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
Authors: Wang Ralph C , Gottlieb Michael , Montoy Juan Carlos C , Rodriguez Robert M , Yu Huihui , Spatz Erica S , Chandler Christopher W , Elmore Joann G , Hannikainen Paavali A , Chang Anna Marie , Hill Mandy , Huebinger Ryan M , Idris Ahamed H , Koo Katherine , Li Shu-Xia , McDonald Samuel , Nichol Graham , O’Laughlin Kelli N , Plumb Ian D , Santangelo Michelle , Saydah Sharon , Stephens Kari A , Venkatesh Arjun K , Weinstein Robert A ,   Innovative Support for Patients with SARS-CoV-2 Infections Registry (INSPIRE) Group, Weinstein Robert A , Gottlieb Michael , Santangelo Michelle , Koo Katherine , Derden Antonia , Gottlieb Michael , Gatling Kristyn , Guzman Diego , Yang Geoffrey , Kaadan Marshall , Hassaballa Minna , Jerger Ryan , Ahmed Zohaib , Choi Michael , Venkatesh Arjun , Spatz Erica , Lin Zhenqiu , Li Shu-Xia , Yu Huihui , Liu Mengni , Venkatesh Arjun , Spatz Erica , Ulrich Andrew , Kinsman Jeremiah , Dorney Jocelyn , Pierce Senyte , Puente Xavier , Nichol Graham , Stephens Kari , Anderson Jill , Morse Dana , Adams Karen , Maat Zenoura , Stober Tracy , O’Laughlin Kelli N , Gentile Nikki , Geyer Rachel E , Willis Michael , Ruiz Luis , Malone Kerry , Park Jasmine , Rising Kristin , Kean Efrat , Kelly Morgan , Schaeffer Kevin , Hannikainen Paavali , Shughart Lindsey , Shughart Hailey , Renzi Nicole , Amadio Grace , Grau Dylan , Watts Phillip , Cheng David , Miao Jessica , Shutty Carly , Charlton Alex , Hill Mandy , Site Ryan Huebinger , Chavez Summer , Kane Arun , Nikonowicz Peter , Idris Ahamed H , McDonald Samuel , Gallegos David , Martin Riley , Elmore Joann , Wisk Lauren , L’Hommedieu Michelle , Chandler Chris , Eguchi Megan , Roldan Kate Diaz , Villegas Nicole , Moreno Raul , Rodriguez Robert , Wang Ralph C , Montoy Juan Carlos , Kemball Robin , Chan Virginia , Chavez Cecilia Lara , Wong Angela , Arreguin Mireya , Plumb Ian D , Hall Aron J , Saydah Sharon , Briggs-Hagen Melissa 
Published: May 2023

Abstract

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 &lt; .001), cough (50.9%, 63.3%, 66.7%; P &lt; .001), and runny noses (48.9%, 71.3%, 72.9%; P &lt; .001). We observed reductions during Omicron in chest pain (31.1%, 24.2%, 20.9%; P &lt; .001), shortness of breath (42.7%, 29.5%, 27.5%; P &lt; .001), loss of taste (47.1%, 61.8%, 19.2%; P &lt; .001), and loss of smell (47.5%, 55.6%, 20.0%; P &lt; .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.