Association Between SARS-CoV-2 Variants and Frequency of Acute Symptoms: Analysis of a Multi-institutional Prospective Cohort Study-December 20, 2020-June 20, 2022

Background: While prior work examining severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern focused on hospitalization and death, less is known about differences in clinical presentation. We compared the prevalence of acute symptoms across pre-Delta, Delta, and Omicron. Methods: We conducted an analysis of the Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE), a cohort study enrolling symptomatic SARS-CoV-2-positive participants. We determined the association between the pre-Delta, Delta, and Omicron time periods and the prevalence of 21 coronavirus disease 2019 (COVID-19) acute symptoms. Results: We enrolled 4113 participants from December 2020 to June 2022. Pre-Delta vs Delta vs Omicron participants had increasing sore throat (40.9%, 54.6%, 70.6%; P <. 001), cough (50.9%, 63.3%, 66.7%; P <. 001), and runny noses (48.9%, 71.3%, 72.9%; P <. 001). We observed reductions during Omicron in chest pain (31.1%, 24.2%, 20.9%; P <. 001), shortness of breath (42.7%, 29.5%, 27.5%; P <. 001), loss of taste (47.1%, 61.8%, 19.2%; P <. 001), and loss of smell (47.5%, 55.6%, 20.0%; P <. 001). After adjustment, those infected during Omicron had significantly higher odds of sore throat vs pre-Delta (odds ratio [OR], 2.76; 95% CI, 2.26-3.35) and Delta (OR, 1.96; 95% CI, 1.69-2.28). Conclusions: Participants infected during Omicron were more likely to report symptoms of common respiratory viruses, such as sore throat, and less likely to report loss of smell and taste. Trial registration: NCT04610515.