Assessing COVID-19 Vaccine Effectiveness in Observational Studies via Nested Trial Emulation (preprint)

Observational data are often used to estimate real-world effectiveness and durability of coronavirus disease 2019 (COVID-19) vaccines. A sequence of nested trials can be emulated to draw inference from such data while minimizing selection bias, immortal time bias, and confounding. Typically, when nested trial emulation (NTE) is employed, effect estimates are pooled across trials to increase statistical efficiency. However, such pooled estimates may lack a clear interpretation when the treatment effect is heterogeneous across trials. In the context of COVID-19, vaccine effectiveness quite plausibly will vary over calendar time due to newly emerging variants of the virus. This manuscript considers a NTE inverse probability weighted estimator of vaccine effectiveness that may vary over calendar time, time since vaccination, or both. Statistical testing of the trial effect homogeneity assumption is considered. Simulation studies are presented examining the finite-sample performance of these methods under a variety of scenarios. The methods are used to estimate vaccine effectiveness against COVID-19 outcomes using observational data on over 120,000 residents of Abruzzo, Italy during 2021.

Comparison of Capillary Blood Self-Collection using the Tasso-SST Device with Venous Phlebotomy for anti-SARS-CoV-2 Antibody Measurement (preprint)

Measuring seroprevalence over time is a valuable epidemiological tool for improving our understanding of COVID-19 immunity. Due to the large number of collections required for population surveillance as well as concerns about potential infection risk to the collectors, self-collection approaches are being increasingly pursued. To advance this methodology, we collected paired venous and capillary blood samples by routine phlebotomy and Tasso-SST device respectively from 26 participants and measured total immunoglobulin (Ig) and IgG antibodies to the SARS-CoV-2 receptor binding domain (RBD) by enzyme-linked immunosorbent assay (ELISA) on both specimens. Qualitatively, no discrepancies were noted in binary results between Tasso and venipuncture-derived plasma. Furthermore, in vaccinated participants, correlation between Tasso and venous Ig total and IgG specific antibody quantitative levels was high (Total Ig: {rho} ; = 0.72, 95% CI (0.39- 0.90); IgG {rho} ; = 0.85, 95% CI (0.54, 0.96)). Our results support the use of Tasso at-home collection devices for antibody testing.

Social isolation and psychological distress among southern US college students in the era of COVID-19 (preprint)

Objective: To examine the prevalence of psychological distress and its association with social isolation among University of North Carolina Chapel Hill (UNC-CH) students. Methods A cross-sectional survey was emailed to all students in June 2020. Students reported self-isolating none, some, most, or all of the time and were screened for clinically significant symptoms of depression (CSSD). Data were weighted to the UNC-CH population. Results: 7,012 students completed surveys-64% reported self-isolating most or all of the time and 64% reported CSSD. Compared to those self-isolating none of the time, students self-isolating some of the time were 1.78 (95% CI 1.37-2.30) times as likely to report CSSD, and students self-isolating most and all of the time were 2.12 (95% CI 1.64-2.74) and 2.27 (95% CI 1.75-2.94) times as likely to report CSSD, respectively. Conclusions: Universities should prioritize student mental health and prepare support services to mitigate mental health consequences of the pandemic.

A prospective study of asymptomatic SARS-CoV-2 infection among individuals involved in academic research under limited operations during the COVID-19 pandemic (preprint)

Background: Early in the pandemic, transmission risk from asymptomatic infection was unclear making it imperative to monitor infection in workplace settings. Further, data on SARS-CoV-2 seroprevalence within university populations has been limited. Methods: We performed a longitudinal study of University research employees on campus July-December 2020. We conducted questionnaires on COVID-19 risk factors, RT-PCR testing, and SARS-CoV-2 serology using an in-house spike RBD assay, laboratory-based Spike NTD assay, and standard nucleocapsid platform assay. We estimated prevalence and cumulative incidence of seroconversion with 95% confidence intervals using the inverse of the Kaplan-Meier estimator. Results: 910 individuals were included in this analysis. At baseline, 6.2% (95% CI 4.29-8.19) were seropositive using the spike RBD assay; four (0.4%) were seropositive using the nucleocapsid assay, and 44 (4.8%) using the Spike NTD assay. Cumulative incidence was 3.61% (95% CI: 2.04-5.16). Six asymptomatic individuals had positive RT-PCR results. Conclusions: Prevalence and incidence of SARS-CoV-2 infections was low; however differences in target antigens of serological tests provided different estimates. Future research on appropriate methods of serological testing in unvaccinated and vaccinated populations is needed. Frequent RT-PCR testing of asymptomatic individuals is required to detect acute infections, and repeated serosurveys are beneficial for monitoring subclinical infection.

Estimating SARS-CoV-2 Seroprevalence (preprint)

Governments and public health authorities use seroprevalence studies to guide responses to the COVID-19 pandemic. Seroprevalence surveys estimate the proportion of individuals who have detectable SARS-CoV-2 antibodies. However, serologic assays are prone to misclassification error, and non-probability sampling may induce selection bias. In this paper, nonparametric and parametric seroprevalence estimators are considered that address both challenges by leveraging validation data and assuming equal probabilities of sample inclusion within covariate-defined strata. Both estimators are shown to be consistent and asymptotically normal, and consistent variance estimators are derived. Simulation studies are presented comparing the estimators over a range of scenarios. The methods are used to estimate SARS-CoV-2 seroprevalence in New York City, Belgium, and North Carolina.

SARS-CoV-2 seropositivity after infection and antibody response to mRNA-based vaccination (preprint)

The effect of SARS-CoV-2 infection on response to mRNA-based SARS-CoV-2 vaccines is not well-described. We assessed longitudinal SARS-CoV-2-specific antibody responses pre- and post-vaccination among individuals with and without prior infection. The antibody response to the first vaccine dose was almost two-fold higher in individuals who were seropositive before vaccination compared to those who were seronegative, suggesting that prior infection primes the immune response to the first dose of mRNA-based vaccine.