Seroincidence of SARS-CoV-2 infection prior to and during the rollout of vaccines in a community-based prospective cohort of U.S. adults
Authors: Nash Denis , Srivastava Avantika , Shen Jenny , Penrose Kate , Kulkarni Sarah Gorrell , Zimba Rebecca , You William , Berry Amanda , Mirzayi Chloe , Maroko Andrew , Parcesepe Angela M. , Grov Christian , Robertson McKaylee M. 
Published: October 2023

LONG ABSTRACTBackgroundInfectious disease surveillance systems, which largely rely on diagnosed cases, underestimate the true incidence of SARS-CoV-2 infection, due to under-ascertainment and underreporting. We used repeat serologic testing to measure N-protein seroconversion in a well-characterized cohort of U.S. adults with no serologic evidence of SARS-CoV-2 infection to estimate the incidence of SARS-CoV-2 infection and characterize risk factors, with comparisons before and after the start of the SARS-CoV-2 vaccine and variant eras.MethodsWe assessed the incidence rate of infection and risk factors in two sub-groups (cohorts) that were SARS-CoV-2 N-protein seronegative at the start of each follow-up period: 1) the pre-vaccine/wild-type era cohort (n=3,421), followed from April to November 2020; and 2) the vaccine/variant era cohort (n=2,735), followed from November 2020 to June 2022. Both cohorts underwent repeat serologic testing with an assay for antibodies to the SARS-CoV-2 N protein (Bio-Rad Platelia SARS-CoV-2 total Ab). We estimated crude incidence and sociodemographic/epidemiologic risk factors in both cohorts. We used multivariate Poisson models to compare the risk of SARS-CoV-2 infection in the pre-vaccine/wild-type era cohort (referent group) to that in the vaccine/variant era cohort, within strata of vaccination status and epidemiologic risk factors (essential worker status, child in the household, case in the household, social distancing).FindingsIn the pre-vaccine/wild-type era cohort, only 18 of the 3,421 participants (0.53%) had>1 vaccine dose by the end of follow-up, compared with 2,497/2,735 (91.3%) in the vaccine/variant era cohort. We observed 323 and 815 seroconversions in the pre-vaccine/wild-type era and the vaccine/variant era and cohorts, respectively, with corresponding incidence rates of 9.6 (95% CI: 8.3-11.5) and 25.7 (95% CI: 24.2-27.3) per 100 person-years. Associations of sociodemographic and epidemiologic risk factors with SARS-CoV-2 incidence were largely similar in the pre-vaccine/wild-type and vaccine/variant era cohorts. However, some new epidemiologic risk factors emerged in the vaccine/variant era cohort, including having a child in the household, and never wearing a mask while using public transit. Adjusted incidence rate ratios (aIRR), with the entire pre-vaccine/wild-type era cohort as the referent group, showed markedly higher incidence in the vaccine/variant era cohort, but with more vaccine doses associated with lower incidence: aIRRun/undervaccinated=5.3 (95% CI: 4.2-6.7); aIRRprimaryseriesonly=5.1 (95% CI: 4.2-7.3); aIRRboostedonce=2.5 (95% CI: 2.1-3.0), and aIRRboostedtwice=1.65 (95% CI: 1.3-2.1). These associations were essentially unchanged in risk factor-stratified models.InterpretationIn SARS-CoV-2 N protein seronegative individuals, large increases in incidence and newly emerging epidemiologic risk factors in the vaccine/variant era likely resulted from multiple co-occurring factors, including policy changes, behavior changes, surges in transmission, and changes in SARS-CoV-2 variant properties. While SARS-CoV-2 incidence increased markedly in most groups in the vaccine/variant era, being up to date on vaccines and the use of non-pharmaceutical interventions (NPIs), such as masking and social distancing, remained reliable strategies to mitigate the risk of SARS-CoV-2 infection, even through major surges due to immune evasive variants. Repeat serologic testing in cohort studies is a useful and complementary strategy to characterize SARS-CoV-2 incidence and risk factors.SHORT ABSTRACTThis study used repeat serologic testing to estimate infection rates and risk factors in two overlapping cohorts of SARS-CoV-2 N protein seronegative U.S. adults. One mostly unvaccinated sub-cohort was tracked from April to November 2020 (pre-vaccine/wild-type era, n=3,421), and the other, mostly vaccinated cohort, from November 2020 to June 2022 (vaccine/variant era, n=2,735). Vaccine uptake was from 0.53% and 91.3% in the pre-vaccine and vaccine/variant cohorts, respectively. Corresponding seroconversion rates were 9.6 and 25.7 per 100 person-years. In both cohorts, sociodemographic and epidemiologic risk factors for infection were similar, though new risks emerged in the vaccine/variant era, such as having a child in the household. Despite higher incidence rates in the vaccine/variant cohort, vaccine boosters, masking, and distancing likely reduced infection risk, even through major variant surges. Repeat serologic testing in cohorts is a useful and complementary strategy to characterize incidence and risk factors.FundingThe work was supported by the CUNY Institute for Implementation Science in Population Health, the U.S. National Institutes of Allergy and Infectious Diseases (NIAID), Pfizer, Inc., and the U.S. National Institute of Mental Health (NIMH).