ABSTRACT
BACKGROUND: COVID-19 vaccines have lessened the effects of the ongoing pandemic. Those vaccinated are less likely to be hospitalized than unvaccinated and, if hospitalized, have better outcomes. The literature is less developed on the effect of vaccination on disease burden and symptomatology in outpatient settings. We compared the symptom severity from SARS-CoV-2 infection among unvaccinated with those vaccinated within 6 months. We hypothesized that vaccinated individuals will have less symptom burden than unvaccinated. METHODS: We compared the proportion of COVID-19 symptoms at baseline from participants enrolled in the COVID-OUT trial, an outpatient treatment trial of SARS-CoV-2 infection. Adults aged 30-85 with a body mass index >= 25kg/m2 were eligible within 3 days of a positive COVID-19 test;symptoms not required but must be <7 days if present. 413 patients were enrolled through September 12, 2021. Of those, only 124 unvaccinated and 68 vaccinated within 6 months of enrollment provided baseline symptom data. We compared unvaccinated with those vaccinated using Fisher's Exact tests. We computed a total symptom score for each participant reflecting symptom severity and total number of symptoms, assigning numeric values to each grade of symptom severity (mild, moderate, severe), with more points given for higher severity. Treating the total symptom score as continuous, we fit a linear regression model to assess the association between total symptom score and vaccination status. RESULTS: A larger proportion of unvaccinated versus vaccinated reported chills/shivering (19% vs. 6%;p=0.01), diarrhea in the last 24 h (19% vs. 3%;p<0.01), feeling hot or feverish (30% vs. 6%;p<0.01), body aches (55% vs. 26%;p<0.01), and nausea (19% vs. 6%;p=0.02). A larger proportion of vaccinated versus unvaccinated had a stuffy/runny nose (56% vs. 35%;p<0.01). There was no significant difference in cough, headache, loss of smell or taste, fatigue, shortness of breath, difficulty breathing, sore throat, or vomiting between groups. The mean total symptom score for unvaccinated participants was 13.6 (95% CI: (12.4, 14.8)), significantly larger than the vaccinated average score of 11.2 (95% CI: (9.5, 12.8)) (p = 0.02). CONCLUSIONS: There appears to be an association between vaccination and symptom type and severity from COVID-19. Unvaccinated individuals reported more systemic symptoms (fever, chills, and diarrhea);Vaccinated reported more mucosal symptoms (runny nose). This difference could be due to differing IgG and IgA responses to vaccination and decline over time. Although vaccination was associated with a significantly lower total symptom score than those unvaccinated, the small difference may not track with functional outcomes such as return to work.