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Clinical Trial
. 2023 Feb 8;76(3):e1-e9.
doi: 10.1093/cid/ciac772.

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

David R Boulware  1 , Thomas A Murray  2 , Jennifer L Proper  2 , Christopher J Tignanelli  3 , John B Buse  4 , David M Liebovitz  5 , Jacinda M Nicklas  6 , Kenneth Cohen  7 , Michael A Puskarich  8   9 , Hrishikesh K Belani  10 , Lianne K Siegel  2 , Nichole R Klatt  3 , David J Odde  11 , Amy B Karger  12 , Nicholas E Ingraham  1 , Katrina M Hartman  1 , Via Rao  2 , Aubrey A Hagen  1 , Barkha Patel  1 , Sarah L Fenno  1 , Nandini Avula  1 , Neha V Reddy  1 , Spencer M Erickson  1 , Sarah Lindberg  2 , Regina Fricton  5 , Samuel Lee  5 , Adnin Zaman  6 , Hanna G Saveraid  1 , Walker J Tordsen  9 , Matthew F Pullen  1 , Nancy E Sherwood  13 , Jared D Huling  2 , Carolyn T Bramante  1 ; COVID-OUT study team
Affiliations
Clinical Trial

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

David R Boulware et al. Clin Infect Dis. .

Abstract

Background: 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.

Methods: 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.

Results: 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 < .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.

Conclusions: SARS-CoV-2 vaccine-boosted participants had the least severe symptoms during COVID-19, which abated the quickest over time. Clinical Trial Registration. NCT04510194.

Keywords: COVID-19; SARS-CoV-2; symptoms; vaccine.

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Conflict of interest statement

Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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