21 April 2021]."},{"issue":"1","key":"pone.0255541.ref033","doi-asserted-by":"crossref","first-page":"4741","DOI":"10.1038\/s41598-021-83641-y","article-title":"Exploratory analysis of immunization records highlights decreased SARS-CoV-2 rates in individuals with recent non-COVID-19 vaccinations","volume":"11","author":"C Pawlowski","year":"2021","journal-title":"Sci Rep"},{"key":"pone.0255541.ref034","unstructured":"\u2019Shocking imbalance\u2019 of COVID-19 vaccine distribution underscores inequity. Healio. https:\/\/www.healio.com\/news\/infectious-disease\/20210514\/shocking-imbalance-of-covid19-vaccine-distribution-underscores-inequity. Accessed June 18, 2021."},{"issue":"3","key":"pone.0255541.ref035","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15585\/mmwr.rr6703a1","article-title":"Prevention and control of seasonal influenza with vaccines: Recommendations of the Advisory Committee on Immunization Practices-United States, 2018\u201319 influenza season","volume":"67","author":"LA Grohskopf","year":"2018","journal-title":"MMWR Recomm Rep"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0255541","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,3]],"date-time":"2021-08-03T17:31:41Z","timestamp":1628011901000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0255541"}},"subtitle":[],"editor":[{"given":"Corstiaan","family":"den Uil","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2021,8,3]]},"references-count":35,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2021,8,3]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0255541","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,3]]}}}