COVID-19 vaccine antibody response is associated with side-effects, chronic health conditions, and vaccine type in a large Northern California cohort (preprint)

As vaccines have become available for COVID-19, it is important to understand factors that may impact response. The objective of this study is to describe vaccine response in a well-characterized Northern California cohort, including differences in side-effects and antibody response by vaccine type, sex, and age, as well as describe responses in subjects with pre-existing health conditions that are known risk factors for more severe COVID-19 infection. From July 2020 to March 2021, ~5,500 adults from the East Bay Area in Northern California were followed as part of a longitudinal cohort study. Comprehensive questionnaire data and biospecimens for COVID-19 antibody testing were collected at multiple time-points. All subjects were at least 18 years of age and members of the East-Bay COVID-19 cohort who answered questionnaires related to vaccination status and side-effects at two time-points. Three vaccines, Moderna (2 doses), Pfizer-BioNTech (2 doses), and Johnson & Johnson (single dose), were examined as exposures. Additionally, pre-existing health conditions were assessed. The main outcomes of interest were anti-SARS-CoV-2 Spike antibody response (measured by S/C ratio in the Ortho VITROS assay) and self-reporting of 11 potential vaccine side effects. When comparing both doses of the Moderna vaccine to respective doses of Pfizer-BioNTech, participants receiving the Moderna vaccine had higher odds of many reported side-effects. The same was true comparing the single-dose Johnson & Johnson vaccine to dose 2 of the Pfizer-BioNTech vaccine. The antibody S/C ratio also increased with each additional side-effect after the second dose. S/C ratios after vaccination were lower in participants aged 65 and older, and higher in females. At all vaccination timepoints, Moderna vaccine recipients had a higher S/C ratio. Individuals who were fully vaccinated with Pfizer-BioNTech had a 72.4% lower S/C ratio compared to those who were fully vaccinated with Moderna. Subjects with asthma, diabetes, and cardiovascular disease all demonstrated more than a 20% decrease in S/C ratio. In support of previous findings, we show that antibody response to the Moderna vaccine is higher than the Pfizer-BioNTech vaccine. We also observed that antibody response was associated with side-effects, and participants with a history of asthma, diabetes, and cardiovascular disease had lower antibody responses. This information is important to consider as further vaccines are recommended.

Impact of individual-level characteristics and transmission mitigation behaviors on SARS-CoV-2 infection and seroprevalence in a large Northern California Bay Area cohort (preprint)

Comprehensive data on transmission mitigation behaviors and SARS-CoV-2 infection and serostatus are needed from large, community-based cohorts to identify SARS-CoV-2 risk factors and impact of public health measures. From July 2020 to March 2021, {approx}5,500 adults from the East Bay Area, California were followed over three data collection rounds. We estimated the prevalence of antibodies from SARS-CoV-2 infection and COVID-19 vaccination, and self-reported COVID-19 test positivity. Population-adjusted SARS-CoV-2 seroprevalence was low, increasing from 1.03% (95% CI: 0.50-1.96) in Round 1 (July-September 2020), to 1.37% (95% CI: 0.75-2.39) in Round 2 (October-December 2020), to 2.18% (95% CI: 1.48-3.17) in Round 3 (February-March 2021). Population-adjusted seroprevalence of COVID-19 vaccination was 21.64% (95% CI: 19.20-24.34) in Round 3. Despite >99% of participants reporting wearing masks, non-Whites, lower-income, and lower-educated individuals had the highest SARS-CoV-2 seroprevalence and lowest vaccination seroprevalence. Our results demonstrate that more effective policies are needed to address these disparities and inequities.

Development and Implementation of Dried Blood Spot-based COVID-19 Serological Assays for Epidemiologic Studies (preprint)

Serological surveillance studies of infectious diseases provide population-level estimates of infection and antibody prevalence, generating crucial insight into population-level immunity, risk factors leading to infection, and effectiveness of public health measures. These studies traditionally rely on detection of pathogen-specific antibodies in samples derived from venipuncture, an expensive and logistically challenging aspect of serological surveillance. During the COVID-19 pandemic, guidelines implemented to prevent the spread of SARS-CoV-2 infection made collection of venous blood logistically difficult at a time when SARS-CoV-2 serosurveillance was urgently needed. Dried blood spots (DBS) have generated interest as an alternative to venous blood for SARS-CoV-2 serological applications due to their stability, low cost, and ease of collection; DBS samples can be self-generated via fingerprick by community members and mailed at ambient temperatures. Here, we detail the development of four DBS-based SARS-CoV-2 serological methods and demonstrate their implementation in a large serological survey of community members from 12 cities in the East Bay region of the San Francisco metropolitan area using at-home DBS collection. We find that DBS perform similarly to plasma/serum in enzyme-linked immunosorbent assays and commercial SARS-CoV-2 serological assays. In addition, we show that DBS samples can reliably detect antibody responses months post-infection and track antibody kinetics after vaccination. Implementation of DBS enabled collection of valuable serological data from our study population to investigate changes in seroprevalence over an eight-month period. Our work makes a strong argument for the implementation of DBS in serological studies, not just for SARS-CoV-2, but any situation where phlebotomy is inaccessible.

Epidemics of chikungunya, Zika, and COVID-19 reveal bias in case-based mapping (preprint)

ABSTRACT Accurate tracing of epidemic spread over space enables effective control measures. We examined three metrics of infection and disease in a pediatric cohort (N ≈ 3,000) over two chikungunya and one Zika epidemic, and in a household cohort (N=1,793) over one COVID-19 epidemic in Managua, Nicaragua. We compared spatial incidence rates (cases/total population), infection risks (infections/total population), and disease risks (cases/infected population). We used generalized additive and mixed-effects models, Kulldorf’s spatial scan statistic, and intracluster correlation coefficients. Across different analyses and all epidemics, incidence rates considerably underestimated infection and disease risks, producing large and spatially non-uniform biases distinct from biases due to incomplete case ascertainment. Infection and disease risks exhibited distinct spatial patterns, and incidence clusters inconsistently identified areas of either risk. While incidence rates are commonly used to infer infection and disease risk in a population, we find that this can induce substantial biases and adversely impact policies to control epidemics. Article summary line Inferring measures of spatial risk from case-only data can substantially bias estimates, thereby weakening and potentially misdirecting measures needed to control an epidemic.

Genomic epidemiology of SARS-CoV-2 transmission lineages in Ecuador (preprint)

Characterisation of SARS-CoV-2 genetic diversity through space and time can reveal trends in virus importation and domestic circulation, and permit the exploration of questions regarding the early transmission dynamics. Here we present a detailed description of SARS-CoV-2 genomic epidemiology in Ecuador, one of the hardest hit countries during the early stages of the COVID-19 pandemic. We generate and analyse 160 whole genome sequences sampled from all provinces of Ecuador in 2020. Molecular clock and phylgeographic analysis of these sequences in the context of global SARS-CoV-2 diversity enable us to identify and characterise individual transmission lineages within Ecuador, explore their spatiotemporal distributions, and consider their introduction and domestic circulation. Our results reveal a pattern of multiple international importations across the country, with apparent differences between key provinces. Transmission lineages were mostly introduced before the implementation of non-pharmaceutical interventions (NPIs), with differential degrees of persistence and national dissemination.