{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T21:46:45Z","timestamp":1775771205226,"version":"3.50.1"},"reference-count":7,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,9,17]],"date-time":"2022-09-17T00:00:00Z","timestamp":1663372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Rainwater Charitable Foundation, Parsemus Foundation"},{"DOI":"10.13039\/100016127","name":"Fast Grants","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100016127","id-type":"DOI","asserted-by":"crossref"}]},{"name":"UnitedHealth Group Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,2,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination has decreasing protection from acquiring any infection with emergence of new variants; however, vaccination continues to protect against progression to severe coronavirus disease 2019 (COVID-19). The impact of vaccination status on symptoms over time is less clear.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Within a randomized trial on early outpatient COVID-19 therapy testing metformin, ivermectin, and\/or fluvoxamine, participants recorded symptoms daily for 14 days. Participants were given a paper symptom diary allowing them to circle the severity of 14 symptoms as none (0), mild (1), moderate (2), or severe (3). This is a secondary analysis of clinical trial data on symptom severity over time using generalized estimating equations comparing those unvaccinated, SARS-CoV-2 vaccinated with primary vaccine series only, or vaccine-boosted.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The parent clinical trial prospectively enrolled 1323 participants, of whom 1062 (80%) prospectively recorded some daily symptom data. Of these, 480 (45%) were unvaccinated, 530 (50%) were vaccinated with primary series only, and 52 (5%) vaccine-boosted. Overall symptom severity was least for the vaccine-boosted group and most severe for unvaccinated at baseline and over the 14 days (P &amp;lt; .001). Individual symptoms were least severe in the vaccine-boosted group including cough, chills, fever, nausea, fatigue, myalgia, headache, and diarrhea, as well as smell and taste abnormalities. Results were consistent over Delta and Omicron variant time periods.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>SARS-CoV-2 vaccine-boosted participants had the least severe symptoms during COVID-19, which abated the quickest over time.<\/jats:p>\n                  <jats:p>Clinical Trial Registration. NCT04510194.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/cid\/ciac772","type":"journal-article","created":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T08:45:28Z","timestamp":1663663528000},"page":"e1-e9","source":"Crossref","is-referenced-by-count":15,"title":["Impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccination and Booster on Coronavirus Disease 2019 (COVID-19) Symptom Severity Over Time in the COVID-OUT Trial"],"prefix":"10.1093","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4715-0060","authenticated-orcid":false,"given":"David R","family":"Boulware","sequence":"first","affiliation":[{"name":"Department of Medicine, Medical School, University of Minnesota , Minneapolis, Minnesota , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas A","family":"Murray","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, School of Public Health, University of Minnesota , Minneapolis, Minnesota , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer L","family":"Proper","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, School of Public Health, University of Minnesota , Minneapolis, Minnesota , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher J","family":"Tignanelli","sequence":"additional","affiliation":[{"name":"Department of Surgery, Medical School, University of Minnesota , Minneapolis, Minnesota , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John B","family":"Buse","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, University of North Carolina , Chapel Hill, North Carolina , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M","family":"Liebovitz","sequence":"additional","affiliation":[{"name":"Department of Medicine, Northwestern University Feinberg School of Medicine , Chicago, Illinois , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacinda M","family":"Nicklas","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine, University of Colorado-Anschutz Medical Campus , Aurora, Colorado , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth","family":"Cohen","sequence":"additional","affiliation":[{"name":"UnitedHealth Group, Optum Labs , Minnetonka, Minnesota , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael A","family":"Puskarich","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, School of Medicine, University of Minnesota , Minneapolis, Minnesota , USA"},{"name":"Department of Emergency Medicine, Hennepin County Medical Center , Minneapolis, Minnesota , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hrishikesh K","family":"Belani","sequence":"additional","affiliation":[{"name":"Department of Medicine, Olive View - University of California , Los Angeles, California , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lianne K","family":"Siegel","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, School of Public Health, University of Minnesota , Minneapolis, Minnesota , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nichole R","family":"Klatt","sequence":"additional","affiliation":[{"name":"Department of Surgery, Medical School, University of Minnesota , Minneapolis, Minnesota , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J","family":"Odde","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Minnesota , Minneapolis, Minnesota , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy B","family":"Karger","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota , Minneapolis, Minnesota , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas E","family":"Ingraham","sequence":"additional","affiliation":[{"name":"Department of Medicine, Medical School, University of Minnesota , Minneapolis, Minnesota , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katrina M","family":"Hartman","sequence":"additional","affiliation":[{"name":"Department of Medicine, Medical School, University of Minnesota , Minneapolis, Minnesota , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Via","family":"Rao","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, School of Public Health, University of Minnesota , Minneapolis, Minnesota , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aubrey A","family":"Hagen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Medical School, University of Minnesota , Minneapolis, Minnesota , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barkha","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Medicine, Medical School, University of Minnesota , Minneapolis, Minnesota , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah L","family":"Fenno","sequence":"additional","affiliation":[{"name":"Department of Medicine, Medical School, University of Minnesota , Minneapolis, Minnesota , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nandini","family":"Avula","sequence":"additional","affiliation":[{"name":"Department of Medicine, Medical School, University of Minnesota , Minneapolis, Minnesota , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neha V","family":"Reddy","sequence":"additional","affiliation":[{"name":"Department of Medicine, Medical School, University of Minnesota , Minneapolis, Minnesota , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Spencer M","family":"Erickson","sequence":"additional","affiliation":[{"name":"Department of Medicine, Medical School, University of Minnesota , Minneapolis, Minnesota , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Lindberg","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, School of Public Health, University of Minnesota , Minneapolis, Minnesota , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Regina","family":"Fricton","sequence":"additional","affiliation":[{"name":"Department of Medicine, Northwestern University Feinberg School of Medicine , Chicago, Illinois , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medicine, Northwestern University Feinberg School of Medicine , Chicago, Illinois , 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