Acute and Post-Acute COVID-19 Outcomes Among Immunologically Naïve Adults During Delta Versus Omicron Waves

II.ImportanceThe U.S. arrival of the Omicron variant led to a rapid increase in SARS-CoV-2 infections. While numerous studies report characteristics of Omicron infections among vaccinated individuals and/or persons with a prior history of infection, comprehensive data describing infections among immunologically naive adults is lacking. ObjectiveTo examine COVID-19 acute and post-acute clinical outcomes among a well-characterized cohort of unvaccinated and previously uninfected adults who contracted SARS-CoV-2 during the Omicron (BA.1/BA.2) surge, and to compare outcomes with infections that occurred during the Delta wave. DesignA prospective cohort undergoing high-resolution symptom and virologic monitoring between June 2021 and September 2022 SettingMultisite recruitment of community-dwelling adults in 8 U.S. states ParticipantsHealthy, unvaccinated adults between 30 to 64 years of age without an immunological history of SARS-CoV-2 who were at high-risk of infection were recruited. Participants were followed for up to 48 weeks, submitting regular COVID-19 symptom surveys and nasal swabs for SARS-CoV-2 PCR testing. Exposure(s)Omicron (BA.1/BA.2 lineages) versus Delta SARS-CoV-2 infection, defined as a positive PCR that occurred during a period when the variant represented [&ge;]50% of circulating SARS-CoV-2 variants in the participants geographic region. Main Outcome(s) and Measure(s)The main outcomes examined were the prevalence and severity of acute ([&le;]28 days post-onset) and post-acute ([&ge;]5 weeks post-onset) symptoms. ResultsAmong 274 immunologically naive participants, 166 (61%) contracted SARS-CoV-2. Of these, 137 (83%) and 29 (17%) infections occurred during the Omicron- and Delta-predominant periods, respectively. Asymptomatic infections occurred among 6.7% (95% CI: 3.1%, 12.3%) of Omicron cases and 0.0% (95% CI: 0.0%, 11.9%) of Delta cases. Healthcare utilization among Omicron cases was 79% (95% CI: 43%, 92%, P =0.001) lower relative to Delta cases. Relative to Delta, Omicron infections also experienced a 56% (95% CI: 26%, 74%, P =0.004) and 79% (95% CI: 54%, 91%, P <0.001) reduction in the risk and rate of post-acute symptoms, respectively. Conclusions and RelevanceThese findings suggest that among previously immunologically naive adults, few Omicron (BA.1/BA.2) and Delta infections are asymptomatic, and relative to Delta, Omicron infections were less likely to seek healthcare and experience post-acute symptoms. KEY POINTSO_ST_ABSQuestionC_ST_ABSWhat are acute and post-acute outcomes among previously uninfected and unvaccinated adults who contracted Omicron (BA.1/BA.2), and how do these compare with Delta infections? FindingsIn this prospective cohort of 274 immunologically naive adults, 166 (61%) contracted SARS-CoV-2, with 9 (5.5%) asymptomatic infections. Compared with Delta, Omicron infections experienced a 79% relative reduction in healthcare utilization, and 56% and 79% relative reductions in the risk and rate of post-acute symptoms ([&ge;]5-weeks), respectively. MeaningThese findings suggest among immunologically naive adults, few infections are asymptomatic, and relative to Delta, Omicron infections have lower likelihoods of severe illness and post-acute symptoms.