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Objective: To determine the effect of SARS-CoV-2 variants on non-respiratory features of COVID-19 in vaccinated and not fully vaccinated patients using a University of California database., Methods: A longitudinal retrospective review of medical records (n = 63,454) from 1/1/2020-4/26/2022 using the UCCORDS database was performed to compare non-respiratory features, vaccination status, and mortality between variants. Chi-square tests were used to study the relationship between categorical variables using a contingency matrix., Results: Fever was the most common feature across all variants. Fever was significantly higher in not fully vaccinated during the Delta and Omicron waves (p = 0.001; p = 0.001). Cardiac features were statistically higher in not fully vaccinated during Omicron; tachycardia was only a feature of not fully vaccinated during Delta and Omicron; diabetes and GI reflux were features of all variants regardless of vaccine status. Odds of death were significantly increased among those not fully vaccinated in the Delta and Omicron variants (Delta OR: 1.64, p = 0.052; Omicron OR: 1.96, p < 0.01). Vaccination was associated with a decrease in the frequency of non-respiratory features., Conclusions: Risk of non-respiratory features of COVID-19 is statistically higher in those not fully vaccinated across all variants. Risk of death and correlation with vaccination status varied., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)