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

Abstract Background While prior work examining 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 INSPIRE Registry, a cohort study enrolling symptomatic SARS-CoV-2 positive participants. We determined the association between pre-Delta, Delta, and Omicron time periods and the prevalence of 21 COVID-19 acute symptoms. Results We enrolled 4,113 participants from December 2020 – 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: 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.