ABSTRACT
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 [≥]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 ([≤]28 days post-onset) and post-acute ([≥]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 ([≥]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.
ABSTRACT
Determinants of protective immunity against SARS-CoV-2 infection require the development of well-standardized, reproducible antibody assays to be utilized in concert with clinical trials to establish correlates of risk and protection. This need has led to the appearance of a variety of neutralization assays used by different laboratories and companies. Using plasma samples from COVID-19 convalescent individuals with mild-to-moderate disease from a localized outbreak in a single region of the western US, we compared three platforms for SARS-CoV-2 neutralization: assay with live SARS-CoV-2, pseudovirus assay utilizing lentiviral (LV) and vesicular stomatitis virus (VSV) packaging, and a surrogate ELISA test. Vero, Vero E6, HEK293T cells expressing human angiotensin converting enzyme 2 (hACE2), and TZM-bl cells expressing hACE2 and transmembrane serine protease 2 (TMPRSS2) were evaluated. Live-virus and LV-pseudovirus assay with HEK293T cells showed similar geometric mean titers (GMTs) ranging 141-178, but VSV-pseudovirus assay yielded significantly higher GMT (310 95%CI 211-454; p < 0.001). Fifty percent neutralizing dilution (ND50) titers from live-virus and all pseudovirus assay readouts were highly correlated (Pearson r = 0.81-0.89). ND50 titers positively correlated with plasma concentration of IgG against SARS-CoV-2 spike and receptor binding domain (RBD) (r = 0.63-0.89), but moderately correlated with nucleoprotein IgG (r = 0.46-0.73). There was a moderate positive correlation between age and spike (Spearmans rho=0.37, p=0.02), RBD (rho=0.39, p=0.013) and nucleoprotein IgG (rho=0.45, p=0.003). ND80 showed stronger correlation with age than ND50 (ND80 rho=0.51 (p=0.001), ND50 rho=0.28 (p=0.075)). Our data demonstrate high concordance between cell-based assays with live and pseudotyped virions.
ABSTRACT
Community-level seroprevalence surveys are needed to determine the proportion of the population with previous SARS-CoV-2 infection, a necessary component of COVID-19 disease surveillance. In May, 2020, we conducted a cross-sectional seroprevalence study of IgG antibodies for nucleocapsid of SARS-CoV-2 among the residents of Blaine County, Idaho, a ski resort community with high COVID-19 attack rates in late March and Early April (2.9% for ages 18 and older). Participants were selected from volunteers who registered via a secure web link, using prestratification weighting to the population distribution by age and gender within each ZIP Code. Participants completed a survey reporting their demographics and symptoms; 88% of volunteers who were invited to participate completed data collection survey and had 10 ml of blood drawn. Serology was completed via the Abbott Architect SARS-CoV-2 IgG immunoassay. Primary analyses estimated seroprevalence and 95% credible intervals (CI) using a hierarchical Bayesian framework to account for diagnostic uncertainty. Stratified models were run by age, sex, ZIP Code, ethnicity, employment status, and a priori participant-reported COVID-19 status. Sensitivity analyses to estimate seroprevalence included base models with post-stratification for ethnicity, age, and sex, with or without adjustment for multi-participant households. IgG antibodies to the virus that causes COVID-19 were found among 22.7% (95% CI: 20.1%, 25.5%) of residents of Blaine County. Higher levels of antibodies were found among residents of the City of Ketchum 34.8% (95% CI 29.3%, 40.5%), compared to Hailey 16.8% (95%CI 13.7%, 20.3%) and Sun Valley 19.4% (95% 11.8%, 28.4%). People who self-identified as not believing they had COVID-19 had the lowest prevalence 4.8% (95% CI 2.3%, 8.2%). The range of seroprevalence after correction for potential selection bias was 21.9% to 24.2%. This study suggests more than 80% of SARS-CoV-2 infections were not reported. Although Blaine County had high levels of SARS-CoV-2 infection, the community is not yet near the herd immunity threshold.
